WorldWideScience

Sample records for response inhibition planning

  1. The Influence of Planning and Response Inhibition on Cognitive Functioning of Non-Psychotic Unipolar Depressed Suicide Attempters

    Directory of Open Access Journals (Sweden)

    Marco Moniz

    2017-11-01

    Full Text Available Depression is one of the main risk factors for suicide. However, little is known about the intricate relationships among depressive symptomatology in unipolar depression, suicide risk, and the characteristics of executive dysfunction in depressed patients. We compared 20 non-psychotic unipolar depressed suicide attempters to 20 matching depressed non-attempters and to 20 healthy controls to further investigate the possible differences in neuropsychological performance. Depressed subjects were controlled for current suicidal ideation, and their neuropsychological profile was assessed using a range of measures of executive functioning, attention, verbal memory, processing speed, and psychomotor speed. Depressed groups were outperformed by healthy controls. Depressed attempters presented more cognitive impairment than depressed non-attempters on a simple Go/No-go response inhibition task and performed better than non-attempters on the Tower of London planning task. Depressed attempters were clearly distinguished by a deficit in response inhibition (Go/No-go commission errors. The normative planning performance (Tower of London extra moves of the suicide attempters was unexpected, and this unanticipated finding calls for further research. Normative planning may indicate an increased risk of suicidal behavior.

  2. No effects of bilateral tDCS over inferior frontal gyrus on response inhibition and aggression

    NARCIS (Netherlands)

    Dambacher, F.; Schuhmann, T.; Lobbestael, J.; Arntz, A.; Brugman, S.; Sack, A.T.

    2015-01-01

    Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression.

  3. Sleep hygiene behaviours: an application of the theory of planned behaviour and the investigation of perceived autonomy support, past behaviour and response inhibition.

    Science.gov (United States)

    Kor, Kenny; Mullan, Barbara Ann

    2011-09-01

    This study investigated the sleep hygiene behaviour of university students within the framework of the Theory of Planned Behaviour (TPB [Ajzen, I. (1991). The theory of planned behavior. Organizational Behavior and Human Decision Processes, 50, 179-211.]), and examined the predictive validity of additional variables including perceived autonomy support, past behaviour and response inhibition. A total of 257 undergraduate students from an Australian university were administered two online questionnaires at two time points. At time 1, participants completed the TPB questionnaire and the Go/NoGo task as a measure of response inhibition. A week later at time 2, participants completed a questionnaire measuring the performance of sleep hygiene behaviours. Multiple and hierarchical regression analyses showed that the TPB model significantly predicted intention and behaviour. Although intention and perceived behavioural control were statistically significant in predicting behaviour, past behaviour and response inhibition accounted for more variance when added to the TPB model. Subjective norm was found to be the strongest predictor of intention implying the importance of normative influences in sleep hygiene behaviours. Response inhibition was the strongest predictor of behaviour, reinforcing the argument that the performance of health protective behaviours requires self-regulatory ability. Therefore, interventions should be targeted at enhancing self-regulatory capacity.

  4. Response inhibition in motor conversion disorder.

    Science.gov (United States)

    Voon, Valerie; Ekanayake, Vindhya; Wiggs, Edythe; Kranick, Sarah; Ameli, Rezvan; Harrison, Neil A; Hallett, Mark

    2013-05-01

    Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

  5. No Effects of Bilateral tDCS over Inferior Frontal Gyrus on Response Inhibition and Aggression.

    Directory of Open Access Journals (Sweden)

    Franziska Dambacher

    Full Text Available Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses to the right and approach motivation (relevant for aggressive actions to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS to the inferior frontal cortex. In one group we induced right-hemispheric fronto-cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT and aggression with the Taylor Aggression Paradigm (TAP. We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of t

  6. Proactive modulation of long-interval intracortical inhibition during response inhibition

    Science.gov (United States)

    Cowie, Matthew J.; MacDonald, Hayley J.; Cirillo, John

    2016-01-01

    Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a “default” nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective “brake” is applied. PMID:27281744

  7. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  8. Memory, verbal fluency, and response inhibition in normal aging

    Directory of Open Access Journals (Sweden)

    Gaurav Thapliyal

    2016-01-01

    Full Text Available Background: The concepts of aging-related cognitive changes have appeared to be a major challenge in the society. In this context, the present study was planned to find out the functioning of aging population on different neurocognitive measures. Aims: The aim of the study was to find out the neurocognitive functioning, namely memory, verbal fluency, and response inhibition of normal aging population. Materials and Methods: Following purposive sampling technique, a total of 50 healthy subjects (30 males and 20 females in the age range of 60-70 years were recruited from Jaipur city of Rajasthan. Mini-mental state Examination, PGI memory scale, animal names test, and Stroop test were administered. Results: The findings reveal dysfunction in almost all the domains of memory, namely mental balance, attention and concentration, delayed recall, verbal retention for dissimilar pairs, visual retention and recognition, immediate recall, verbal retention for similar pairs, and visual retention. In domain of verbal fluency, all subjects gave low responses on the animal names test. In domain of response inhibition, all the subjects took less time in color test as compared to color word test on the Stroop task. Conclusions: Findings suggest that there are dysfunction in the area of memory, verbal fluency, and response inhibition in persons aged 60-70 years. However, recent and remote memory were found to be intact.

  9. Response competition and response inhibition during different choice-discrimination tasks: evidence from ERP measured inside MRI scanner.

    Science.gov (United States)

    Gonzalez-Rosa, Javier J; Inuggi, Alberto; Blasi, Valeria; Cursi, Marco; Annovazzi, Pietro; Comi, Giancarlo; Falini, Andrea; Leocani, Letizia

    2013-07-01

    We investigated the neural correlates underlying response inhibition and conflict detection processes using ERPs and source localization analyses simultaneously acquired during fMRI scanning. ERPs were elicited by a simple reaction time task (SRT), a Go/NoGo task, and a Stroop-like task (CST). The cognitive conflict was thus manipulated in order to probe the degree to which information processing is shared across cognitive systems. We proposed to dissociate inhibition and interference conflict effects on brain activity by using identical Stroop-like congruent/incongruent stimuli in all three task contexts and while varying the response required. NoGo-incongruent trials showed a larger N2 and enhanced activations of rostral anterior cingulate cortex (ACC) and pre-supplementary motor area, whereas Go-congruent trials showed a larger P3 and increased parietal activations. Congruent and incongruent conditions of the CST task also elicited similar N2, P3 and late negativity (LN) ERPs, though CST-incongruent trials revealed a larger LN and enhanced prefrontal and ACC activations. Considering the stimulus probability and experimental manipulation of our study, current findings suggest that NoGo N2 and frontal NoGo P3 appear to be more associated to response inhibition rather than a specific conflict monitoring, whereas occipito-parietal P3 of Go and CST conditions may be more linked to a planned response competition between the prepared and required response. LN, however, appears to be related to higher level conflict monitoring associated with response choice-discrimination but not when the presence of cognitive conflict is associated with response inhibition. Copyright © 2013. Published by Elsevier B.V.

  10. Exogenously triggered response inhibition in developmental stuttering.

    Science.gov (United States)

    Eggers, Kurt; De Nil, Luc F; Van den Bergh, Bea R H

    2018-06-01

    The purpose of the present study was to examine relations between children's exogenously triggered response inhibition and stuttering. Participants were 18 children who stutter (CWS; mean age = 9;01 years) and 18 children who not stutter (CWNS; mean age = 9;01 years). Participants were matched on age (±3 months) and gender. Response inhibition was assessed by a stop signal task (Verbruggen, Logan, & Stevens, 2008). Results suggest that CWS, compared to CWNS, perform comparable to CWNS in a task where response control is externally triggered. Our findings seem to indicate that previous questionnaire-based findings (Eggers, De Nil, & Van den Bergh, 2010) of a decreased efficiency of response inhibition cannot be generalized to all types of response inhibition. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Response Inhibition in Adults with Autism Spectrum Disorder Compared to Attention Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Johnston, Kate; Madden, Anya K.; Bramham, Jessica; Russell, Ailsa J.

    2011-01-01

    Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are hypothesised to involve core deficits in executive function. Previous studies have found evidence of a double dissociation between the disorders on specific executive functions (planning and response inhibition). To date most research has been conducted with…

  12. Is transcranial direct current stimulation a potential method for improving response inhibition?☆

    OpenAIRE

    Kwon, Yong Hyun; Kwon, Jung Won

    2013-01-01

    Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the tran...

  13. STIR: Assessing and Training Response Inhibition Abilities

    Science.gov (United States)

    2014-07-30

    Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. Addiction ...requires an abstract application of the core learning principle1,2, and viable examples are often hard to find and/or assess. If exposure to non...inhibition training that expands upon previous successful “near transfer” response inhibition training efforts—such as treating alcohol addictions by

  14. Contrasting neural effects of aging on proactive and reactive response inhibition

    NARCIS (Netherlands)

    Bloemendaal, Mirjam; Zandbelt, Bram; Wegman, Joost; Rest, van de O.; Cools, Roshan; Aarts, Esther

    2016-01-01

    Two distinct forms of response inhibition may underlie observed deficits in response inhibition in aging. We assessed whether age-related neurocognitive impairments in response inhibition reflect deficient reactive inhibition (outright stopping) or also deficient proactive inhibition

  15. Neural Synchrony during Response Production and Inhibition

    Science.gov (United States)

    Müller, Viktor; Anokhin, Andrey P.

    2012-01-01

    Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300–600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations. PMID:22745691

  16. Neural synchrony during response production and inhibition.

    Directory of Open Access Journals (Sweden)

    Viktor Müller

    Full Text Available Inhibition of irrelevant information (conflict monitoring and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.

  17. Transcriptome dynamics of the microRNA inhibition response

    DEFF Research Database (Denmark)

    Wen, Jiayu; Leucci, Elenora; Vendramin, Roberto

    2015-01-01

    We report a high-resolution time series study of transcriptome dynamics following antimiR-mediated inhibition of miR-9 in a Hodgkin lymphoma cell-line-the first such dynamic study of the microRNA inhibition response-revealing both general and specific aspects of the physiological response. We show...... validate the key observations with independent time series qPCR and we experimentally validate key predicted miR-9 targets. Methodologically, we developed sensitive functional data analytic predictive methods to analyse the weak response inherent in microRNA inhibition experiments. The methods...... of this study will be applicable to similar high-resolution time series transcriptome analyses and provides the context for more accurate experimental design and interpretation of future microRNA inhibition studies....

  18. Enhanced prefrontal function with pharmacotherapy on a response inhibition task in adolescent bipolar disorder.

    Science.gov (United States)

    Pavuluri, Mani N; Passarotti, Alessandra M; Harral, Erin M; Sweeney, John A

    2010-11-01

    The aim of the current study is to determine whether pharmacotherapy normalizes cognitive circuitry function supporting voluntary behavioral inhibition in adolescent bipolar disorder. Healthy controls and unmedicated patients with DSM-IV adolescent bipolar disorder in manic, mixed, or hypomanic episodes were matched on demographics and IQ (n = 13 per group; mean age = 14.4 ± 2.4 years). Functional magnetic resonance imaging studies were performed at baseline and after 14 weeks, during which time patients with adolescent bipolar disorder were treated initially with second-generation antipsychotics (SGAs) followed by lamotrigine monotherapy. The primary outcome measure was a Response Inhibition Task, which involved a planned motor response, already "on the way" to execution, that had to be voluntarily inhibited by the subjects in the trials in which a stop signal was presented. There were 6 blocks, each with a predominant rate of either "go" or "stop" trials. The study was conducted from June 2006 through July 2009. All patients showed significant improvement (P adolescent bipolar disorder group than in healthy controls. Increased ventrolateral prefrontal cortex function was related to clinical treatment response. Treatment with SGAs followed by lamotrigine monotherapy enhanced prefrontal and temporal lobe activity during a Response Inhibition Task demonstrating the reversal of disorder-relevant neural circuitry dysfunction in patients with adolescent bipolar disorder. Patient performance was not slowed down with this treatment regimen. clinicaltrials.gov Identifier: NCT00176228. © Copyright 2010 Physicians Postgraduate Press, Inc.

  19. Effective operational oil spill response planning

    International Nuclear Information System (INIS)

    Meyers, R.J.

    1991-01-01

    An operational Contingency Plan is one of the single most important aspects of effective oil spill response operations. It is a spill control game plan. A thorough contingency plan provides a set of guidelines that can be used to help direct all phases of spill response activities. More than simple a compilation of lists and rosters, the contingency plan reflects strategic and philosophical elements of spill response that help to ensure a viable response to any spill incident. Facilities and oil carrying vessels should have well maintained contingency plans with these features. This paper describes the requirement for effective oil spill response pans and the training required to exercise them

  20. Oil spill response plan

    International Nuclear Information System (INIS)

    1999-08-01

    The plan outlined in this document specifies the actions that the Canadian Wildlife Service Atlantic Region is mandated to take in the event of an oil spill, or on discovering oiled migratory birds in terrestrial, fresh water, marine and inter-tidal habitats. In addition to describing the role and responsibilities of the Canadian Wildlife Service, the document also describes response plans of other agencies for dealing with all wildlife species affected by oil spills. Reporting paths, the lead agency concept, shared responsibilities with other Canadian Wildlife Service regional offices, provincial agencies, Heritage Canada, non-government wildlife response agencies, oil spill response organizations, and international organizations are outlined. An overview of the reporting and communications process is also provided

  1. Neural Correlates of Response Inhibition and Conflict Control on Facial Expressions

    Directory of Open Access Journals (Sweden)

    Tongran Liu

    2018-01-01

    Full Text Available Response inhibition and conflict control on affective information can be regarded as two important emotion regulation and cognitive control processes. The emotional Go/Nogo flanker paradigm was adopted and participant’s event-related potentials (ERPs were analyzed to investigate how response inhibition and conflict control interplayed. The behavioral findings revealed that participants showed higher accuracy to identify happy faces in congruent condition relative to that in incongruent condition. The electrophysiological results manifested that response inhibition and conflict control interplayed during the detection/conflict monitoring stage, and Nogo-N2 was more negative in the incongruent trials than the congruent trials. With regard to the inhibitory control/conflict resolution stage, Nogo responses induced greater frontal P3 and parietal P3 responses than Go responses did. The difference waveforms of N2 and parietal P3 showed that response inhibition and conflict control had distinct processes, and the multiple responses requiring both conflict control and response inhibition processes induced stronger monitoring and resolution processes than conflict control. The current study manifested that response inhibition and conflict control on emotional information required separable neural mechanisms during emotion regulation processes.

  2. Is transcranial direct current stimulation a potential method for improving response inhibition?

    Science.gov (United States)

    Kwon, Yong Hyun; Kwon, Jung Won

    2013-04-15

    Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area (pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase). Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

  3. Planned home birth: the professional responsibility response.

    Science.gov (United States)

    Chervenak, Frank A; McCullough, Laurence B; Brent, Robert L; Levene, Malcolm I; Arabin, Birgit

    2013-01-01

    This article addresses the recrudescence of and new support for midwife-supervised planned home birth in the United States and the other developed countries in the context of professional responsibility. Advocates of planned home birth have emphasized patient safety, patient satisfaction, cost effectiveness, and respect for women's rights. We provide a critical evaluation of each of these claims and identify professionally appropriate responses of obstetricians and other concerned physicians to planned home birth. We start with patient safety and show that planned home birth has unnecessary, preventable, irremediable increased risk of harm for pregnant, fetal, and neonatal patients. We document that the persistently high rates of emergency transport undermines patient safety and satisfaction, the raison d'etre of planned home birth, and that a comprehensive analysis undermines claims about the cost-effectiveness of planned home birth. We then argue that obstetricians and other concerned physicians should understand, identify, and correct the root causes of the recrudescence of planned home birth; respond to expressions of interest in planned home birth by women with evidence-based recommendations against it; refuse to participate in planned home birth; but still provide excellent and compassionate emergency obstetric care to women transported from planned home birth. We explain why obstetricians should not participate in or refer to randomized clinical trials of planned home vs planned hospital birth. We call on obstetricians, other concerned physicians, midwives and other obstetric providers, and their professional associations not to support planned home birth when there are safe and compassionate hospital-based alternatives and to advocate for a safe home-birth-like experience in the hospital. Copyright © 2013 Mosby, Inc. All rights reserved.

  4. Prepotent response inhibition predicts treatment outcome in attention deficit/hyperactivity disorder

    NARCIS (Netherlands)

    van der Oord, S.; Geurts, H.M.; Prins, P.J.M.; Emmelkamp, P.M.G.; Oosterlaan, J.

    2012-01-01

    Objective: Inhibition deficits, including deficits in prepotent response inhibition and interference control, are core deficits in ADHD. The predictive value of prepotent response inhibition and interference control was assessed for outcome in a 10-week treatment trial with methylphenidate. Methods:

  5. Prepulse inhibition of auditory change-related cortical responses

    Directory of Open Access Journals (Sweden)

    Inui Koji

    2012-10-01

    Full Text Available Abstract Background Prepulse inhibition (PPI of the startle response is an important tool to investigate the biology of schizophrenia. PPI is usually observed by use of a startle reflex such as blinking following an intense sound. A similar phenomenon has not been reported for cortical responses. Results In 12 healthy subjects, change-related cortical activity in response to an abrupt increase of sound pressure by 5 dB above the background of 65 dB SPL (test stimulus was measured using magnetoencephalography. The test stimulus evoked a clear cortical response peaking at around 130 ms (Change-N1m. In Experiment 1, effects of the intensity of a prepulse (0.5 ~ 5 dB on the test response were examined using a paired stimulation paradigm. In Experiment 2, effects of the interval between the prepulse and test stimulus were examined using interstimulus intervals (ISIs of 50 ~ 350 ms. When the test stimulus was preceded by the prepulse, the Change-N1m was more strongly inhibited by a stronger prepulse (Experiment 1 and a shorter ISI prepulse (Experiment 2. In addition, the amplitude of the test Change-N1m correlated positively with both the amplitude of the prepulse-evoked response and the degree of inhibition, suggesting that subjects who are more sensitive to the auditory change are more strongly inhibited by the prepulse. Conclusions Since Change-N1m is easy to measure and control, it would be a valuable tool to investigate mechanisms of sensory gating or the biology of certain mental diseases such as schizophrenia.

  6. Atomoxetine restores the response inhibition network in Parkinson's disease.

    Science.gov (United States)

    Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-08-01

    Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction

  7. Transport accident emergency response plan

    International Nuclear Information System (INIS)

    Vallette-Fontaine, M.; Frantz, P.

    1998-01-01

    To comply with the IAEA recommendations for the implementation of an Emergency Response Plan as described in Safety Series 87, Transnucleaire, a company deeply involved in the road and rail transports of the fuel cycle, masters means of Emergency Response in the event of a transport accident. This paper aims at analyzing the solutions adopted for the implementation of an Emergency Response Plan and the development of a technical support and adapted means for the recovery of heavy packagings. (authors)

  8. Response inhibition under alcohol: effects of cognitive and motivational conflict.

    Science.gov (United States)

    Fillmore, M T; Vogel-Sprott, M

    2000-03-01

    This experiment tested the effect of cognitive and motivational conflict on response inhibition under alcohol. Fifty-six male social drinkers were randomly assigned to one of eight groups (n = 8). Four pairs of groups received 0.62 g/kg of alcohol, or a placebo, and each pair performed a go/stop choice reaction time task under one of four conflict conditions. One condition (C) produced cognitive conflict by presenting "go" and "stop" signals in the task. Another condition (IR) added motivational conflict by administering an equal monetary reward for inhibiting responses to stop-signals, and for responding to go-signals. The remaining two conditions resolved the motivational conflict by administering the monetary reward only for inhibitions (I), or only for responses (R). Compared with placebo, alcohol reduced inhibitions (i.e., impaired inhibitory control) under cognitive conflict (C; p = .041) and under motivational conflict (IR; p = .012). No significant effect of alcohol on inhibitions was observed in conditions where conflict was resolved (i.e., I and R). The study shows that alcohol can reduce the ability to inhibit a response. However, impaired inhibitory control is not an inevitable outcome of the drug action, because it can be counteracted by the consequences of behavior in the situation.

  9. Improving response inhibition in Parkinson's disease with atomoxetine.

    Science.gov (United States)

    Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2015-04-15

    Dopaminergic drugs remain the mainstay of Parkinson's disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Patients with Parkinson's disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson's disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson's disease. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  10. Inhibition of the immune response to experimental fresh osteoarticular allografts

    International Nuclear Information System (INIS)

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. III; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M.

    1989-01-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed

  11. Sex differences in emotional contexts modulation on response inhibition.

    Science.gov (United States)

    Ramos-Loyo, Julieta; Angulo-Chavira, Armando; Llamas-Alonso, Luis A; González-Garrido, Andrés A

    2016-10-01

    The aim of the present study was to explore sex differences in the effects that emotional contexts exert on the temporal course of response inhibition using event-related potentials (ERP). Participants performed a Go-NoGo response inhibition task under 3 context conditions: with 1) neutral background stimuli, and 2) pleasant, and 3) unpleasant emotional contexts. No sex differences were found in relation to accuracy. Women showed higher N2NoGo amplitudes than men in both emotional contexts; whereas during inhibition men tended to show higher P3NoGo amplitudes than women in the unpleasant context. Both groups experienced a relevant effect of the presence of the unpleasant context during inhibition processing, as shown by the enhancement of the N2NoGo amplitudes in frontal regions compared to results from the neutral and pleasant conditions. In addition, women showed differences between the pleasant and unpleasant contexts, with the latter inducing higher amplitude values. Only in men did inhibition accuracy correlate with higher N2NoGo and lower P3NoGo amplitudes in the emotional context conditions. These findings suggest that when an inhibition task is performed in an emotionally-neutral background context no sex differences are observed in either accuracy or ERP components. However, when the emotional context was introduced -especially the unpleasant one- some gender differences did become evident. The higher N2NoGo amplitude at the presence of the unpleasant context may reflect an effect on attention and conflict monitoring. In addition, results suggest that during earlier processing stages, women invested more resources to process inhibition than men. Furthermore, men who invested more neural resources during earlier stages showed better response inhibition than those who did it during later processing stages, more closely-related to cognitive and motor inhibition processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Directory of Open Access Journals (Sweden)

    Daniel W Bryden

    2012-09-01

    Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

  13. Atomoxetine restores the response inhibition network in Parkinson’s disease

    Science.gov (United States)

    Rae, Charlotte L.; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E.; Jones, P. Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Parkinson’s disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson’s disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson’s disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson’s disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson’s disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced

  14. Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

    Science.gov (United States)

    Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

    2014-10-01

    It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Emergency planning and response - role nad responsibilities of the regulatory body

    International Nuclear Information System (INIS)

    Nizamska, M.

    1999-01-01

    The development of a emergency plan and organisation of adequate emergency preparedness in case of radiological accident in NPP cannot be effective without the appropriate preparatory work. In most countries, also in Republic of Bulgaria, several organisations are identified to have a potential role to play in a radiological emergency. For these reason is very important to have a national organisation, with a mandate to organise, inspect and co-ordinate the possibility of ministries and institution to react in case of radiological emergency, i.e. to quarantine the possibility for implementation of adequate counter measure for protection of the population and environment in case of radiological emergency in NPP. For the purposes of the emergency planning and response the NPP operator, ministries and the institutions developed an Emergency plan - NPP Emergency Plan and National Emergency Plan. The development of the emergency plans will be impossible without the good co-operation of the organisations which have a responsibilities in a radiological emergency. Once emergency plans are adopted, each individual organisation, also the NPP operator, must ensure that in can carry out its role effectively in accordance with the emergency plan and can develop the appropriate organisation for action and implementation of protection counter measures. For testing the emergency plans a regular exercise must be organised. Periodic reviews of the plan and modifications, based on actual events and exercise experience must be performed. The main aim of these report is to present the Bulgarian emergency planning organisation and response by explaining the national emergency panning and response legislation, implementation of IAEA recommendations and exercise experience

  16. The Effectiveness of Reward and Punishment Contingencies on Response Inhibition

    Science.gov (United States)

    Costantini, Arthur F.; Hoving, Kenneth L.

    1973-01-01

    The relative effectiveness of reward and punishment on the development of response inhibition was evaluated developmentally with kindergarteners and second graders. Removal of positive reinforcers was apparently more effective than reward in producing inhibiting at both age levels. Transfer of inhibition training was also evaluated. (DP)

  17. Acrolein in cigarette smoke inhibits T-cell responses.

    Science.gov (United States)

    Lambert, Cherie; McCue, Jesica; Portas, Mary; Ouyang, Yanli; Li, JiMei; Rosano, Thomas G; Lazis, Alexander; Freed, Brian M

    2005-10-01

    Cigarette smoking inhibits T-cell responses in the lungs, but the immunosuppressive compounds have not been fully identified. Cigarette smoke extracts inhibit IL-2, IFN-gamma, and TNF-alpha production in stimulated lymphocytes obtained from peripheral blood, even when the extracts were diluted 100-fold to 1000-fold. The objective of these studies was to identify the immunosuppressive compounds found in cigarette smoke. Gas chromatography/mass spectroscopy and HPLC were used to identify and quantitate volatile compounds found in cigarette smoke extracts. Bioactivity was measured by viability and production of cytokine mRNA and protein levels in treated human lymphocytes. The vapor phase of the cigarette smoke extract inhibited cytokine production, indicating that the immunosuppressive compounds were volatile. Among the volatile compounds identified in cigarette smoke extracts, only the alpha,beta-unsaturated aldehydes, acrolein (inhibitory concentration of 50% [IC50] = 3 micromol/L) and crotonaldehyde (IC50 = 6 micromol/L), exhibited significant inhibition of cytokine production. Although the levels of aldehydes varied 10-fold between high-tar (Camel) and ultralow-tar (Carlton) extracts, even ultralow-tar cigarettes produced sufficient levels of acrolein (34 micromol/L) to suppress cytokine production by >95%. We determined that the cigarette smoke extract inhibited transcription of cytokine genes. The inhibitory effects of acrolein could be blocked with the thiol compound N-acetylcysteine. The vapor phase from cigarette smoke extracts potently suppresses cytokine production. The compound responsible for this inhibition appears to be acrolein.

  18. Response Inhibition and Internet Gaming Disorder: A Meta-analysis.

    Science.gov (United States)

    Argyriou, Evangelia; Davison, Christopher B; Lee, Tayla T C

    2017-08-01

    Previous research has demonstrated that Internet Gaming Disorder (IGD) has multiple negative effects in psychological functioning and health. This makes the identification of its underpinnings, such as response inhibition, essential for the development of relevant interventions that target these core features of the disorder resulting in more effective treatment. Several empirical studies have evaluated the relationship between response inhibition deficits and IGD using neurocognitive tasks, but provided mixed results. In this study, we conducted a meta-analysis of studies using three neurocognitive tasks, the Go/No Go, the Stroop, and the Stop-Signal tasks, to integrate existing research and estimate the magnitude of this relationship. We found a medium overall effect size (d=0.56, 95% CI [0.32, 0.80]) indicating that compared with healthy individuals, individuals with IGD are more likely to exhibit impaired response inhibition. This finding is in alignment with literature on inhibition and addictive and impulsive behaviors, as well as with neuroimaging research. Theoretical implications regarding the conceptualization of IGD as a clinical disorder, shared commonalities with externalizing psychopathology, and clinical implications for treatment are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Reinforcement and stimulant medication ameliorate deficient response inhibition in children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Rosch, Keri S.; Fosco, Whitney D.; Pelham, William E.; Waxmonsky, James G.; Bubnik, Michelle G.; Hawk, Larry W.

    2015-01-01

    This study examined the degree to which reinforcement, stimulant medication, and their combination impact response inhibition in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Across three studies, participants with ADHD (n=111, 25 girls) and typically-developing (TD) controls (n=33, 6 girls) completed a standard version of the stop signal task (SST) and/or a reinforcement-manipulation SST with performance-contingent points. In two of these studies, these tasks were performed under placebo or 0.3 and 0.6 mg/kg methylphenidate (MPH) conditions. Cross-study comparisons were conducted to test hypotheses regarding the separate and combined effects of reinforcement and methylphenidate on response inhibition among children with ADHD relative to TD controls. Baseline response inhibition was worse among children with ADHD compared to controls. MPH produced dose-related improvements in response inhibition in children with ADHD; compared to non-medicated TD controls, 0.3 mg/kg MPH normalized deficient response inhibition, and 0.6 mg/kg MPH resulted in better inhibition in children with ADHD. Reinforcement improved response inhibition to a greater extent for children with ADHD than for TD children, normalizing response inhibition. The combination of MPH and reinforcement improved response inhibition among children with ADHD compared to reinforcement alone and MPH alone, also resulting in normalization of response inhibition despite repeated task exposure. Deficient response inhibition commonly observed in children with ADHD is significantly improved with MPH and/or reinforcement, normalizing inhibition relative to TD children tested under standard conditions. PMID:25985978

  20. Resisting distraction and response inhibition trigger similar enhancements of future performance.

    Science.gov (United States)

    Bissett, Patrick G; Grant, Lauren D; Weissman, Daniel H

    2017-10-01

    Resisting distraction and response inhibition are crucial aspects of cognitive control. Interestingly, each of these abilities transiently improves just after it is utilized. Competing views differ, however, as to whether utilizing either of these abilities (e.g., resisting distraction) enhances future performance involving the other ability (e.g., response inhibition). To distinguish between these views, we combined a Stroop-like task that requires resisting distraction with a restraint variant of the stop-signal task that requires response inhibition. We observed similar sequential-trial effects (i.e., performance enhancements) following trials in which participants (a) resisted distraction (i.e., incongruent go trials) and (b) inhibited a response (i.e., congruent stop trials). First, the congruency effect in go trials, which indexes overall distractibility, was smaller after both incongruent go trials and congruent stop trials than it was after congruent go trials. Second, stop failures were less frequent after both incongruent go trials and congruent stop trials than after congruent go trials. A control experiment ruled out the possibility that perceptual conflict or surprise engendered by occasional stop signals triggers sequential-trial effects independent of stopping. Thus, our findings support a novel, integrated view in which resisting distraction and response inhibition trigger similar sequential enhancements of future performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Maturation of cognitive control: delineating response inhibition and interference suppression.

    Directory of Open Access Journals (Sweden)

    Christopher R Brydges

    Full Text Available Cognitive control is integral to the ability to attend to a relevant task whilst suppressing distracting information or inhibiting prepotent responses. The current study examined the development of these two subprocesses by examining electrophysiological indices elicited during each process. Thirteen 18 year-old adults and thirteen children aged 8-11 years (mean=9.77 years completed a hybrid Go/Nogo flanker task while continuous EEG data were recorded. The N2 topography for both response inhibition and interference suppression changed with increasing age. The neural activation associated with response inhibition became increasingly frontally distributed with age, and showed decreases of both amplitude and peak latency from childhood to adulthood, possibly due to reduced cognitive demands and myelination respectively occurring during this period. Interestingly, a significant N2 effect was apparent in adults, but not observed in children during trials requiring interference suppression. This could be due to more diffuse activation in children, which would require smaller levels of activation over a larger region of the brain than is reported in adults. Overall, these results provide evidence of distinct maturational processes occurring throughout late childhood and adolescence, highlighting the separability of response inhibition and interference suppression.

  2. The neural markers of an imminent failure of response inhibition.

    Science.gov (United States)

    Bengson, Jesse J; Mangun, George R; Mazaheri, Ali

    2012-01-16

    In his novel Ulysses, James Joyce wrote that mistakes are the "…portals of discovery". The present study investigated the pre-stimulus oscillatory EEG signatures of selective attention and motor preparation that predicted failures of overt response inhibition. We employed a trial-by-trial spatial cueing task using a go/no-go response paradigm with bilateral target stimuli. Subjects were required to covertly attend to the spatial location cued on each trial and respond to most of the number targets (go trials) at that location while withholding responses for one designated number (no-go trials). We analyzed the post-cue/pre-target spectral patterns comparing no-go trials in which a response occurred in error (False Alarms, FA) with trials in which participants correctly withheld a response (Correct Rejections, CR). We found that cue-induced occipital alpha (8-12 Hz) lateralization and inter-frequency anti-correlations between the motor beta (18-24 Hz) and pre-frontal theta (3-5 Hz) bands each independently predicted subsequent failures of response inhibition. Based on these findings, we infer that independent perceptual and motor mechanisms operate in parallel to contribute to failures of response inhibition. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Improving Response Inhibition in Parkinson’s Disease with Atomoxetine

    Science.gov (United States)

    Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R.; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L.; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.; Rowe, James B.

    2015-01-01

    Background Dopaminergic drugs remain the mainstay of Parkinson’s disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. Methods This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Results Patients with Parkinson’s disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. Conclusions This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson’s disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson’s disease. PMID:24655598

  4. Resisting temptation: decreasing alcohol-related affect and drinking behavior by training response inhibition

    NARCIS (Netherlands)

    Houben, K.; Nederkoorn, C.; Wiers, R.W.; Jansen, A.

    2011-01-01

    According to dual-process models, excessive alcohol use emerges when response inhibition ability is insufficient to inhibit automatic impulses to drink alcohol. This study examined whether strengthening response inhibition for alcohol-related cues decreases alcohol intake. Fifty-two heavy drinking

  5. Impaired right inferior frontal gyrus response to contextual cues in male veterans with PTSD during response inhibition.

    Science.gov (United States)

    van Rooij, Sanne J H; Rademaker, Arthur R; Kennis, Mitzy; Vink, Matthijs; Kahn, René S; Geuze, Elbert

    2014-09-01

    Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated. Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues). We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group. Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups. Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit.

  6. Genetic influences on phase synchrony of brain oscillations supporting response inhibition.

    Science.gov (United States)

    Müller, Viktor; Anokhin, Andrey P; Lindenberger, Ulman

    2017-05-01

    Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

    OpenAIRE

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J.; Stunden, H. James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R.; Cain, Jason E.; Bardin, Philip G.; Williams, Bryan R. G.; Gantier, Michael P.

    2017-01-01

    ABSTRACT Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through c...

  8. Acute LSD effects on response inhibition neural networks.

    Science.gov (United States)

    Schmidt, A; Müller, F; Lenz, C; Dolder, P C; Schmid, Y; Zanchi, D; Lang, U E; Liechti, M E; Borgwardt, S

    2017-10-02

    Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations. In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire. Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery. Our findings show that 5-HT2AR activation by LSD leads to a hippocampal-prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.

  9. A model national emergency response plan for radiological accidents

    International Nuclear Information System (INIS)

    1993-09-01

    The IAEA has supported several projects for the development of a national response plan for radiological emergencies. As a results, the IAEA has developed a model National Emergency Response Plan for Radiological Accidents (RAD PLAN), particularly for countries that have no nuclear power plants. This plan can be adapted for use by countries interested in developing their own national radiological emergency response plan, and the IAEA will supply the latest version of the RAD PLAN on computer diskette upon request. 2 tabs

  10. Exercising the federal radiological emergency response plan

    International Nuclear Information System (INIS)

    Gant, K.S.; Adler, M.V.; Wolff, W.F.

    1986-01-01

    Multiagency exercises were an important part of the development of the Federal Radiological Emergency Response Plan. This paper concentrates on two of these exercises, the Federal Field Exercise in March 1984 and the Relocation Tabletop Exercise in December 1985. The Federal Field Exercise demonstrated the viability and usefulness of the draft plan; lessons learned from the exercise were incorporated into the published plan. The Relocation Tabletop Exercise examined the federal response in the postemergency phase. This exercise highlighted the change over time in the roles of some agencies and suggested response procedures that should be developed or revised. 8 refs

  11. Emotion potentiates response activation and inhibition in masked priming.

    Science.gov (United States)

    Bocanegra, Bruno R; Zeelenberg, René

    2012-01-01

    Previous studies have shown that emotion can have 2-fold effects on perception. At the object-level, emotional stimuli benefit from a stimulus-specific boost in visual attention at the relative expense of competing stimuli. At the visual feature-level, recent findings indicate that emotion may inhibit the processing of small visual details and facilitate the processing of coarse visual features. In the present study, we investigated whether emotion can boost the activation and inhibition of automatic motor responses that are generated prior to overt perception. To investigate this, we tested whether an emotional cue affects covert motor responses in a masked priming task. We used a masked priming paradigm in which participants responded to target arrows that were preceded by invisible congruent or incongruent prime arrows. In the standard paradigm, participants react faster, and commit fewer errors responding to the directionality of target arrows, when they are preceded by congruent vs. incongruent masked prime arrows (positive congruency effect, PCE). However, as prime-target SOAs increase, this effect reverses (negative congruency effect, NCE). These findings have been explained as evidence for an initial activation and a subsequent inhibition of a partial response elicited by the masked prime arrow. Our results show that the presentation of fearful face cues, compared to neutral face cues, increased the size of both the PCE and NCE, despite the fact that the primes were invisible. This is the first demonstration that emotion prepares an individual's visuomotor system for automatic activation and inhibition of motor responses in the absence of visual awareness.

  12. High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

    Science.gov (United States)

    Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

    2016-01-01

    Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

  13. Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation.

    Science.gov (United States)

    Strempel, Sebastian; Schroeder, Christoph; Hemmersbach, Ruth; Boese, Andrea; Tank, Jens; Diedrich, André; Heer, Martina; Luft, Friedrich C; Jordan, Jens

    2008-03-01

    Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 +/- 1 yr, body mass index 24 +/- 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.

  14. Emergency response planning in Saskatchewan

    International Nuclear Information System (INIS)

    Irwin, R.W.

    1998-01-01

    Release reporting and spill clean-up requirements by Saskatchewan Energy and Mines were reviewed. Wascana's experience in response planning was discussed. It was suggested that the key to prevention was up-front due diligence, including facility and oil well analysis. Details of Wascana's emergency plan, and details of Saskatchewan Energy and Mines release reporting procedures were also provided

  15. The C protein of measles virus inhibits the type I interferon response

    International Nuclear Information System (INIS)

    Shaffer, Jessica A.; Bellini, William J.; Rota, Paul A.

    2003-01-01

    Type I interferons (IFNα/β) are an important part of innate immunity to viral infections because they induce an antiviral response and limit viral replication until the adaptive response clears the infection. Since the nonstructural proteins of several paramyxoviruses inhibit the IFNα/β response, we chose to explore the role of the C protein of measles virus (MV) in such inhibition. Previous studies have suggested that the MV C protein may serve as a virulence factor, but its role in the pathogenesis of MV remains undefined. In the present study, a recombinant MV strain that does not express the C protein (MV C-) and its parental strain (Ed Tag) were used. Growth of MV C- was restricted in human peripheral blood mononuclear cells and HeLa cells, but in the presence of neutralizing antibodies to IFNα/β, MV C- produced titers that were equivalent to those of Ed Tag. In addition, expression of the MV C protein from plasmid DNA inhibited the production of an IFNα/β responsive reporter gene and, to a lesser extent, inhibited an IFNγ responsive reporter gene. The ability of the MV C protein to suppress the IFNα/β response was confirmed using a biologic assay. After IFNβ stimulation, HeLa cells infected with Ed Tag produced five-fold less IFNα/β than cells infected with MV C-. While the mechanism of inhibition remains unclear, these data suggest that the MV C protein plays an important role in the pathogenesis of MV by inhibiting IFNα/β signaling

  16. Response inhibition and interference control in obsessive-compulsive spectrum disorders

    Directory of Open Access Journals (Sweden)

    Laura S van Velzen

    2014-06-01

    Full Text Available Over the past twenty years, motor response inhibition and interference control have received considerable scientific effort and attention, due to their important role in behavior and the development of neuropsychiatric disorders. Results of neuroimaging studies indicate that motor response inhibition and interference control are dependent on cortical-striatal-thalamic-cortical (CSTC circuits. Structural and functional abnormalities within the CSTC circuits have been reported for many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD and related disorders, such as attention deficit hyperactivity disorder (ADHD, Tourette’s syndrome (TS and trichotillomania. These disorders also share impairments in motor response inhibition and interference control, which may underlie some of their behavioral and cognitive symptoms. Results of task-related neuroimaging studies on inhibitory functions in these disorders show that impaired task performance is related to altered recruitment of the CSTC circuits. Previous research has shown that inhibitory performance is dependent upon dopamine, noradrenaline and serotonin signaling, neurotransmitters that have been implicated in the pathophysiology of these disorders. In this review we discuss the common and disorder-specific pathophysiological mechanisms of inhibition-related dysfunction in OCD and related disorders.

  17. Improving response inhibition systems in frontotemporal dementia with citalopram.

    Science.gov (United States)

    Hughes, Laura E; Rittman, Timothy; Regenthal, Ralf; Robbins, Trevor W; Rowe, James B

    2015-07-01

    Disinhibition is a cardinal feature of the behavioural variant of frontotemporal dementia, presenting as impulsive and impetuous behaviours that are often difficult to manage. The options for symptomatic treatments are limited, but a potential target for therapy is the restoration of serotonergic function, which is both deficient in behavioural variant frontotemporal dementia and closely associated with inhibitory control. Based on preclinical studies and psychopharmacological interventions in other disorders, we predicted that inhibition would be associated with the right inferior frontal gyrus and dependent on serotonin. Using magnetoencephalography and electroencephalography of a Go-NoGo paradigm, we investigated the neural basis of behavioural disinhibition in behavioural variant frontotemporal dementia and the effect of selective serotonin reuptake inhibition on the neural systems for response inhibition. In a randomized double-blinded placebo-controlled crossover design study, 12 patients received either a single 30 mg dose of citalopram or placebo. Twenty age-matched healthy controls underwent the same magnetoencephalography/electroencephalography protocol on one session without citalopram, providing normative data for this task. In the control group, successful NoGo trials evoked two established indices of successful response inhibition: the NoGo-N2 and NoGo-P3. Both of these components were significantly attenuated by behavioural variant frontotemporal dementia. Cortical sources associated with successful inhibition in control subjects were identified in the right inferior frontal gyrus and anterior temporal lobe, which have been strongly associated with behavioural inhibition in imaging and lesion studies. These sources were impaired by behavioural variant frontotemporal dementia. Critically, citalopram enhanced the NoGo-P3 signal in patients, relative to placebo treatment, and increased the evoked response in the right inferior frontal gyrus. Voxel

  18. Response inhibition is associated with white matter microstructure in children

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Baaré, William; Vestergaard, Martin

    2010-01-01

    Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving...... to the prediction of performance variability. Observed associations may be related to variation in phase of maturation, to activity-dependent alterations in the network subserving response inhibition, or to stable individual differences in underlying neural system connectivity. (C) 2009 Elsevier Ltd. All rights...

  19. ISS Payload Operations: The Need for and Benefit of Responsive Planning

    Science.gov (United States)

    Nahay, Ed; Boster, Mandee

    2000-01-01

    International Space Station (ISS) payload operations are controlled through implementation of a payload operations plan. This plan, which represents the defined approach to payload operations in general, can vary in terms of level of definition. The detailed plan provides the specific sequence and timing of each component of a payload's operations. Such an approach to planning was implemented in the Spacelab program. The responsive plan provides a flexible approach to payload operations through generalization. A responsive approach to planning was implemented in the NASA/Mir Phase 1 program, and was identified as a need during the Skylab program. The current approach to ISS payload operations planning and control tends toward detailed planning, rather than responsive planning. The use of detailed plans provides for the efficient use of limited resources onboard the ISS. It restricts flexibility in payload operations, which is inconsistent with the dynamic nature of the ISS science program, and it restricts crew desires for flexibility and autonomy. Also, detailed planning is manpower intensive. The development and implementation of a responsive plan provides for a more dynamic, more accommodating, and less manpower intensive approach to planning. The science program becomes more dynamic and responsive as the plan provides flexibility to accommodate real-time science accomplishments. Communications limitations and the crew desire for flexibility and autonomy in plan implementation are readily accommodated with responsive planning. Manpower efficiencies are accomplished through a reduction in requirements collection and coordination, plan development, and maintenance. Through examples and assessments, this paper identifies the need to transition from detailed to responsive plans for ISS payload operations. Examples depict specific characteristics of the plans. Assessments identify the following: the means by which responsive plans accommodate the dynamic nature of

  20. Evaluation criteria for emergency response plans in radiological transportation

    International Nuclear Information System (INIS)

    Lindell, M.K.; Perry, R.W.

    1980-01-01

    This paper identifies a set of general criteria which can be used as guides for evaluating emergency response plans prepared in connection with the transportation of radiological materials. The development of criteria takes the form of examining the meaning and role of emergency plans in general, reviewing the process as it is used in connection with natural disasters and other nonnuclear disasters, and explicitly considering unique aspects of the radiological transportation setting. Eight areas of critical importance for such response plans are isolated: notification procedures; accident assessment; public information; protection of the public at risk; other protective responses; radiological exposure control; responsibility for planning and operations; and emergency response training and exercises. (Auth.)

  1. Environmental aspects of contingency planning and spill response

    International Nuclear Information System (INIS)

    Hillman, S.O.

    1993-01-01

    Alyeska Pipeline Service Company has implemented an incident command system (ICS) for crisis management within the company for response to spills at all company facilities including the Valdez Marine Terminal. The system is also used by Alyeska acting as the initial response contractor for TAPS laden tankers within Prince William Sound. During the past three years, Alyeska has undertaken a complete review of the spill prevention and response plans for these areas. This poster session focuses on the environmental aspects of the response planning efforts. Information is available on contingency planning updates in the areas of dispersant use, burning as a response tool, bioremediation of marine oil spills, waste management, permitting, coastal resource and sensitive habitat data base, and wildlife protection and management. All of these subjects are addressed in the resource documents (RD) supplementing the contingency plans. The RD revisions have been a coordinated effort, involving operators, agencies, and the public through the citizen advisory group

  2. Intraglomerular inhibition maintains mitral cell response contrast across input frequencies.

    Science.gov (United States)

    Shao, Zuoyi; Puche, Adam C; Shipley, Michael T

    2013-11-01

    Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can "sharpen" MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain "contrast" in MC encoding during sniff-sampled inputs.

  3. dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

    Science.gov (United States)

    Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

    2017-08-04

    German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

  4. Oil spill response planning on the Columbia river estuary

    International Nuclear Information System (INIS)

    Christopherson, S.K.; Slyman, P.M.

    1993-01-01

    The Columbia River Estuary lies along the Washington-Oregon state boundary on the west coast of the United States. The entire area is environmentally very sensitive with numerous large, shallow bays, exposed mud flats, wetland areas, and central channels having maximum currents of three to four knots. These features make the area very difficult to protect from an oil spill. Spill response is further complicated because of the many different state, federal, and local jurisdictions with mandated responsibilities in oil spill response and environmental protection. Under the leadership of the US Coast Guard Marine Safety Office in Portland, Oregon, a steering group was established to guide the development of a response plan for the Columbia River Estuary. A concerted effort was made to include representatives from response organizations, natural resource agencies, and resource users from federal, state, and local governments, and commercial sectors in the planning process. The first draft of an operational response plan was completed the summer of 1992 through a combination of technical workshops, field trips, and small working groups meeting with local communities. The Columbia River Estuary Response Plan prioritizes areas to protect; identifies specific response strategies for protecting these areas; and outlines the Iogistics needed to implement these strategies, including equipment needs, the location of staging areas, and the identification of pre-designed command posts. The local spill response cooperative and oil transportation industry are using the plan to coordinate the purchase of response equipment and the staging of this equipment at numerous locations along the river. The key to success is ensuring that all the groups responding to an event participate in the planning process together. This process has worked well and will serve as a model for response planning for other areas along the Columbia River and coastal areas of Washington and Oregon

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Functional neural networks underlying response inhibition in adolescents and adults.

    Science.gov (United States)

    Stevens, Michael C; Kiehl, Kent A; Pearlson, Godfrey D; Calhoun, Vince D

    2007-07-19

    This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by fronto-striatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development.

  7. Responsibility modelling for civil emergency planning

    OpenAIRE

    Sommerville, Ian; Storer, Timothy; Lock, Russell

    2009-01-01

    This paper presents a new approach to analysing and understanding civil emergency planning based on the notion of responsibility modelling combined with HAZOPS-style analysis of information requirements. Our goal is to represent complex contingency plans so that they can be more readily understood, so that inconsistencies can be highlighted and vulnerabilities discovered. In this paper, we outline the framework for contingency planning in the United Kingdom and introduce the notion of respons...

  8. Agency procedures for the NRC incident response plan. Final report

    International Nuclear Information System (INIS)

    1983-02-01

    The NRC Incident Response Plan, NUREG-0728/MC 0502 describes the functions of the NRC during an incident and the kinds of actions that comprise an NRC response. The NRC response plan will be activated in accordance with threshold criteria described in the plan for incidents occurring at nuclear reactors and fuel facilities involving materials licensees; during transportation of licensed material, and for threats against facilities or licensed material. In contrast to the general overview provided by the Plan, the purpose of these agency procedures is to delineate the manner in which each planned response function is performed; the criteria for making those response decisions which can be preplanned; and the information and other resources needed during a response. An inexperienced but qualified person should be able to perform functions assigned by the Plan and make necessary decisions, given the specified information, by becoming familiar with these procedures. This rule of thumb has been used to determine the amount of detail in which the agency procedures are described. These procedures form a foundation for the training of response personnel both in their normal working environment and during planned emergency exercises. These procedures also form a ready reference or reminder checklist for technical team members and managers during a response

  9. The importance of socially responsible strategic planning

    Science.gov (United States)

    Štrukelj, Tjaša

    2017-10-01

    This paper researches the importance of social responsible strategic planning regardless of the sector and shows research results on the case example of the selected tourism sector, which has economic and employment potential and social and environmental implications. Tourism sector is closely interdependent with transport sector and influences it. Therefore, the more we develop the tourism sector, the more the transport sector is developing as well. Based on Mulej’s Dialectical Systems Theory (DST) we found out that enterprises should integrate sustainability and social responsibility into their strategic planning if they want the Earth to survive. This urged the European Union, ISO International Standards Organization, many other organisations and many researchers. To make strategic planning socially responsible, enterprise’s governors should request social responsibility in business policy, which represents their governance guidelines and is implemented through the strategies set up by top managers and realised in the basic realisation process - their business operations.

  10. Emergency response planning in hospitals, United States: 2003-2004.

    Science.gov (United States)

    Niska, Richard W; Burt, Catharine W

    2007-08-20

    This study presents baseline data to determine which hospital characteristics are associated with preparedness for terrorism and natural disaster in the areas of emergency response planning and availability of equipment and specialized care units. Information from the Bioterrorism and Mass Casualty Preparedness Supplements to the 2003 and 2004 National Hospital Ambulatory Medical Care Surveys was used to provide national estimates of variations in hospital emergency response plans and resources by residency and medical school affiliation, hospital size, ownership, metropolitan statistical area status, and Joint Commission accreditation. Of 874 sampled hospitals with emergency or outpatient departments, 739 responded for an 84.6 percent response rate. Estimates are presented with 95 percent confidence intervals. About 92 percent of hospitals had revised their emergency response plans since September 11, 2001, but only about 63 percent had addressed natural disasters and biological, chemical, radiological, and explosive terrorism in those plans. Only about 9 percent of hospitals had provided for all 10 of the response plan components studied. Hospitals had a mean of about 14 personal protective suits, 21 critical care beds, 12 mechanical ventilators, 7 negative pressure isolation rooms, and 2 decontamination showers each. Hospital bed capacity was the factor most consistently associated with emergency response planning and availability of resources.

  11. Spatial frequency information modulates response inhibition and decision-making processes.

    Directory of Open Access Journals (Sweden)

    Sara Jahfari

    Full Text Available We interact with the world through the assessment of available, but sometimes imperfect, sensory information. However, little is known about how variance in the quality of sensory information affects the regulation of controlled actions. In a series of three experiments, comprising a total of seven behavioral studies, we examined how different types of spatial frequency information affect underlying processes of response inhibition and selection. Participants underwent a stop-signal task, a two choice speed/accuracy balance experiment, and a variant of both these tasks where prior information was given about the nature of stimuli. In all experiments, stimuli were either intact, or contained only high-, or low- spatial frequencies. Overall, drift diffusion model analysis showed a decreased rate of information processing when spatial frequencies were removed, whereas the criterion for information accumulation was lowered. When spatial frequency information was intact, the cost of response inhibition increased (longer SSRT, while a correct response was produced faster (shorter reaction times and with more certainty (decreased errors. When we manipulated the motivation to respond with a deadline (i.e., be fast or accurate, removal of spatial frequency information slowed response times only when instructions emphasized accuracy. However, the slowing of response times did not improve error rates, when compared to fast instruction trials. These behavioral studies suggest that the removal of spatial frequency information differentially affects the speed of response initiation, inhibition, and the efficiency to balance fast or accurate responses. More generally, the present results indicate a task-independent influence of basic sensory information on strategic adjustments in action control.

  12. Responsive consumerism: empowerment in markets for health plans.

    Science.gov (United States)

    Elbel, Brian; Schlesinger, Mark

    2009-09-01

    American health policy is increasingly relying on consumerism to improve its performance. This article examines a neglected aspect of medical consumerism: the extent to which consumers respond to problems with their health plans. Using a telephone survey of five thousand consumers conducted in 2002, this article assesses how frequently consumers voice formal grievances or exit from their health plan in response to problems of differing severity. This article also examines the potential impact of this responsiveness on both individuals and the market. In addition, using cross-group comparisons of means and regressions, it looks at how the responses of "empowered" consumers compared with those who are "less empowered." The vast majority of consumers do not formally voice their complaints or exit health plans, even in response to problems with significant consequences. "Empowered" consumers are only minimally more likely to formally voice and no more likely to leave their plan. Moreover, given the greater prevalence of trivial problems, consumers are much more likely to complain or leave their plans because of problems that are not severe. Greater empowerment does not alleviate this. While much of the attention on consumerism has focused on prospective choice, understanding how consumers respond to problems is equally, if not more, important. Relying on consumers' responses as a means to protect individual consumers or influence the market for health plans is unlikely to be successful in its current form.

  13. Frontal White Matter Damage Impairs Response Inhibition in Children Following Traumatic Brain Injury

    Science.gov (United States)

    Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

    2014-01-01

    Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition. PMID:24618405

  14. Effects of High-Definition and Conventional tDCS on Response Inhibition.

    Science.gov (United States)

    Hogeveen, J; Grafman, J; Aboseria, M; David, A; Bikson, M; Hauner, K K

    2016-01-01

    Response inhibition is a critical executive function, enabling the adaptive control of behavior in a changing environment. The inferior frontal cortex (IFC) is considered to be critical for response inhibition, leading researchers to develop transcranial direct current stimulation (tDCS) montages attempting to target the IFC and improve inhibitory performance. However, conventional tDCS montages produce diffuse current through the brain, making it difficult to establish causality between stimulation of any one given brain region and resulting behavioral changes. Recently, high-definition tDCS (HD-tDCS) methods have been developed to target brain regions with increased focality relative to conventional tDCS. Remarkably few studies have utilized HD-tDCS to improve cognitive task performance, however, and no study has directly compared the behavioral effects of HD-tDCS to conventional tDCS. In the present study, participants received either HD-tDCS or conventional tDCS to the IFC during performance of a response inhibition task (stop-signal task, SST) or a control task (choice reaction time task, CRT). A third group of participants completed the same behavioral protocols, but received tDCS to a control site (mid-occipital cortex). Post-stimulation improvement in SST performance was analyzed as a function of tDCS group and the task performed during stimulation using both conventional and Bayesian parameter estimation analyses. Bayesian estimation of the effects of HD- and conventional tDCS to IFC relative to control site stimulation demonstrated enhanced response inhibition for both conditions. No improvements were found after control task (CRT) training in any tDCS condition. Results support the use of both HD- and conventional tDCS to the IFC for improving response inhibition, providing empirical evidence that HD-tDCS can be used to facilitate performance on an executive function task. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise.

    Science.gov (United States)

    Jankord, Ryan; McAllister, Richard M; Ganjam, Venkataseshu K; Laughlin, M Harold

    2009-03-01

    Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NO(x) levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress.

  16. Response inhibition during cue reactivity in problem gamblers: an fMRI study.

    Directory of Open Access Journals (Sweden)

    Ruth J van Holst

    Full Text Available Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition in problem gamblers (PRGs, we designed an affective Go/Nogo to examine the interaction between response inhibition and salience attribution in 16 PRGs and 15 healthy controls (HCs.Four affective blocks were presented with Go trials containing neutral, gamble, positive or negative affective pictures. The No-Go trials in these blocks contained neutral pictures. Outcomes of interest included percentage of impulsive errors and mean reaction times in the different blocks. Brain activity related to No-Go trials was assessed to measure response inhibition in the various affective conditions and brain activity related to Go trials was assessed to measure salience attribution.PRGs made fewer errors during gamble and positive trials than HCs, but were slower during all trials types. Compared to HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and ventral striatum to a greater extent while viewing gamble pictures. The dorsal lateral and inferior frontal cortex were more activated in PRGs than in HCs while viewing positive and negative pictures. During neutral inhibition, PRGs were slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal and anterior cingulate cortex activity. In contrast, during gamble and positive pictures PRGs performed better than HCs, and showed lower activation of the dorsolateral and anterior cingulate cortex.This study shows that gambling-related stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory brain activity to achieve similar performance during neutral response inhibition. A gambling-related or positive context appears to facilitate response inhibition as

  17. Acute serotonin depletion releases motivated inhibition of response vigour.

    Science.gov (United States)

    den Ouden, Hanneke E M; Swart, Jennifer C; Schmidt, Kristin; Fekkes, Durk; Geurts, Dirk E M; Cools, Roshan

    2015-04-01

    The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas, however, has been mixed. In the current study, we aimed to investigate the role of serotonin (5HT) in behavioural vigour as a function of incentive motivation. We employed dietary acute tryptophan depletion (ATD) to lower the 5HT precursor tryptophan during the performance of a speeded visual discrimination task. Feedback valence and feedback probability were manipulated independently and cued prior to target onset. On feedback trials, fast correct responses led to either reward or avoidance of punishment, while slow or incorrect responses led to reward omission or punishment. We show that behavioural responding is inhibited under high incentive motivation (i.e. high-feedback probability) at baseline 5HT levels and that lowering these leads to behavioural disinhibition, while leaving accuracy unaffected. Surprisingly, there were no differential effects of motivational valence, with 5HT depletion releasing behavioural inhibition under both appetitive and aversive motivation. Our findings extend current theories on the role of 5HT in behavioural inhibition by showing that reductions in serotonin lead to increased behavioural vigour only if there is a motivational drive to inhibit behaviour at baseline.

  18. Training and Transfer Effects of Response Inhibition Training in Children and Adults

    Science.gov (United States)

    Zhao, Xin; Chen, Ling; Maes, Joseph H. R.

    2018-01-01

    Response inhibition is crucial for mental and physical health but studies assessing the trainability of this type of inhibition are rare. Thirty-nine children aged 10-12 years and 46 adults aged 18-24 years were assigned to an adaptive go/no-go inhibition training condition or an active control condition. Transfer of training effects to…

  19. Emergency response planning in Pennsylvania

    International Nuclear Information System (INIS)

    Reilly, M.A.

    1988-01-01

    In the decade since the accident at Three Mile Island, emergency planning for response to these events has undergone a significant change in Pennsylvania, as elsewhere. Changes respond to federal guidance and to state agency initiatives. The most singular change is the practice of implementing a protective action throughout the entire emergency planning zone (EPZ). Due to Pennsylvania agency experiences during the accident, the decision was made soon after to develop a staff of nuclear engineers, each giving special day-to-day attention to a specific nuclear power station in the state. Changes in communications capabilities are significant, these being dedicated phone lines between the Commonwealth and each power station, and the reorientation of the Department of Environmental Resources radio network to accommodate direction of field monitoring teams from Harrisburg. Changes that are being or will be implemented in the near future include assessing the emergency response data system for electronic delivery of plant parameter data form facilities during accidents, increased participation in exercises, emergency medical planning, and training, the inclusion of all 67 counties in Pennsylvania in an ingestion EPZ, and the gradual severance of dependence on land-line emergency communication systems

  20. ANS-8.23: Criticality accident emergency planning and response

    International Nuclear Information System (INIS)

    Pruvost, N.L.

    1991-01-01

    A study group has been formed under the auspices of ANS-8 to examine the need for a standard on nuclear criticality accident emergency planning and response. This standard would be ANS-8.23. ANSI/ANS-8.19-1984, Administrative Practices for Nuclear Criticality Safety, provides some guidance on the subject in Section 10 titled -- Planned Response to Nuclear Criticality Accidents. However, the study group has formed a consensus that Section 10 is inadequate in that technical guidance in addition to administrative guidance is needed. The group believes that a new standard which specifically addresses emergency planning and response to a perceived criticality accident is needed. Plans for underway to request the study group be designated a writing group to create a draft of such a new standard. The proposed standard will divide responsibility between management and technical staff. Generally, management will be charged with providing the necessary elements of emergency planning such as a criticality detection and alarm system, training, safe evacuation routes and assembly areas, a system for timely accountability of personnel, and an effective emergency response organization. The technical staff, on the other hand, will be made responsible for establishing specific items such as safe and clearly posted evacuation evacuation routes and dose criteria for personnel assembly areas. The key to the question of responsibilities is that management must provide the resources for the technical staff to establish the elements of an emergency response effort

  1. The effect of methylphenidate on three forms of response inhibition in boys with AD/HD

    NARCIS (Netherlands)

    Scheres, A.; Oosterlaan, J.; Swanson, J.; Morein-Zamir, S.; Meiran, N.; Schut, H.; Vlasveld, L.; Sergeant, J.A.

    2003-01-01

    The current study was aimed at (a) investigating the effect of three doses methylphenidate (MPH) and placebo on inhibition of a prepotent response, inhibition of an ongoing response, and interference control in Attention Deficit/Hyperactivity Disorder (AD/HD), and (b) studying dose-response

  2. Response inhibition of face stimuli linked to inferior frontal gyrus microstructure in adolescents

    DEFF Research Database (Denmark)

    Holm-Skjold, Jonathan; Baaré, William Frans Christiaan; Jernigan, Terry Lynne

    matter underlying these regions continues to develop throughout childhood and adolescence, as indicated by in an increase in fractional anisotropy (FA), possibly reflecting ongoing myelination, and/or increase in axon diameter and density7,8. Here we used an emotional Go/Nogo task to test the hypothesis......The ability to inhibit inappropriate behavior is an essential cognitive and social skill. Response inhibition of pre-potent motor responses as measured with a stop-signal or a Go/Nogo task improves throughout adolescence1,2. Performance on these tasks can be modulated by the valence of task stimuli....... Inhibition of negative faces has been shown to be more difficult than that of positive faces1,3. The brain network underlying response inhibition includes the right inferior frontal gyrus (IFG), right presupplementary motor area (preSMA), and superior longitudinal fasciculus (SLF) bilaterally 4–6. The white...

  3. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

    NARCIS (Netherlands)

    Spronk, D.B.; De Bruijn, E.R.; van Wel, J.H.; Ramaekers, J.G.; Verkes, R.J.

    2016-01-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of

  4. Disaster Response and Planning for Libraries.

    Science.gov (United States)

    Kahn, Miriam B.

    Providing a customized disaster response plan to assist libraries in quick recovery, this resource also outlines step to minimize damage and protect materials before trouble strikes. The first section of the book, "Response," contains information how to handle small jobs in-house and suggestions for working with contractors--with an…

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

    Science.gov (United States)

    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…

  6. Learning to inhibit the response during instrumental (operant) extinction.

    Science.gov (United States)

    Bouton, Mark E; Trask, Sydney; Carranza-Jasso, Rodrigo

    2016-07-01

    Five experiments tested implications of the idea that instrumental (operant) extinction involves learning to inhibit the learned response. All experiments used a discriminated operant procedure in which rats were reinforced for lever pressing or chain pulling in the presence of a discriminative stimulus (S), but not in its absence. In Experiment 1, extinction of the response (R) in the presence of S weakened responding in S, but equivalent nonreinforced exposure to S (without the opportunity to make R) did not. Experiment 2 replicated that result and found that extinction of R had no effect on a different R that had also been reinforced in the stimulus. In Experiments 3 and 4, rats first learned to perform several different stimulus and response combinations (S1R1, S2R1, S3R2, and S4R2). Extinction of a response in one stimulus (i.e., S1R1) transferred and weakened the same response, but not a different response, when it was tested in another stimulus (i.e., S2R1 but not S3R2). In Experiment 5, extinction still transferred between S1 and S2 when the stimuli set the occasion for R's association with different types of food pellets. The results confirm the importance of response inhibition in instrumental extinction: Nonreinforcement of the response in S causes the most effective suppression of responding, and response suppression is specific to the response but transfers and influences performance of the same response when it is occasioned by other stimuli. Theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Learning to inhibit the response during instrumental (operant) extinction

    Science.gov (United States)

    Bouton, Mark E.; Trask, Sydney; Carranza-Jasso, Rodrigo

    2016-01-01

    Five experiments tested implications of the idea that instrumental (operant) extinction involves learning to inhibit the learned response. All experiments used a discriminated operant procedure in which rats were reinforced for lever pressing or chain pulling in the presence of a discriminative stimulus (S), but not in its absence. In Experiment 1, extinction of the response (R) in the presence of S weakened responding in S, but equivalent nonreinforced exposure to S (without the opportunity to make R) did not. Experiment 2 replicated that result and found that extinction of R had no effect on a different R that had also been reinforced in the stimulus. In Experiments 3 and 4, rats first learned to perform several different stimulus and response combinations (S1R1, S2R1, S3R2, and S4R2). Extinction of a response in one stimulus (i.e., S1R1) transferred and weakened the same response, but not a different response, when it was tested in another stimulus (i.e., S2R1 but not S3R2). In Experiment 5, extinction still transferred between S1 and S2 when the stimuli set the occasion for R's association with different types of food pellets. The results confirm the importance of response inhibition in instrumental extinction: Nonreinforcement of the response in S causes the most effective suppression of responding, and response suppression is specific to the response but transfers and influences performance of the same response when it is occasioned by other stimuli. Theoretical and practical implications are discussed. PMID:27379715

  8. Gender Responsive Community Based Planning and Budgeting ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... Responsive Community Based Planning and Budgeting Tool for Local Governance ... in data collection, and another module that facilitates gender responsive and ... In partnership with UNESCO's Organization for Women in Science for the ...

  9. Risk analysis in oil spill response planning

    International Nuclear Information System (INIS)

    Chernoplekov, A.N.; Alexandrov, A.A.

    2005-01-01

    Tiered response is a basic approach to emergency plans, including oil spill response (OSR). This paper delineates a huge set of accidental scenarios within a certain tier of response generated by a computer during risk assessment. Parameters such as the amount of oil spilled, duration of discharge and types of losses should be provided in OSR scenarios. Examples of applications include offshore installations, sub sea or onshore pipelines, and localized onshore facilities. The paper demonstrates how to use risk analysis results for delineating all likely spills into groups that need a specific tier response. The best world practices and Russian regulatory approaches were outlined and compared. Corresponding algorithms were developed and their application in pipelines was presented. The algorithm combines expert's skills and spill trajectory modeling with the net environmental benefit analysis principle into the incident specific emergency response planning. 9 refs., 13 tabs., 2 figs

  10. Stimulus-response mappings shape inhibition processes: a combined EEG-fMRI study of contextual stopping.

    Directory of Open Access Journals (Sweden)

    Christina F Lavallee

    Full Text Available Humans are rarely faced with one simple task, but are typically confronted with complex stimulus constellations and varying stimulus-relevance in a given situation. Through modifying the prototypical stop-signal task and by combined recording and analysis of electroencephalography (EEG and functional magnetic resonance imaging (fMRI, we studied the effects of stimulus relevance for the generation of a response or its inhibition. Stimulus response mappings were modified by contextual cues, indicating which of two different stimuli following a go stimulus was relevant for stopping. Overall, response inhibition, that is comparing successful stopping to a stop-signal against go-signal related processes, was associated with increased activity in right inferior and left midfrontal regions, as well as increased EEG delta and theta power; however, stimulus-response conditions in which the most infrequent stop-signal was relevant for inhibition, were associated with decreased activity in regions typically involved in response inhibition, as well as decreased activity in the delta and theta bands as compared to conditions wherein the relevant stop-signal frequency was higher. Behaviorally, this (aforementioned condition, which demanded inhibition only from the most infrequent stimulus, was also associated with reduced reaction times and lower error rates. This pattern of results does not align with typical stimulus frequency-driven findings and suggests interplay between task relevance and stimulus frequency of the stop-signal. Moreover, with a multimodal EEG-fMRI analysis, we demonstrated significant parameterization for response inhibition with delta, theta and beta time-frequency values, which may be interpreted as reflecting conflict monitoring, evaluative and/or motor processes as suggested by previous work (Huster et al., 2013; Aron, 2011. Further multimodal results suggest a possible neurophysiological and behavioral benefit under conditions

  11. Hanford Emergency Response Plan

    International Nuclear Information System (INIS)

    Wagoner, J.D.

    1994-04-01

    The Hanford Emergency Response Plan for the US Department of Energy (DOE), Richland Operations Office (RL), incorporates into one document an overview of the emergency management program for the Hanford Site. The program has been developed in accordance with DOE orders, and state and federal regulations to protect worker and public health and safety and the environment in the event of an emergency at or affecting the Hanford Site. This plan provides a description of how the Hanford Site will implement the provisions of DOE 5500 series and other applicable Orders in terms of overall policies and concept of operations. It should be used as the basis, along with DOE Orders, for the development of specific contractor and RL implementing procedures

  12. Hanford Emergency Response Plan

    Energy Technology Data Exchange (ETDEWEB)

    Wagoner, J.D.

    1994-04-01

    The Hanford Emergency Response Plan for the US Department of Energy (DOE), Richland Operations Office (RL), incorporates into one document an overview of the emergency management program for the Hanford Site. The program has been developed in accordance with DOE orders, and state and federal regulations to protect worker and public health and safety and the environment in the event of an emergency at or affecting the Hanford Site. This plan provides a description of how the Hanford Site will implement the provisions of DOE 5500 series and other applicable Orders in terms of overall policies and concept of operations. It should be used as the basis, along with DOE Orders, for the development of specific contractor and RL implementing procedures.

  13. Response inhibition and impulsive decision-making in sexual offenders against children.

    Science.gov (United States)

    Turner, Daniel; Laier, Christian; Brand, Matthias; Bockshammer, Tamara; Welsch, Robin; Rettenberger, Martin

    2018-05-31

    Current theories view impulsivity as an important factor in the explanation of sexual offending. While impulsivity itself is a multidimensional construct, response inhibition and impulsive decision-making are frequently discussed subcomponents. Impulsivity in sexual offenders could be triggered by sexual cues with high emotional significance. The present study compared response inhibition abilities and the degree of impulsive decision-making between 63 child sexual abusers and 63 nonoffending controls. A Go/No-Go task was used to assess response inhibition, while the Iowa Gambling Task (IGT) and the Game of Dice Task (GDT) were used for the assessment of decision-making. In contrast to previous studies, modified versions of the Go/No-Go task and the IGT were used, including pictures of the Not Real People-Set depicting nude adults and children. Child sexual abusers showed more deficits in response inhibition in the Go/No-Go task. Furthermore, decision-making was especially impaired by the presence of child images in child sexual abusers with more intense pedophilic sexual interests. In contrast, in the nonoffending controls the presence of preferred sexual cues (pictures of women) improved decision-making performance. No differences in overall GDT performance were found between the groups; however, child sexual abusers chose the riskiest option more frequently than nonoffending controls. In line with theoretical assumptions about the processes underlying sexual offending, child sexual abusers show more deficits in neuropsychological functioning, which may be related to more impulsive behaviors. These impairments could be triggered by the presence of sexually relevant cues. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Brain activation for response inhibition under gaming cue distraction in internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Gin-Chung Liu

    2014-01-01

    Full Text Available We evaluated neural substrates related to the loss of control in college students with internet gaming disorder (IGD. We hypothesized that deficit in response inhibition under gaming cue distraction was the possible mechanism for the loss of control internet use. Eleven cases of IGD and 11 controls performed Go/NoGo tasks with/without gaming distraction in the functional magnetic resonance imaging scanner. When the gaming picture was shown as background while individuals were performing Go/NoGo tasks, the IGD group committed more commission errors. The control group increased their brain activations more over the right dorsolateral prefrontal cortex (DLPFC and superior parietal lobe under gaming cue distraction in comparison with the IGD group. Furthermore, brain activation of the right DLPFC and superior parietal lobe were negatively associated with performance of response inhibition among the IGD group. The results suggest that the function of response inhibition was impaired under gaming distraction among the IGD group, and individuals with IGD could not activate right DLPFC and superior parietal lobe to keep cognitive control and attention allocation for response inhibition under gaming cue distraction. This mechanism should be addressed in any intervention for IGD.

  15. Altered neural connectivity during response inhibition in adolescents with attention-deficit/hyperactivity disorder and their unaffected siblings.

    Science.gov (United States)

    van Rooij, Daan; Hartman, Catharina A; Mennes, Maarten; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Heslenfeld, Dirk; Faraone, Stephen V; Buitelaar, Jan K; Hoekstra, Pieter J

    2015-01-01

    Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates that altered functional and structural neural connectivity are part of the neurobiological basis of ADHD. Here, we investigated if adolescents with ADHD show altered functional connectivity during response inhibition compared to their unaffected siblings and healthy controls. Response inhibition was assessed using the stop signal paradigm. Functional connectivity was assessed using psycho-physiological interaction analyses applied to BOLD time courses from seed regions within inferior- and superior frontal nodes of the response inhibition network. Resulting networks were compared between adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and controls (N = 125). Control subjects showed stronger functional connectivity than the other two groups within the response inhibition network, while subjects with ADHD showed relatively stronger connectivity between default mode network (DMN) nodes. Stronger connectivity within the response inhibition network was correlated with lower ADHD severity, while stronger connectivity with the DMN was correlated with increased ADHD severity. Siblings showed connectivity patterns similar to controls during successful inhibition and to ADHD subjects during failed inhibition. Additionally, siblings showed decreased connectivity with the primary motor areas as compared to both participants with ADHD and controls. Subjects with ADHD fail to integrate activation within the response inhibition network and to inhibit connectivity with task-irrelevant regions. Unaffected siblings show similar alterations only during failed stop trials, as well as unique suppression of motor areas, suggesting compensatory strategies. These findings support the role of altered functional connectivity in understanding the neurobiology and familial transmission of ADHD.

  16. Separating intentional inhibition of prepotent responses and resistance to proactive interference in alcohol-dependent individuals.

    Science.gov (United States)

    Noël, Xavier; Van der Linden, Martial; Brevers, Damien; Campanella, Salvatore; Verbanck, Paul; Hanak, Catherine; Kornreich, Charles; Verbruggen, Frederick

    2013-03-01

    Impulsivity is a hallmark of addictive behaviors. Addicts' weakened inhibition of irrelevant prepotent responses is commonly thought to explain this association. However, inhibition is not a unitary mechanism. This study investigated the efficiency of overcoming competition due to irrelevant responses (i.e., inhibition of a prepotent response) and overcoming competition in memory (i.e., resistance to proactive interference) in sober and recently detoxified alcohol-dependent individuals. Three cognitive tasks assessing the inhibition of a prepotent response (Hayling task, anti-saccade task and Stroop task) and two tasks tapping into the capacity to resist proactive interference (cued recall, Brown-Peterson variant) were administered to 30 non-amnesic recently detoxified alcohol-dependent individuals and 30 matched healthy participants without alcohol dependency. In addition, possible confounds such as verbal updating in working memory was assessed. Alcohol-dependent subjects performed worse than healthy participants on the three cognitive tasks assessing the inhibition of irrelevant prepotent responses but group performance was similar in the tasks assessing overcoming proactive interference in memory, updating of working memory and abstract reasoning. These findings suggest that alcohol-dependence is mainly associated with impaired capacity to intentionally suppress irrelevant prepotent response information. Control of proactive interference from memory is preserved. Theoretical and clinical implications are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Sites Requiring Facility Response Plans, Geographic NAD83, EPA (2006) [facility_response_plan_sites_la_EPA_2007

    Data.gov (United States)

    Louisiana Geographic Information Center — Locations of facilities in Louisiana requiring Oil Pollution Act (OPA) Facility Response Plans (FRP). The dataset was provided by the Region 6 OSCARS program....

  18. Metformin inhibits inflammatory response via AMPK–PTEN pathway in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Kim, Sun Ae; Choi, Hyoung Chul

    2012-01-01

    Highlights: ► PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. ► Metformin suppressed TNF-α-induced COX-2 and iNOS mRNA expression. ► Compound C and bpv (pic) increased iNOS and COX-2 protein expression. ► NF-κB activation was restored by inhibiting AMPK and PTEN. ► AMPK and PTEN regulated TNF-α-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK–PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 μM) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-α) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-κB. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-κB activation decreased in response to metformin and was restored by inhibiting AMPK and PTEN. Inhibiting AMPK and PTEN restored ROS levels stimulated with TNF-α. Taken together, PTEN could be a possible downstream regulator of AMPK, and the

  19. Oil spill response planning under the Oil Pollution Act of 1990

    International Nuclear Information System (INIS)

    Lees, J.E.

    1992-01-01

    The oil spill in Alaska's Prince William Sound on March 24, 1989 illustrated the need for more resources, better planning, and better command and control to efficiently and effectively respond to, contain and cleanup catastrophic oil spills. In response to public concern and industry initiatives to resolve existing oil spill response problems. Congress enacted the comprehensive Oil Pollution Act of 1990 (OPA-90) on August 18, 1990. OPA-90 mandates comprehensive changes in vessel and facility response planning, envisioning a comprehensive and integrated oil spill response planning scheme, with revisions to reflect OPA-90's new requirements. Area Committees comprised of federal, state and local officials and others will prepare Area Contingency Plans for Coast Guard approval, which set forth the framework for responding to open-quotes worst case dischargesclose quotes. Owners and operators of tank vessels and onshore and offshore facilities must submit individual response plans for federal approval by February 18, 1993, identifying and ensuring availability of private personnel and equipment necessary to remove to the maximum extent practicable a open-quotes worst case discharge.close quotes The Coast Guard is considering rules to implement these requirements. Major challenges exist to meet the statutory requirements, including response times, skimming efficiencies, adverse weather and others that affect emergency response capability. This paper focuses on: (1) oil spill response problems identified and lessons learned from the Prince William Sound spill; (2) OPA-90's complex and technical oil spill response planning requirements and their effect on response planning for marine operations; (3) the federal regulatory program to implement OPA-90, defining spill response capability for a open-quotes worst case discharge,close quotes considering existing response resources and the new capabilities by the industry-supported Marine Spill Response Corporation

  20. Neural Correlates of Rewarded Response Inhibition in Youth at Risk for Problematic Alcohol Use

    Directory of Open Access Journals (Sweden)

    Brenden Tervo-Clemmens

    2017-11-01

    Full Text Available Risk for substance use disorder (SUD is associated with poor response inhibition and heightened reward sensitivity. During adolescence, incentives improve performance on response inhibition tasks and increase recruitment of cortical control areas (Geier et al., 2010 associated with SUD (Chung et al., 2011. However, it is unknown whether incentives moderate the relationship between response inhibition and trait-level psychopathology and personality features of substance use risk. We examined these associations in the current project using a rewarded antisaccade (AS task (Geier et al., 2010 in youth at risk for substance use. Participants were 116 adolescents and young adults (ages 12–21 from the University of Pittsburgh site of the National Consortium on Adolescent Neurodevelopment and Alcohol [NCANDA] study, with neuroimaging data collected at baseline and 1 year follow up visits. Building upon previous work using this task in normative developmental samples (Geier et al., 2010 and adolescents with SUD (Chung et al., 2011, we examined both trial-wise BOLD responses and those associated with individual task-epochs (cue presentation, response preparation, and response and associated them with multiple substance use risk factors (externalizing and internalizing psychopathology, family history of substance use, and trait impulsivity. Results showed that externalizing psychopathology and high levels of trait impulsivity (positive urgency, SUPPS-P were associated with general decreases in antisaccade performance. Accompanying this main effect of poor performance, positive urgency was associated with reduced recruitment of the frontal eye fields (FEF and inferior frontal gyrus (IFG in both a priori regions of interest and at the voxelwise level. Consistent with previous work, monetary incentive improved antisaccade behavioral performance and was associated with increased activation in the striatum and cortical control areas. However, incentives did

  1. Federal, provincial and territorial public health response plan for biological events.

    Science.gov (United States)

    McNeill, R; Topping, J

    2018-01-04

    The Federal/Provincial/Territorial (FPT) Public Health Response Plan for Biological Events was developed for the Public Health Network Council (PHNC). This plan outlines how the national response to public health events caused by biological agents will be conducted and coordinated, with a focus on implementation of responses led by senior-level FPT public health decision-makers. The plan was developed by an expert task group and was approved by PHNC in October, 2017. The plan describes roles, responsibilities and authorities of FPT governments for public health and emergency management, a concept of operations outlining four scalable response levels and a governance structure that aims to facilitate an efficient, timely, evidence-informed and consistent approach across jurisdictions. Improving effective engagement amongst public health, health care delivery and health emergency management authorities is a key objective of the plan.

  2. On the automaticity of response inhibition in individuals with alcoholism.

    Science.gov (United States)

    Noël, Xavier; Brevers, Damien; Hanak, Catherine; Kornreich, Charles; Verbanck, Paul; Verbruggen, Frederick

    2016-06-01

    Response inhibition is usually considered a hallmark of executive control. However, recent work indicates that stop performance can become associatively mediated ('automatic') over practice. This study investigated automatic response inhibition in sober and recently detoxified individuals with alcoholism.. We administered to forty recently detoxified alcoholics and forty healthy participants a modified stop-signal task that consisted of a training phase in which a subset of the stimuli was consistently associated with stopping or going, and a test phase in which this mapping was reversed. In the training phase, stop performance improved for the consistent stop stimuli, compared with control stimuli that were not associated with going or stopping. In the test phase, go performance tended to be impaired for old stop stimuli. Combined, these findings support the automatic inhibition hypothesis. Importantly, performance was similar in both groups, which indicates that automatic inhibitory control develops normally in individuals with alcoholism.. This finding is specific to individuals with alcoholism without other psychiatric disorders, which is rather atypical and prevents generalization. Personalized stimuli with a stronger affective content should be used in future studies. These results advance our understanding of behavioral inhibition in individuals with alcoholism. Furthermore, intact automatic inhibitory control may be an important element of successful cognitive remediation of addictive behaviors.. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Hot or not: Response inhibition reduces the hedonic value and motivational incentive of sexual stimuli

    Directory of Open Access Journals (Sweden)

    Anne E. Ferrey

    2012-12-01

    Full Text Available The motivational incentive of reward-related stimuli can become so salient that it drives behavior at the cost of other needs. Here we show that response inhibition applied during a Go/No-go task not only impacts hedonic evaluations but also reduces the behavioral incentive of motivationally-relevant stimuli. We first examined the impact of response inhibition on the hedonic value of sex stimuli associated with strong behavioral-approach responses (Experiment 1. Sexually-appealing and non-appealing images were both rated as less attractive when previously encountered as No-go (inhibited than as Go (non-inhibited items. We then discovered that inhibition reduces the motivational incentive of sexual appealing stimuli (Experiment 2. Prior Go/No-go status affected the number of key-presses by heterosexual males to view erotic-female (sexually-appealing but not erotic-male or scrambled-control (non-appealing images. These findings may provide an important foundation for developing inhibition-based interventions to reduce the hedonic value and motivational incentive of stimuli associated with disorders of self-control.

  4. Hot or Not: Response Inhibition Reduces the Hedonic Value and Motivational Incentive of Sexual Stimuli

    Science.gov (United States)

    Ferrey, Anne E.; Frischen, Alexandra; Fenske, Mark J.

    2012-01-01

    The motivational incentive of reward-related stimuli can become so salient that it drives behavior at the cost of other needs. Here we show that response inhibition applied during a Go/No-go task not only impacts hedonic evaluations but also reduces the behavioral incentive of motivationally relevant stimuli. We first examined the impact of response inhibition on the hedonic value of sex stimuli associated with strong behavioral-approach responses (Experiment 1). Sexually appealing and non-appealing images were both rated as less attractive when previously encountered as No-go (inhibited) than as Go (non-inhibited) items. We then discovered that inhibition reduces the motivational incentive of sexual appealing stimuli (Experiment 2). Prior Go/No-go status affected the number of key-presses by heterosexual males to view erotic-female (sexually appealing) but not erotic-male or scrambled-control (non-appealing) images. These findings may provide a foundation for developing inhibition-based interventions to reduce the hedonic value and motivational incentive of stimuli associated with disorders of self-control. PMID:23272002

  5. Cyperus scariosus Chloroform Fraction Inhibits T cell Responses in ...

    African Journals Online (AJOL)

    Erah

    CSC did not significantly (p < 0.01) suppress Th2 (IL-4) system. Conclusion: The findings from this investigation reveal that C. scariosus causes immunosuppression by inhibiting Th1 cytokines. Keywords: Cyperus scariosus; Immunosuppression; Humoral antibody titre; Cell-mediated immune response; CD 4+ T- helper cells ...

  6. Emergency response planning and preparedness for transport accidents involving radioactive material

    International Nuclear Information System (INIS)

    1988-01-01

    The purpose of this Guide is to provide assistance to public authorities and others (including consignors and carriers of radioactive materials) who are responsible for ensuring safety in establishing and developing emergency response arrangements for responding effectively to transport accidents involving radioactive materials. This Guide is concerned mainly with the preparation of emergency response plans. It provides information which will assist those countries whose involvement with radioactive materials is just beginning and those which have already developed their industries involving radioactive materials and attendant emergency plans, but may need to review and improve these plans. The need for emergency response plans and the ways in which they are implemented vary from country to country. In each country, the responsible authorities must decide how best to apply this Guide, taking into account the actual shipments and associated hazards. In this Guide the emergency response planning and response philosophy are outlined, including identification of emergency response organizations and emergency services that would be required during a transport accident. General consequences which could prevail during an accident are described taking into account the IAEA Regulations for the Safe Transport of Radioactive Material. 43 refs, figs and tabs

  7. Anterior cingulate serotonin 1B receptor binding is associated with emotional response inhibition

    DEFF Research Database (Denmark)

    da Cunha-Bang, Sofi; Hjordt, Liv Vadskjær; Dam, Vibeke Høyrup

    2017-01-01

    -offender controls, completed an emotional Go/NoGo task requiring inhibition of prepotent motor responses to emotional facial expressions. We also measured cerebral serotonin 1B receptor (5-HT1BR) binding with [11C]AZ10419369 positron emission tomography within regions of the frontal cortex. We hypothesized that 5......-HT1BR would be positively associated with false alarms (failures to inhibit nogo responses) in the context of aversive (angry and fearful) facial expressions. Across groups, we found that frontal cortex 5-HT1BR binding was positively correlated with false alarms when angry faces were go stimuli......Serotonin has a well-established role in emotional processing and is a key neurotransmitter in impulsive aggression, presumably by facilitating response inhibition and regulating subcortical reactivity to aversive stimuli. In this study 44 men, of whom 19 were violent offenders and 25 were non...

  8. Response Inhibition in Adults and Teenagers: Spatiotemporal Differences in the Prefrontal Cortex

    Science.gov (United States)

    Vidal, Julie; Mills, Travis; Pang, Elizabeth W.; Taylor, Margot J.

    2012-01-01

    Inhibition is a core executive function reliant on the frontal lobes that shows protracted maturation through to adulthood. We investigated the spatiotemporal characteristics of response inhibition during a visual go/no-go task in 14 teenagers and 14 adults using magnetoencephalography (MEG) and a contrast between two no-go experimental conditions…

  9. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

    Directory of Open Access Journals (Sweden)

    Geneviève Pèépin

    2017-10-01

    Full Text Available Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1 by low-dose camptothecin (CPT can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40 large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development.

  10. Periostin Limits Tumor Response to VEGFA Inhibition

    Directory of Open Access Journals (Sweden)

    Ioanna Keklikoglou

    2018-03-01

    Full Text Available Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs under extended vascular-endothelial growth factor A (VEGFA blockade are dependent on periostin (POSTN, a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA+ stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2, an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs.

  11. LYATK1 potently inhibits LPS-mediated pro-inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Feng [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China); Liu, Yuan [Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, Nanjing (China); Wang, Xiujuan; Kong, Wei [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China); Zhao, Feng, E-mail: taixingzhaofeng163@163.com [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China)

    2016-01-29

    Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory cytokines, which could lead to endotoxin shock. TGF-β-activated kinase1 (TAK1) activation is involved in the process. In the current study, we studied the potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited LPS-induced mRNA expression and production of several pro-inflammatory cytokines [interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced pro-inflammatory cytokine production was again attenuated with LYTAK1 co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (Erk, Jnk and p38) activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFκB-p38 in ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. Together, these results demonstrate that LYTAK1 inhibits LPS-induced production of several pro-inflammatory cytokines and endotoxin shock probably through blocking TAK1-regulated signalings. - Highlights: • LYTAK1 inhibits LPS-induced pro-inflammatory cytokine production in RAW 264.7 cells. • The effect by LYTAK1 is more potent than other known TAK1 inhibitors. • LYTAK1 inhibits LPS-induced cytokine production in primary macrophages/monocytes. • LYTAK1 inhibits LPS-induced TAK1-NFκB and MAPK activation in macrophages/monocytes. • LYTAK1 gavage inhibits LPS-induced endotoxin shock and cytokine production in mice.

  12. LYATK1 potently inhibits LPS-mediated pro-inflammatory response

    International Nuclear Information System (INIS)

    Xi, Feng; Liu, Yuan; Wang, Xiujuan; Kong, Wei; Zhao, Feng

    2016-01-01

    Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory cytokines, which could lead to endotoxin shock. TGF-β-activated kinase1 (TAK1) activation is involved in the process. In the current study, we studied the potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited LPS-induced mRNA expression and production of several pro-inflammatory cytokines [interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced pro-inflammatory cytokine production was again attenuated with LYTAK1 co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (Erk, Jnk and p38) activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFκB-p38 in ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. Together, these results demonstrate that LYTAK1 inhibits LPS-induced production of several pro-inflammatory cytokines and endotoxin shock probably through blocking TAK1-regulated signalings. - Highlights: • LYTAK1 inhibits LPS-induced pro-inflammatory cytokine production in RAW 264.7 cells. • The effect by LYTAK1 is more potent than other known TAK1 inhibitors. • LYTAK1 inhibits LPS-induced cytokine production in primary macrophages/monocytes. • LYTAK1 inhibits LPS-induced TAK1-NFκB and MAPK activation in macrophages/monocytes. • LYTAK1 gavage inhibits LPS-induced endotoxin shock and cytokine production in mice.

  13. ACE polymorphism does not determine short-term renal response to ACE-inhibition in proteinuric patients

    NARCIS (Netherlands)

    vanderKleij, FGH; Navis, GJ; Gansevoort, RT; Scheffer, H; deZeeuw, D; deJong, PE

    1997-01-01

    Background. The renal response to ACE inhibition is known to vary between individuals. The ACE genotype is a determinant of the ACE concentrations in plasma and tissue, and therefore might affect the renal response to ACE inhibition in renal patients. Methods. To test this hypothesis we studied the

  14. Development of response inhibition in the context of relevant versus irrelevant emotions

    Directory of Open Access Journals (Sweden)

    Margot A Schel

    2013-07-01

    Full Text Available The present study examined the influence of relevant and irrelevant emotions on response inhibition from childhood to early adulthood. Ninety-four participants between 6 and 25 years of age performed two go/nogo tasks with emotional faces (neutral, happy, and fearful as stimuli. In one go/nogo task emotion formed a relevant dimension of the task and in the other go/nogo task emotion was irrelevant and participants had to respond to the color of the faces instead. A special feature of the latter task, in which emotion was irrelevant, was the inclusion of free choice trials, in which participants could freely decide between acting and inhibiting. Results showed a linear increase in response inhibition performance with increasing age both in relevant and irrelevant affective contexts. Relevant emotions had a pronounced influence on performance across age, whereas irrelevant emotions did not. Overall, participants made more false alarms on trials with fearful faces than happy faces, and happy faces were associated with better performance on go trials (higher percentage correct and faster RTs than fearful faces. The latter effect was stronger for young children in terms of accuracy. Finally, during the free choice trials participants did not base their decisions on affective context, confirming that irrelevant emotions do not have a strong impact on inhibition. Together, these findings suggest that across development relevant affective context has a larger influence on response inhibition than irrelevant affective context. When emotions are relevant, a context of positive emotions is associated with better performance compared to a context with negative emotions, especially in young children.

  15. Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.

    Science.gov (United States)

    Robertson, Chelsea L; Ishibashi, Kenji; Mandelkern, Mark A; Brown, Amira K; Ghahremani, Dara G; Sabb, Fred; Bilder, Robert; Cannon, Tyrone; Borg, Jacqueline; London, Edythe D

    2015-04-15

    Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. Copyright © 2015 the authors 0270-6474/15/355990-08$15.00/0.

  16. The One Plan Project: A cooperative effort of the National Response Team and the Region 6 Regional Response Team to simplify facility emergency response planning

    International Nuclear Information System (INIS)

    Staves, J.; McCormick, K.

    1997-01-01

    The National Response Team (NRT) in coordination with the Region 6 Response Team (RRT) have developed a facility contingency plan format which would integrate all existing regulatory requirements for contingency planning. This format was developed by a multi-agency team, chaired by the USEPA Region 6, in conjunction with various industry, labor, and public interest groups. The impetus for this project came through the USEPA Office of Chemical Emergency Preparedness and Prevention (CEPPO). The current national oil and hazardous material emergency preparedness and response system is an amalgam of federal, state, local, and industrial programs which are often poorly coordinated. In a cooperative effort with the NRT, the CEPPO conducted a Presidential Review of federal agency authorities and coordination responsibilities regarding release prevention, mitigation, and response. Review recommendations led to a Pilot Project in USEPA Region 6. The Region 6 Pilot Project targeted end users in the intensely industrialized Houston Ship Channel (HSC) area, which is comprised of petroleum and petrochemical companies

  17. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ae [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. Black-Right-Pointing-Pointer Metformin suppressed TNF-{alpha}-induced COX-2 and iNOS mRNA expression. Black-Right-Pointing-Pointer Compound C and bpv (pic) increased iNOS and COX-2 protein expression. Black-Right-Pointing-Pointer NF-{kappa}B activation was restored by inhibiting AMPK and PTEN. Black-Right-Pointing-Pointer AMPK and PTEN regulated TNF-{alpha}-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 {mu}M) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-{alpha}) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-{kappa}B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-{kappa}B activation decreased in response to metformin and was restored by inhibiting AMPK

  18. Within-Subject Correlation Analysis to Detect Functional Areas Associated With Response Inhibition

    Directory of Open Access Journals (Sweden)

    Tomoko Yamasaki

    2018-05-01

    Full Text Available Functional areas in fMRI studies are often detected by brain-behavior correlation, calculating across-subject correlation between the behavioral index and the brain activity related to a function of interest. Within-subject correlation analysis is also employed in a single subject level, which utilizes cognitive fluctuations in a shorter time period by correlating the behavioral index with the brain activity across trials. In the present study, the within-subject analysis was applied to the stop-signal task, a standard task to probe response inhibition, where efficiency of response inhibition can be evaluated by the stop-signal reaction time (SSRT. Since the SSRT is estimated, by definition, not in a trial basis but from pooled trials, the correlation across runs was calculated between the SSRT and the brain activity related to response inhibition. The within-subject correlation revealed negative correlations in the anterior cingulate cortex and the cerebellum. Moreover, the dissociation pattern was observed in the within-subject analysis when earlier vs. later parts of the runs were analyzed: negative correlation was dominant in earlier runs, whereas positive correlation was dominant in later runs. Regions of interest analyses revealed that the negative correlation in the anterior cingulate cortex, but not in the cerebellum, was dominant in earlier runs, suggesting multiple mechanisms associated with inhibitory processes that fluctuate on a run-by-run basis. These results indicate that the within-subject analysis compliments the across-subject analysis by highlighting different aspects of cognitive/affective processes related to response inhibition.

  19. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  20. Sensory and cross-network contributions to response inhibition in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Matthew J. Hoptman

    Full Text Available Patients with schizophrenia show response inhibition deficits equal to or greater than those seen in impulse-control disorders, and these deficits contribute to poor outcome. However, little is known about the circuit abnormalities underlying this impairment. To address this, we examined stop signal task performance in 21 patients with schizophrenia and 21 healthy controls using event related potential (ERP and resting state functional connectivity. Patients showed prolonged stop signal reaction time (SSRT and reduced N1, N2, and P3 amplitudes compared to controls. Across groups, P3 amplitudes were maximal after SSRT (i.e., after the time associated with the decision to stop occurred, suggesting that this component indexed response monitoring. Multiple regression analyses showed that longer SSRTs were independently related to 1 patient status, 2 reduced N1 amplitude on successful stop trials and 3 reduced anticorrelated resting state functional connectivity between visual and frontoparietal cortical networks. This study used a combined multimodal imaging approach to better understand the network abnormalities that underlie response inhibition in schizophrenia. It is the first of its kind to specifically assess the brain's resting state functional architecture in combination with behavioral and ERP methods to investigate response inhibition in schizophrenia. Keywords: EEG, Stop signal task, Impulsivity, Schizophrenia, Resting state functional connectivity

  1. Transformation Planning of Ecotourism Systems to Invigorate Responsible Tourism

    Directory of Open Access Journals (Sweden)

    Yun Eui Choi

    2017-12-01

    Full Text Available The purpose of this study is to introduce transformation plans that can stimulate responsible ecotourism by using systems thinking to solve ecotourism problems in Korea. Systems thinking is a research method used to understand the operating mechanisms of the variables that influence an entire system, in order to identify its problems. The four types of ecotourism systems are classified as follows: low-infrastructure and resident-initiated, high-infrastructure and resident-initiated, high-infrastructure and government-initiated and low-infrastructure and government-initiated. These systems vary based on the need for tourism facilities and the form of governance. Each type of system is analyzed using the systems thinking process (dynamic thinking, causal thinking, feedback thinking, strategic thinking at representative ecotourism sites in Jeollanam-do and the following transformation plans are proposed to improve the responsibility at the tourism sites: First, local residents will develop a system to manage and operate ecotourism ventures and establish cooperative governance structures to strengthen the local capacity. Second, ecotourism operators will improve the quality of their educational and interpretative programs and tourist information platforms in order to raise awareness of the responsibilities of ecotourists. Third, ecotourism systems that are improved through ecotourists’ and tour operators' heightened senses of responsibility can sustain ecotourism independently. These transformation plans can be applied to policy proposals for revitalizing ecotourism, to guidelines for improving community resilience and to biological habitat protection plans. This study is meaningful in that it discusses the role of stakeholders in ecotourism planning and promoting responsible tourism and their role in utilizing and conserving natural resources accordingly.

  2. Heritability of brain activity related to response inhibition: a longitudinal genetic study in adolescent twins

    Science.gov (United States)

    Anokhin, Andrey P.; Golosheykin, Simon; Grant, Julia D.; Heath, Andrew C.

    2017-01-01

    The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. PMID:28300615

  3. Differential modulation of the N2 and P3 event-related potentials by response conflict and inhibition.

    Science.gov (United States)

    Groom, Madeleine J; Cragg, Lucy

    2015-07-01

    Developing reliable and specific neural markers of cognitive processes is essential to improve understanding of healthy and atypical brain function. Despite extensive research there remains uncertainty as to whether two electrophysiological markers of cognitive control, the N2 and P3, are better conceptualised as markers of response inhibition or response conflict. The present study aimed to directly compare the effects of response inhibition and response conflict on the N2 and P3 event-related potentials, within-subjects. A novel hybrid go/no-go flanker task was performed by 19 healthy adults aged 18-25 years while EEG data were collected. The response congruence of a central target stimulus and 4 flanking stimuli was manipulated between trials to vary the degree of response conflict. Response inhibition was required on a proportion of trials. N2 amplitude was measured at two frontal electrode sites; P3 amplitude was measured at 4 midline electrode sites. N2 amplitude was greater on incongruent than congruent trials but was not enhanced by response inhibition when the stimulus array was congruent. P3 amplitude was greater on trials requiring response inhibition; this effect was more pronounced at frontal electrodes. P3 amplitude was also enhanced on incongruent compared with congruent trials. The findings support a role for N2 amplitude as a marker of response conflict and for the frontal shift of the P3 as a marker of response inhibition. This paradigm could be applied to clinical groups to help clarify the precise nature of impaired action control in disorders such as attention deficit/hyperactivity disorders (ADHD). Copyright © 2015 Elsevier Inc. All rights reserved.

  4. The implementation of the IAEA accident response plan in Yugoslav practice

    International Nuclear Information System (INIS)

    Orlic, M.; Pavlovic, R.; Markovic, S.; Pavlovic, S.

    1996-01-01

    One of the important lessons from the Chernobyl accident is the necessity of existence of operational national emergency response plan. Summarizing consequences and experiences after Chernobyl accident, expert groups from IAEA, ICRP and other international scientific organizations, have been extensively worked on reviewing old ones, and preparing new radiation protection and nuclear safety principals and codes. One of the important issue is national emergency response plan for radiological accident. The nuclear accident response plan in Yugoslavia is presented in this paper. It is essentially based on IAEA model national response plan for radiological accident. This model has to be adjusted to the specificity of member states. The optimum society organization for emergency management in the case of accidents in ionizing radiation sources practices is suggested in this paper. Specific characteriztics of Yugoslav state organization relating to accident response are emphasised. (author)

  5. Radiological emergency response planning in Pennsylvania

    International Nuclear Information System (INIS)

    Henderson, O.K.

    1981-01-01

    The most important aspect of emergency preparedness is to recognize and accept the fact that there exists a potential for a problem or a condition and that it requires some attention. Emergency plans should be sufficiently flexible so as to accommodate the emergency situation as it unfolds. Of the several emergency responses that may be taken following a nuclear power plant accident evacuation evokes the greatest attention and discussion as to whether it is truly a feasible option. Movements of people confined to mass care facilities or on life support systems involve special requirements. The Three Mile Island accident has been the most studied nuclear incident in the history of the nuclear power reactor industry. The findings of these reports will have a major influence on nuclear power issues as they are addressed in the future. The question remains as to whether the political leadership will be willing to provide the resources required by the emergency plan. Future safety and emergency response to nuclear accidents depend upon Government and industry acting responsibly and not merely responding to regulations. The Three Mile Island accident has had some beneficial side effects for the emergency management community. It has: increased the level of awareness and importance of emergency planning; served as a catalyst for the sharing of experiences and information; encouraged standardization of procedures; and emphasized the need for identifying and assigning responsibilities. The Emergency Management Organization in responding to a disaster situation does not enjoy the luxury of time. It needs to act decisively and correctly. It does not often get a second chance. Governments, at all levels, and the nuclear power industry have been put on notice as a result of Three Mile Island. The future of nuclear energy may well hang in the balance, based upon the public's perception of the adequacy of preparedness and safety measures being taken. (author)

  6. Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

    Science.gov (United States)

    Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

    2017-02-01

    Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

  7. On the need for a national radiological response plan in Egypt

    International Nuclear Information System (INIS)

    Gant, K.D.; Salama, M.; Ghani, A.H.A.; Sharnouby, A.E.; Hamouda, I.

    1997-01-01

    Use of radioactive materials and sources is increasing within the Arab Republic of Egypt. With this increase comes a need to prepare for accidents involving these materials. For years there has been an informal agreement between the National Centre for Nuclear Safety and Radiation Control (NCNSRC), one of the four centers operated by the Atomic Energy Agency (AEA), and the Civil Defense Authority (CDA) to cooperate in a radiological emergency. CDA currently has the responsibility for responding to all types of emergencies. The increasing use of radioactive materials and the complexity of the response required by accidents creates a need for a more formal arrangement. In response to the increasing possibility of radiation accidents in or near Egypt, the government is preparing the Egyptian Emergency Response Plan for Radiological Accidents to coordinate the response efforts of the national agencies. This plan, which is now being finalized, provides information on agency roles and responsibilities during a response. The plan will also provide a basis for initiating training, planning for emergency public information, and developing public education efforts

  8. Response inhibition and cognitive appraisal in clients with acute stress disorder and posttraumatic stress disorder.

    Science.gov (United States)

    Abolghasemi, Abass; Bakhshian, Fereshteh; Narimani, Mohammad

    2013-08-01

    The purpose of the present study was to compare response inhibition and cognitive appraisal in clients with acute stress disorder, clients with posttraumatic stress disorder, and normal individuals. This was a comparative study. The sample consisted of 40 clients with acute stress disorder, 40 patients with posttraumatic stress disorder, and 40 normal individuals from Mazandaran province selected through convenience sampling method. Data were collected using Composite International Diagnostic Interview, Stroop Color-Word Test, Posttraumatic Cognitions Inventory, and the Impact of Event Scale. Results showed that individuals with acute stress disorder are less able to inhibit inappropriate responses and have more impaired cognitive appraisals compared to those with posttraumatic stress disorder. Moreover, results showed that response inhibition and cognitive appraisal explain 75% of the variance in posttraumatic stress disorder symptoms and 38% of the variance in posttraumatic stress disorder symptoms. The findings suggest that response inhibition and cognitive appraisal are two variables that influence the severity of posttraumatic stress disorder and acute stress disorder symptoms. Also, these results have important implications for pathology, prevention, and treatment of posttraumatic stress disorder and acute stress disorder.

  9. RE-PLAN: An Extensible Software Architecture to Facilitate Disaster Response Planning

    Science.gov (United States)

    O’Neill, Martin; Mikler, Armin R.; Indrakanti, Saratchandra; Tiwari, Chetan; Jimenez, Tamara

    2014-01-01

    Computational tools are needed to make data-driven disaster mitigation planning accessible to planners and policymakers without the need for programming or GIS expertise. To address this problem, we have created modules to facilitate quantitative analyses pertinent to a variety of different disaster scenarios. These modules, which comprise the REsponse PLan ANalyzer (RE-PLAN) framework, may be used to create tools for specific disaster scenarios that allow planners to harness large amounts of disparate data and execute computational models through a point-and-click interface. Bio-E, a user-friendly tool built using this framework, was designed to develop and analyze the feasibility of ad hoc clinics for treating populations following a biological emergency event. In this article, the design and implementation of the RE-PLAN framework are described, and the functionality of the modules used in the Bio-E biological emergency mitigation tool are demonstrated. PMID:25419503

  10. Radioactive materials transportation emergency response plan

    International Nuclear Information System (INIS)

    Karmali, N.

    1987-05-01

    Ontario Hydro transports radioactive material between its nuclear facilities, Atomic Energy of Canada Limited at Chalk River Laboratories and Radiochemical Company in Kanata, on a regular basis. Ontario Hydro also occasionally transports to Whiteshell Laboratories, Hydro-Quebec and New Brunswick Electric Power Commission. Although there are stringent packaging and procedural requirements for these shipments, Ontario Hydro has developed a Radioactive Materials Transportation Emergency Response Plan in the event that there is an accident. The Transportation Emergency Response plan is based on six concepts: 1) the Province id divided into three response areas with each station (Pickering, Darlington, Bruce) having identified response areas; 2) response is activated via a toll-free number. A shift supervisor at Pickering will answer the call, determine the hazards involved from the central shipment log and provide on-line advice to the emergency worker. At the same time he will notify the nearest Ontario Hydro area office to provide initial corporate response, and will request the nearest nuclear station to provide response assistance; 3) all stations have capability in terms of trained personnel and equipment to respond to an accident; 4) all Ontario Hydro shipments are logged with Pickering NGS. Present capability is based on computerized logging with the computer located in the shift office at Pickering to allow quick access to information on the shipment; 5) there is a three tier structure for emergency public information. The local Area Manager is the first Ontario Hydro person at the scene of the accident. The responding facility technical spokesperson is the second line of Corporate presence and the Ontario Hydro Corporate spokesperson is notified in case the accident is a media event; and 6) Ontario Hydro will respond to non-Hydro shipments of radioactive materials in terms of providing assistance, guidance and capability. However, the shipper is responsible

  11. Action plan in response to March 1981 report to NFPQT Committee

    International Nuclear Information System (INIS)

    1981-03-01

    This plan of action has been prepared at the direction of the Acting Under Secretary in response to the report of the Nuclear Facilities Personnel Qualifications and Training (NFPQT) Committee on A Safety Assessment of Department of Energy Nuclear Reactors. Senior Department officials with Headquarters responsibilities for the safety of nuclear facilities owned by and operated for the Department have developed this plan with input from the operations office managers having operational responsibility for such facilities. A summary of the plan's objectives and a cross-reference to the findings of the NFPQT Committee Report is attached to the plan. Appendix A contains implementing actions and Appendix B contains a summary of actions responsive to lessons learned from the TMI accident that have been completed or are well underway. Although the plan is written in definitive language, the specific actions (such as organization realignments and proposals) will be subject to appropriate review and approval. Also, other adjustments may be required as the actions are implemented

  12. TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer.

    Science.gov (United States)

    Gong, Ke; Guo, Gao; Gerber, David E; Gao, Boning; Peyton, Michael; Huang, Chun; Minna, John D; Hatanpaa, Kimmo J; Kernstine, Kemp; Cai, Ling; Xie, Yang; Zhu, Hong; Fattah, Farjana J; Zhang, Shanrong; Takahashi, Masaya; Mukherjee, Bipasha; Burma, Sandeep; Dowell, Jonathan; Dao, Kathryn; Papadimitrakopoulou, Vassiliki A; Olivas, Victor; Bivona, Trever G; Zhao, Dawen; Habib, Amyn A

    2018-06-01

    Although aberrant EGFR signaling is widespread in cancer, EGFR inhibition is effective only in a subset of non-small cell lung cancer (NSCLC) with EGFR activating mutations. A majority of NSCLCs express EGFR wild type (EGFRwt) and do not respond to EGFR inhibition. TNF is a major mediator of inflammation-induced cancer. We find that a rapid increase in TNF level is a universal adaptive response to EGFR inhibition in NSCLC, regardless of EGFR status. EGFR signaling actively suppresses TNF mRNA levels by inducing expression of miR-21, resulting in decreased TNF mRNA stability. Conversely, EGFR inhibition results in loss of miR-21 and increased TNF mRNA stability. In addition, TNF-induced NF-κB activation leads to increased TNF transcription in a feed-forward loop. Inhibition of TNF signaling renders EGFRwt-expressing NSCLC cell lines and an EGFRwt patient-derived xenograft (PDX) model highly sensitive to EGFR inhibition. In EGFR-mutant oncogene-addicted cells, blocking TNF enhances the effectiveness of EGFR inhibition. EGFR plus TNF inhibition is also effective in NSCLC with acquired resistance to EGFR inhibition. We suggest concomitant EGFR and TNF inhibition as a potentially new treatment approach that could be beneficial for a majority of lung cancer patients.

  13. Periostin Limits Tumor Response to VEGFA Inhibition.

    Science.gov (United States)

    Keklikoglou, Ioanna; Kadioglu, Ece; Bissinger, Stefan; Langlois, Benoît; Bellotti, Axel; Orend, Gertraud; Ries, Carola H; De Palma, Michele

    2018-03-06

    Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA + stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2), an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R) antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. The neural markers of an imminent failure of response inhibition

    NARCIS (Netherlands)

    Bengson, Jesse J.; Mangun, George R.; Mazaheri, Ali

    2012-01-01

    In his novel Ulysses, James Joyce wrote that mistakes are the "...portals of discovery". The present study investigated the pre-stimulus oscillatory EEG signatures of selective attention and motor preparation that predicted failures of overt response inhibition. We employed a trial-by-trial spatial

  15. Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

    Directory of Open Access Journals (Sweden)

    Schmidt Martin H

    2008-01-01

    Full Text Available Abstract Background Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF profiles in children with ADHD and in children with ASD with and without comorbid ADHD. Methods Children aged 6 to 18 years old with ADHD (n = 20 or ASD (High-Functioning autism or Asperger syndrome with (n = 20 and without (n = 20 comorbid ADHD and a typically developing group (n = 20 were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used. Results There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02. Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01 and between the ADHD group, the ASD+ group (p = .03, the ASD- group (p = .02 and the TD group (p = .01 for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task. Conclusion Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for

  16. British Columbia inland oil spill response plan

    International Nuclear Information System (INIS)

    2005-01-01

    This paper presents an outline of the organization, procedures and duties of the provincial government in response to inland oil spills stemming from pipeline or tank-farm rupture, train derailment and vehicle accidents in British Columbia. Provincial response strategies were reviewed, along with their relationships to various policies and standards. Public, infrastructure and environmental protection were identified as key factors. Incident notification procedures were detailed, including outlines of roles, event criteria and call for incident management teams. Agreements and cost recovery issues were examined. The characteristics of site response were reviewed, including details of communications, tactical planning, and unified command among local and federal governments. The role of First Nations and responsible parties was also addressed. Details of shore cleanup, wildlife rescue, decontamination, and waste handling strategies were presented. The organization, missions and duties for an incident management team were outlined, along with a summary of operational guidelines and information on team positions and the establishment of joint information centres. The involvement of cooperating agencies was examined. An incident command system was also presented, including details of planning, operations, logistics, and organization. A checklist of individual duties was provided, with details of responsibilities, safety issues and general instructions for all team members. tabs., figs

  17. Response Inhibition Is Associated with White Matter Microstructure in Children

    Science.gov (United States)

    Madsen, Kathrine Skak; Baare, William F. C.; Vestergaard, Martin; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

    2010-01-01

    Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor…

  18. Response Inhibition and Cognitive Appraisal in Clients with Acute Stress Disorder and Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Abass Abolghasemi

    2013-09-01

    Full Text Available Objective: The purpose of the present study was to compare response inhibition and cognitive appraisal in clients with acute stress disorder, clients with posttraumatic stress disorder, and normal individuals .Method:This was a comparative study. The sample consisted of 40 clients with acute stress disorder, 40 patients with posttraumatic stress disorder, and 40 normal individuals from Mazandaran province selected through convenience sampling method. Data were collected using Composite International Diagnostic Interview, Stroop Color-Word Test, Posttraumatic Cognitions Inventory, and the Impact of Event Scale. Results:Results showed that individuals with acute stress disorder are less able to inhibit inappropriate responses and have more impaired cognitive appraisals compared to those with posttraumatic stress disorder. Moreover, results showed that response inhibition and cognitive appraisal explain 75% of the variance in posttraumatic stress disorder symptoms and 38% of the variance in posttraumatic stress disorder symptoms .Conclusion:The findings suggest that response inhibition and cognitive appraisal are two variables that influence the severity of posttraumatic stress disorder and acute stress disorder symptoms. Also, these results have important implications for pathology, prevention, and treatment of posttraumatic stress disorder and acute stress disorder

  19. Testing differential susceptibility: Plasticity genes, the social environment, and their interplay in adolescent response inhibition.

    Science.gov (United States)

    Richards, Jennifer S; Arias Vásquez, Alejandro; van Rooij, Daan; van der Meer, Dennis; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Hartman, Catharina A; Buitelaar, Jan K

    2017-06-01

    Impaired inhibitory control is a key feature of attention-deficit/hyperactivity disorder (ADHD). We investigated gene-environment interaction (GxE) as a possible contributing factor to response inhibition variation in context of the differential susceptibility theory. This states individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Behavioural and neural measures of response inhibition were assessed during a Stop-signal task in participants with (N = 197) and without (N = 295) ADHD, from N = 278 families (age M = 17.18, SD =3.65). We examined GxE between candidate plasticity genes (DAT1, 5-HTT, DRD4) and social environments (maternal expressed emotion, peer affiliation). A DRD4 × Positive peer affiliation interaction was found on the right fusiform gyrus (rFG) activation during successful inhibition. Further, 5-HTT short allele carriers showed increased rFG activation during failed inhibitions. Maternal warmth and positive peer affiliation were positively associated with right inferior frontal cortex activation during successful inhibition. Deviant peer affiliation was positively related to the error rate. While a pattern of differential genetic susceptibility was found, more clarity on the role of the FG during response inhibition is warranted before firm conclusions can be made. Positive and negative social environments were related to inhibitory control. This extends previous research emphasizing adverse environments.

  20. CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic Cell-Mediated CD4 T Cell Responses.

    Science.gov (United States)

    Wong, Kuan Y; Baron, Rebecca; Seldon, Therese A; Jones, Martina L; Rice, Alison M; Munster, David J

    2018-05-15

    Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells. Copyright © 2018 by The American Association of Immunologists, Inc.

  1. The development and revision of the Federal Radiological Emergency Response Plan

    International Nuclear Information System (INIS)

    Gant, K.S.; Adler, M.V.; Wolff, W.F.

    1989-01-01

    Since 1985, federal agencies have been using the Federal Radiological Emergency Response Plan (FRERP) in exercises and real events. This experience and the development of other emergency response guidance (e.g., National System for Emergency Coordination) are fueling current efforts to review and revise the FRERP to reflect what the agencies have learned since the FRERP was published. Revision efforts are concentrating on clarifying the plan and addressing deficiencies. No major changes are expected in the general structure of the federal response nor should states need to revise their plans because of these modifications. 5 refs

  2. Ethics and professional responsibility: Essential dimensions of planned home birth.

    Science.gov (United States)

    McCullough, Laurence B; Grünebaum, Amos; Arabin, Birgit; Brent, Robert L; Levene, Malcolm I; Chervenak, Frank A

    2016-06-01

    Planned home birth is a paradigmatic case study of the importance of ethics and professionalism in contemporary perinatology. In this article we provide a summary of recent analyses of the Centers for Disease Control database on attendants and birth outcomes in the United States. This summary documents the increased risks of neonatal mortality and morbidity of planned home birth as well as bias in Apgar scoring. We then describe the professional responsibility model of obstetric ethics, which is based on the professional medical ethics of two major figures in the history of medical ethics, Drs. John Gregory of Scotland and Thomas Percival of England. This model emphasizes the identification and careful balancing of the perinatologist's ethical obligations to pregnant, fetal, and neonatal patients. This model stands in sharp contrast to one-dimensional maternal-rights-based reductionist model of obstetric ethics, which is based solely on the pregnant woman's rights. We then identify the implications of the professional responsibility model for the perinatologist's role in directive counseling of women who express an interest in or ask about planned home birth. Perinatologists should explain the evidence of the increased, preventable perinatal risks of planned home birth, recommend against it, and recommend planned hospital birth. Perinatologists have the professional responsibility to create and sustain a strong culture of safety committed to a home-birth-like experience in the hospital. By routinely fulfilling these professional responsibilities perinatologists can help to prevent the documented, increased risks planned home birth. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 33 CFR Appendix C to Part 155 - Training Elements for Oil Spill Response Plans

    Science.gov (United States)

    2010-07-01

    .... 155, App. C Appendix C to Part 155—Training Elements for Oil Spill Response Plans 1. General 1.1The portion of the plan dealing with training is one of the key elements of a response plan. This concept is... included training as one of the sections required in a vessel or facility response plan. In reviewing...

  4. Emergency preparedness and response plan for nuclear facilities in Indonesia

    International Nuclear Information System (INIS)

    Nur Rahmah Hidayati; Pande Made Udiyani

    2009-01-01

    All nuclear facilities in Indonesia are owned and operated by the National Nuclear Energy Agency (BATAN). The programs and activities of emergency planning and preparedness in Indonesia are based on the existing nuclear facilities, i.e. research reactors, research reactor fuel fabrication plant, radioactive waste treatment installation and radioisotopes production installation. The assessment is conducted to learn of status of emergency preparedness and response plan for nuclear facilities in Indonesia and to support the preparation of future Nuclear Power Plant. The assessment is conducted by comparing the emergency preparedness and response system in Indonesia to the system in other countries such as Japan and Republic of Korea, since the countries have many Nuclear Power Plants and other nuclear facilities. As a result, emergency preparedness response plan for existing nuclear facility in Indonesia has been implemented in many activities such as environmental monitoring program, facility monitoring equipment, and the continuous exercise of emergency preparedness and response. However, the implementation need law enforcement for imposing the responsibility of the coordinators in National Emergency Preparedness Plan. It also needs some additional technical support systems which refer to the system in Japan or Republic of Korea. The systems must be completed with some real time monitors which will support the emergency preparedness and response organization. The system should be built in NPP site before the first NPP will be operated. The system should be connected to an Off Site Emergency Center under coordination of BAPETEN as the regulatory body which has responsibility to control of nuclear energy in Indonesia. (Author)

  5. Field assessment of a model tuberculosis outbreak response plan for low-incidence areas

    Directory of Open Access Journals (Sweden)

    Pascopella Lisa

    2007-10-01

    Full Text Available Abstract Background For a regional project in four low-incidence states, we designed a customizable tuberculosis outbreak response plan. Prior to dissemination of the plan, a tuberculosis outbreak occurred, presenting an opportunity to perform a field assessment of the plan. The purpose of the assessment was to ensure that the plan included essential elements to help public health professionals recognize and respond to outbreaks. Methods We designed a semi-structured questionnaire and interviewed all key stakeholders involved in the response. We used common themes to assess validity of and identify gaps in the plan. A subset of participants provided structured feedback on the plan. Results We interviewed 11 public health and six community stakeholders. The assessment demonstrated that (1 almost all of the main response activities were reflected in the plan; (2 the plan added value by providing a definition of a tuberculosis outbreak and guidelines for communication and evaluation. These were areas that lacked written protocols during the actual outbreak response; and (3 basic education about tuberculosis and the interpretation and use of genotyping data were important needs. Stakeholders also suggested adding to the plan questions for evaluation and a section for specific steps to take when an outbreak is suspected. Conclusion An interactive field assessment of a programmatic tool revealed the value of a systematic outbreak response plan with a standard definition of a tuberculosis outbreak, guidelines for communication and evaluation, and response steps. The assessment highlighted the importance of education and training for tuberculosis in low-incidence areas.

  6. Global phosphotyrosine proteomics identifies PKCδ as a marker of responsiveness to Src inhibition in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Eliot T McKinley

    Full Text Available Sensitive and specific biomarkers of protein kinase inhibition can be leveraged to accelerate drug development studies in oncology by associating early molecular responses with target inhibition. In this study, we utilized unbiased shotgun phosphotyrosine (pY proteomics to discover novel biomarkers of response to dasatinib, a small molecule Src-selective inhibitor, in preclinical models of colorectal cancer (CRC. We performed unbiased mass spectrometry shotgun pY proteomics to reveal the pY proteome of cultured HCT-116 colonic carcinoma cells, and then extended this analysis to HCT-116 xenograft tumors to identify pY biomarkers of dasatinib-responsiveness in vivo. Major dasatinib-responsive pY sites in xenograft tumors included sites on delta-type protein kinase C (PKCδ, CUB-domain-containing protein 1 (CDCP1, Type-II SH2-domain-containing inositol 5-phosphatase (SHIP2, and receptor protein-tyrosine phosphatase alpha (RPTPα. The pY313 site PKCδ was further supported as a relevant biomarker of dasatinib-mediated Src inhibition in HCT-116 xenografts by immunohistochemistry and immunoblotting with a phosphospecific antibody. Reduction of PKCδ pY313 was further correlated with dasatinib-mediated inhibition of Src and diminished growth as spheroids of a panel of human CRC cell lines. These studies reveal PKCδ pY313 as a promising readout of Src inhibition in CRC and potentially other solid tumors and may reflect responsiveness to dasatinib in a subset of colorectal cancers.

  7. Response Inhibition Function of Obsessive-Compulsive Patients with Obsessive-Compulsive Personality Disorder

    Directory of Open Access Journals (Sweden)

    Hui Lei

    2017-06-01

    Full Text Available Objective: To explore the effect of comorbid obsessive-compulsive personality disorder (OCPD on response inhibition functions in patients with obsessive-compulsive disorder (OCD. Methods: Forty-five obsessive-compulsive patients with obsessive-compulsive personality disorder (OCD + OCPD, 42 obsessive-compulsive patients without obsessive-compulsive personality disorder (OCD - OCPD and 54 healthy volunteers were selected for the stop-signal task. Results: Obsessive-compulsive patients with obsessive-compulsive personality disorder had a higher score of depression and anxiety and more severe obsessive-compulsive symptoms than that of obsessive-compulsive patients without obsessive-compulsive personality disorder. The two groups of obsessive-compulsive patients of had a greater stop-signal reaction time (SSRT during the inhibition process than the healthy volunteers of the control group (OCD + OCPD: 221.45 ± 31.78; OCD - OCPD: 218.36 ± 31.78; Controls: 199.29 ± 22.80; p < 0.05. However, no significant difference was found between the two groups of obsessive-compulsive patients. Conclusion: The findings show that the comorbid obsessive-compulsive personality disorder has no effect on response inhibition function of obsessive-compulsive patients.

  8. Guidance Manual for preparing Nuclear and Radiological Emergency Preparedness and Response Plan

    Energy Technology Data Exchange (ETDEWEB)

    Muhammed, Kabiru [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Jeong, Seung-Young [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-10-15

    The Nuclear and Radiological Emergency Preparedness and Response Plan(NREPRP) describes the capabilities, responsibilities and authorities of government agencies and a conceptual basis for integrating the activities of these agencies to protect public health and safety. The NREPRP addresses issues related to actual or perceived radiation hazard requiring a national response in order to: i. Provide co-ordination of a response involving multi-jurisdictions or significant national responsibilities; or ii. Provide national support to state and local governments. The objective of this research is to establish Guidance Manual for preparing a timely, organized and coordinated emergency response plan for Authorities/agencies to promptly and adequately determine and take actions to protect members of the public and emergency workers. The manual will not provide sufficient details for an adequate response. This level of details is contained in standard operating procedures that are being developed based on the plan developed. Base on the data obtain from integrated planning levels and responsibility sharing, the legal document of major government agencies participating in NREPRP form the legal basis for the response plan. Also the following documents should be some international legal binding documents. Base on the international safety requirement and some countries well developed NREPRP, we have drafted a guidance manual for new comer countries for easy development of their countries NREPRP. Also we have taken in to consideration lessons learn from most accident especially Fukushima accident.

  9. Guidance Manual for preparing Nuclear and Radiological Emergency Preparedness and Response Plan

    International Nuclear Information System (INIS)

    Muhammed, Kabiru; Jeong, Seung-Young

    2014-01-01

    The Nuclear and Radiological Emergency Preparedness and Response Plan(NREPRP) describes the capabilities, responsibilities and authorities of government agencies and a conceptual basis for integrating the activities of these agencies to protect public health and safety. The NREPRP addresses issues related to actual or perceived radiation hazard requiring a national response in order to: i. Provide co-ordination of a response involving multi-jurisdictions or significant national responsibilities; or ii. Provide national support to state and local governments. The objective of this research is to establish Guidance Manual for preparing a timely, organized and coordinated emergency response plan for Authorities/agencies to promptly and adequately determine and take actions to protect members of the public and emergency workers. The manual will not provide sufficient details for an adequate response. This level of details is contained in standard operating procedures that are being developed based on the plan developed. Base on the data obtain from integrated planning levels and responsibility sharing, the legal document of major government agencies participating in NREPRP form the legal basis for the response plan. Also the following documents should be some international legal binding documents. Base on the international safety requirement and some countries well developed NREPRP, we have drafted a guidance manual for new comer countries for easy development of their countries NREPRP. Also we have taken in to consideration lessons learn from most accident especially Fukushima accident

  10. Azadirachtin interacts with retinoic acid receptors and inhibits retinoic acid-mediated biological responses.

    Science.gov (United States)

    Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B; Sureshkumar, Chitta; Manna, Sunil K

    2011-02-11

    Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor κB (NF-κB) activation, not the DNA binding but the NF-κB-dependent gene expression. It did not inhibit IκBα degradation, IκBα kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-κB-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-κB activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-κB, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies.

  11. Azadirachtin Interacts with Retinoic Acid Receptors and Inhibits Retinoic Acid-mediated Biological Responses*

    Science.gov (United States)

    Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B.; Sureshkumar, Chitta; Manna, Sunil K.

    2011-01-01

    Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor κB (NF-κB) activation, not the DNA binding but the NF-κB-dependent gene expression. It did not inhibit IκBα degradation, IκBα kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-κB-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-κB activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-κB, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies. PMID:21127062

  12. Impaired Early-Response Inhibition in Overweight Females with and without Binge Eating Disorder.

    Directory of Open Access Journals (Sweden)

    Jennifer Svaldi

    Full Text Available Several studies report increased reward sensitivity towards food in overweight individuals. By contrast, data is inconclusive with respect to response inhibition in overweight individuals without binge eating disorder (BED. Hence, the latter was addressed in the present study in a group of overweight/obese females with and without BED and a normal-weight control group without eating disorders.A group of women with BED (n = 29, a group of overweight women without BED (n = 33 and normal-weight females (n = 30 participated in a pictorial priming paradigm, with food items (relevant primes and office utensils (neutral primes and color blobs (neutral primes as stimuli. Increased response priming effects (i.e. priming with switches between stimulus categories were taken as indicators of deficient behavioral inhibition.Priming effects for neutral primes were moderate and comparable across all groups. However, primes associated with the food task set lead to increased priming effects in both overweight groups. But, effects were comparable for overweight/obese participants with and without BED.Results suggest that early response inhibition in the context of food is impaired in overweight individuals compared to normal-weight individuals.

  13. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses.

    Science.gov (United States)

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J; Stunden, H James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R; Cain, Jason E; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

    2017-10-03

    Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40) large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development. IMPORTANCE Recent studies suggest that low-dose DNA-damaging compounds traditionally used in cancer therapy can have opposite effects on antiviral responses, either suppressing (with the example of CPT) or potentiating (with the example of doxorubicin) them. Our work demonstrates that the minor DNA damage promoted by low-dose CPT can also trigger strong antiviral responses, dependent on the presence of viral oncogenes. Taken together, these results call for caution in the therapeutic use of low-dose chemotherapy agents to modulate antiviral responses in humans. Copyright © 2017 Pépin et al.

  14. Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

    International Nuclear Information System (INIS)

    Khan, Shaheen; Liu Shengxi; Stoner, Matthew; Safe, Stephen

    2007-01-01

    The aryl hydrocarbon receptor (AhR) is expressed in estrogen receptor (ER)-positive ZR-75 breast cancer cells. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 protein and mRNA levels and also activates inhibitory AhR-ERα crosstalk associated with hormone-induced reporter gene expression. In ZR-75 cells grown under hypoxia, induction of these AhR-mediated responses by TCDD was significantly inhibited. This was not accompanied by decreased nuclear AhR levels or decreased interaction of the AhR complex with the CYP1A1 gene promoter as determined in a chromatin immunoprecipitation assay. Hypoxia-induced loss of Ah-responsiveness was not associated with induction of hypoxia-inducible factor-1α or other factors that sequester the AhR nuclear translocation (Arnt) protein, and overexpression of Arnt under hypoxia did not restore Ah-responsiveness. The p65 subunit of NFκB which inhibits AhR-mediated transactivation was not induced by hypoxia and was primarily cytosolic in ZR-75 cells grown under hypoxic and normoxic conditions. In ZR-75 cells maintained under hypoxic conditions for 24 h, BRCA1 (an enhancer of AhR-mediated transactivation in breast cancer cells) was significantly decreased and this contributed to loss of Ah-responsiveness. In cells grown under hypoxia for 6 h, BRCA1 was not decreased, but induction of CYP1A1 by TCDD was significantly decreased. Cotreatment of ZR-75 cells with TCDD plus the protein synthesis inhibitor cycloheximide for 6 h enhanced CYP1A1 expression in cells grown under hypoxia and normoxia. These results suggest that hypoxia rapidly induces protein(s) that inhibit Ah-responsiveness and these may be similar to constitutively expressed inhibitors of Ah-responsiveness (under normoxia) that are also inhibited by cycloheximide

  15. Using principles from emergency management to improve emergency response plans for research animals.

    Science.gov (United States)

    Vogelweid, Catherine M

    2013-10-01

    Animal research regulatory agencies have issued updated requirements for emergency response planning by regulated research institutions. A thorough emergency response plan is an essential component of an institution's animal care and use program, but developing an effective plan can be a daunting task. The author provides basic information drawn from the field of emergency management about best practices for developing emergency response plans. Planners should use the basic principles of emergency management to develop a common-sense approach to managing emergencies in their facilities.

  16. Dynamic sensorimotor planning during long-term sequence learning: the role of variability, response chunking and planning errors.

    Science.gov (United States)

    Verstynen, Timothy; Phillips, Jeff; Braun, Emily; Workman, Brett; Schunn, Christian; Schneider, Walter

    2012-01-01

    Many everyday skills are learned by binding otherwise independent actions into a unified sequence of responses across days or weeks of practice. Here we looked at how the dynamics of action planning and response binding change across such long timescales. Subjects (N = 23) were trained on a bimanual version of the serial reaction time task (32-item sequence) for two weeks (10 days total). Response times and accuracy both showed improvement with time, but appeared to be learned at different rates. Changes in response speed across training were associated with dynamic changes in response time variability, with faster learners expanding their variability during the early training days and then contracting response variability late in training. Using a novel measure of response chunking, we found that individual responses became temporally correlated across trials and asymptoted to set sizes of approximately 7 bound responses at the end of the first week of training. Finally, we used a state-space model of the response planning process to look at how predictive (i.e., response anticipation) and error-corrective (i.e., post-error slowing) processes correlated with learning rates for speed, accuracy and chunking. This analysis yielded non-monotonic association patterns between the state-space model parameters and learning rates, suggesting that different parts of the response planning process are relevant at different stages of long-term learning. These findings highlight the dynamic modulation of response speed, variability, accuracy and chunking as multiple movements become bound together into a larger set of responses during sequence learning.

  17. Electrophysiological indices of response inhibition in a Go/NoGo task predict self-control in a social context.

    Directory of Open Access Journals (Sweden)

    Kyle Nash

    Full Text Available Recent research demonstrates that response inhibition-a core executive function-may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test. Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes-two established electrophysiological indices of response inhibition-both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.

  18. Response inhibition is modulated by functional cerebral asymmetries for facial expression perception

    Directory of Open Access Journals (Sweden)

    Sebastian eOcklenburg

    2013-11-01

    Full Text Available The efficacy of executive functions is critically modulated by information processing in earlier cognitive stages. For example, initial processing of verbal stimuli in the language-dominant left-hemisphere leads to more efficient response inhibition than initial processing of verbal stimuli in the non-dominant right hemisphere. However, it is unclear whether this organizational principle is specific for the language system, or a general principle that also applies to other types of lateralized cognition. To answer this question, we investigated the neurophysiological correlates of early attentional processes, facial expression perception and response inhibition during tachistoscopic presentation of facial ‘Go’ and ‘Nogo’ stimuli in the left and the right visual field. Participants committed fewer false alarms after Nogo-stimulus presentation in the left compared to the right visual field. This right-hemispheric asymmetry on the behavioral level was also reflected in the neurophysiological correlates of face perception, specifically in a right-sided asymmetry in the N170 amplitude. Moreover, the right-hemispheric dominance for facial expression processing also affected event-related potentials typically related to response inhibition, namely the Nogo-N2 and Nogo-P3. These findings show that an effect of hemispheric asymmetries in early information processing on the efficacy of higher cognitive functions is not limited to left-hemispheric language functions, but can be generalized to predominantly right-hemispheric functions.

  19. Chronic Stress Impairs Prefrontal Cortex-Dependent Response Inhibition and Spatial Working Memory

    Science.gov (United States)

    Mika, Agnieszka; Mazur, Gabriel J.; Hoffman, Ann N.; Talboom, Joshua S.; Bimonte-Nelson, Heather A.; Sanabria, Federico; Conrad, Cheryl D.

    2012-01-01

    Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague Dawley rats were first trained on the RAWM and subsequently trained on FMI. Following acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when food reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing precision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher’s r to z transformation revealed no significant differences between control and stress with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task. PMID:22905921

  20. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    Science.gov (United States)

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-04-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

  1. Reduced short interval cortical inhibition correlates with atomoxetine response in children with attention-deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Chen, Tina H; Wu, Steve W; Welge, Jeffrey A; Dixon, Stephan G; Shahana, Nasrin; Huddleston, David A; Sarvis, Adam R; Sallee, Floyd R; Gilbert, Donald L

    2014-12-01

    Clinical trials in children with attention-deficit hyperactivity disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine. The objective of this study was to determine whether transcranial magnetic stimulation-evoked short interval cortical inhibition might be a biomarker predicting, or correlating with, clinical atomoxetine response. At baseline and after 4 weeks of atomoxetine treatment in 7- to 12-year-old children with ADHD, transcranial magnetic stimulation short interval cortical inhibition was measured, blinded to clinical improvement. Primary analysis was by multivariate analysis of covariance. Baseline short interval cortical inhibition did not predict clinical responses. However, paradoxically, after 4 weeks of atomoxetine, mean short interval cortical inhibition was reduced 31.9% in responders and increased 6.1% in nonresponders (analysis of covariance t 41 = 2.88; P = .0063). Percentage reductions in short interval cortical inhibition correlated with reductions in the ADHD Rating Scale (r = 0.50; P = .0005). In children ages 7 to 12 years with ADHD treated with atomoxetine, improvements in clinical symptoms are correlated with reductions in motor cortex short interval cortical inhibition. © The Author(s) 2014.

  2. Effects of a brief mindfulness-meditation intervention on neural measures of response inhibition in cigarette smokers.

    Directory of Open Access Journals (Sweden)

    Catherine I Andreu

    Full Text Available Research suggests that mindfulness-practices may aid smoking cessation. Yet, the neural mechanisms underlying the effects of mindfulness-practices on smoking are unclear. Response inhibition is a main deficit in addiction, is associated with relapse, and could therefore be a candidate target for mindfulness-based practices. The current study hence investigated the effects of a brief mindfulness-practice on response inhibition in smokers using behavioral and electroencephalography (EEG measures. Fifty participants (33 females, mean age 20 years old underwent a protocol of cigarette exposure to induce craving (cue-exposure and were then randomly assigned to a group receiving mindfulness-instructions or control-instructions (for 15 minutes approximately. Immediately after this, they performed a smoking Go/NoGo task, while their brain activity was recorded. At the behavioral level, no group differences were observed. However, EEG analyses revealed a decrease in P3 amplitude during NoGo vs. Go trials in the mindfulness versus control group. The lower P3 amplitude might indicate less-effortful response inhibition after the mindfulness-practice, and suggest that enhanced response inhibition underlies observed positive effects of mindfulness on smoking behavior.

  3. ANL site response for the DOE FY1994 information resources management long-range plan

    Energy Technology Data Exchange (ETDEWEB)

    Boxberger, L.M.

    1992-03-01

    Argonne National Laboratory's ANL Site Response for the DOE FY1994 Information Resources Management (IRM) Long-Range Plan (ANL/TM 500) is one of many contributions to the DOE information resources management long-range planning process and, as such, is an integral part of the DOE policy and program planning system. The Laboratory has constructed this response according to instructions in a Call issued in September 1991 by the DOE Office of IRM Policy, Plans and Oversight. As one of a continuing series, this Site Response is an update and extension of the Laboratory's previous submissions. The response contains both narrative and tabular material. It covers an eight-year period consisting of the base year (FY1991), the current year (FY1992), the budget year (FY1993), the plan year (FY1994), and the out years (FY1995-FY1998). This Site Response was compiled by Argonne National Laboratory's Computing and Telecommunications Division (CTD), which has the responsibility to provide leadership in optimizing computing and information services and disseminating computer-related technologies throughout the Laboratory. The Site Response consists of 5 parts: (1) a site overview, describes the ANL mission, overall organization structure, the strategic approach to meet information resource needs, the planning process, major issues and points of contact. (2) a software plan for DOE contractors, Part 2B, Software Plan FMS plan for DOE organizations, (3) computing resources telecommunications, (4) telecommunications, (5) printing and publishing.

  4. ANL site response for the DOE FY1994 information resources management long-range plan

    Energy Technology Data Exchange (ETDEWEB)

    Boxberger, L.M.

    1992-03-01

    Argonne National Laboratory`s ANL Site Response for the DOE FY1994 Information Resources Management (IRM) Long-Range Plan (ANL/TM 500) is one of many contributions to the DOE information resources management long-range planning process and, as such, is an integral part of the DOE policy and program planning system. The Laboratory has constructed this response according to instructions in a Call issued in September 1991 by the DOE Office of IRM Policy, Plans and Oversight. As one of a continuing series, this Site Response is an update and extension of the Laboratory`s previous submissions. The response contains both narrative and tabular material. It covers an eight-year period consisting of the base year (FY1991), the current year (FY1992), the budget year (FY1993), the plan year (FY1994), and the out years (FY1995-FY1998). This Site Response was compiled by Argonne National Laboratory`s Computing and Telecommunications Division (CTD), which has the responsibility to provide leadership in optimizing computing and information services and disseminating computer-related technologies throughout the Laboratory. The Site Response consists of 5 parts: (1) a site overview, describes the ANL mission, overall organization structure, the strategic approach to meet information resource needs, the planning process, major issues and points of contact. (2) a software plan for DOE contractors, Part 2B, ``Software Plan FMS plan for DOE organizations, (3) computing resources telecommunications, (4) telecommunications, (5) printing and publishing.

  5. 33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.

    Science.gov (United States)

    2010-07-01

    ... PREVENTION REGULATIONS FOR VESSELS Tank Vessel Response Plans for Oil § 155.1045 Response plan requirements... actions. (4) The organizational structure that will be used to manage the response actions. This structure... with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...

  6. 33 CFR Appendix D to Part 154 - Training Elements for Oil Spill Response Plans

    Science.gov (United States)

    2010-07-01

    ... Appendix D to Part 154—Training Elements for Oil Spill Response Plans 1. General 1.1The portion of the plan dealing with training is one of the key elements of a response plan. This concept is clearly expressed by... that the plans often do not provide sufficient information in the training section of the plan for...

  7. National response plan - Major nuclear or radiological accidents

    International Nuclear Information System (INIS)

    2014-02-01

    France has been implementing stringent radiation protection and nuclear safety and security measures for many years. However, this does not mean that the country is exempt from having to be prepared to deal with an emergency. Changes in France, Europe and other parts of the globe have made it necessary for France to reconsider how it responds to nuclear and radiological emergencies. As the potential impact of a nuclear or radiological accident can affect a wide range of activities, the plan described herein is based on a cross-sector and inter-ministerial approach to emergency response. The Chernobyl and Fukushima-Daiichi disasters are proof that the consequences of a major nuclear or radiological accident can affect all levels of society. These challenges are substantial and relate to: public health: An uncontrolled nuclear accident can have immediate consequences (death, injury, irradiation) as well as long-term consequences that can lead to increased risk of developing radiation-induced diseases (such as certain types of cancer); environmental quality: Radiation contamination can last for several decades and, in some cases, can result in an area being closed off permanently to the public; economic and social continuity: Nuclear accidents bring human activity to a halt in contaminated areas, disrupting the economic and social order of the entire country. It may therefore be necessary to adapt economic and social systems and carry out clean-up operations if people and businesses have been displaced; quality of international relations: Related to fulfillment of obligations to alert and inform European and international partners. This international dimension also covers the protection of French nationals present in countries stricken by a nuclear accident. This national plan provides reference information on how to prepare for a nuclear or radiological emergency and make the appropriate decisions in the event of an emergency. It covers the emergency phase (including

  8. Innovations in emergency response plans : making the useful application of the 2007 CDA guidelines for emergency response plans

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, A.J. [Columbia Power Corp., Castlegar, BC (Canada)

    2008-07-01

    Columbia Power Corporation (CPC) changed its perspective and approach to emergency response plans (ERP) between 2002 and 2007 from one of administrative necessity to one of important functional reference. The new 2007 Canadian Dam Association Guidelines helped facilitate that transition for both CPC and all dam owners. As part of the licensing requirements for its new facility, CPC had an ERP commissioned and developed in 2002. A potential dam safety event occurred in 2004, which necessitated the need for the ERP to be put to use. However, at the time, it was found to be lacking in functionality for field personnel. As a result, CPC recognized the significance of having a functional ERP for field staff and undertook a substantial redraft between 2005 and 2007. This paper discussed the development of the ERP with particular reference to assessing the top potential emergency scenarios for the facility; development of response plans for the identified scenarios; a flow chart to guide personnel through the required actions; response checklist; detailed inspection checklists and any required forms, photos or specific information. It was concluded that the new ERP has been well received and has improved facility awareness and emergency preparedness. 1 ref., 2 figs.

  9. Time orientation, planning horizons and responsibility into the future

    International Nuclear Information System (INIS)

    Svenson, O.; Nilsson, G.

    1988-01-01

    Subjects of four categories (social science students, engineering students, retired people and nuclear waste experts) were asked about past events, planning, risks and future time with emphasis on energy related issues and in particular questions concerning spent nuclear waste. Among, the results reported it was found that events in the past were located more or less correctly and that events further back systematically too close to the present. Today's responsibility into the future was judged to cover 3 to 6 generations ahead and an adequate planning horizon for a local community to be on the average 11 to 14 years. Adequate planning horizons for the handling of spent nuclear fuel were judged to be from 100 to 500 years. The responsibility for effects of today's decisions was judged to be from about 100 to 300 years into the future for environmental pollution and from about 50 to 600 years for nuclear waste. However, non-negliqable proportions of the subjects choose a more moral standpoint and gave answers indicating that responsibility had to be unlimited. Some sex differences were found and an interaction with age offered as a hypothesis to be investigated in the future. Interrelations between clusters of questions revealed some links from past time and planning to judgements of environmental and nuclear power related risks. (orig.)

  10. Oak Ridge National Laboratory Corrective Action Plan in response to Tiger Team assessment

    International Nuclear Information System (INIS)

    1991-01-01

    This report presents a complete response to the Tiger Team assessment that was conducted to Oak Ridge National Laboratory (ORNL) and at the US Department of Energy (DOE) Oak Ridge Operations Office (ORO) from October 2, 1990, through November 30, 1990. The action plans have undergone both a discipline review and a cross-cutting review with respect to root cause. In addition, the action plans have been integrated with initiatives being pursued across Martin Marietta Energy Systems, Inc., in response to Tiger Team findings at other DOE facilities operated by Energy Systems. The root cause section is complete and describes how ORNL intends to address the root cause of the findings identified during the assessment. This report is concerned with reactors safety and health findings, responses, and planned actions. Specific areas include: organization and administration; quality verification; operations; maintenance; training and certification; auxiliary systems; emergency preparedness; technical support; nuclear criticality safety; security/safety interface; experimental activities; site/facility safety review; radiological protection; personnel protection; fire protection; management findings, responses, and planned actions; self-assessment findings, responses, and planned actions; and summary of planned actions, schedules, and costs

  11. Emergency response planning for transport accidents involving radioactive materials

    International Nuclear Information System (INIS)

    1982-03-01

    The document presents a basic discussion of the various aspects and philosophies of emergency planning and preparedness along with a consideration of the problems which might be encountered in a transportation accident involving a release of radioactive materials. Readers who are responsible for preparing emergency plans and procedures will have to decide on how best to apply this guidance to their own organizational structures and will also have to decide on an emergency planning and preparedness philosophy suitable to their own situations

  12. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  13. Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

    Science.gov (United States)

    Gaval-Cruz, Meriem; Liles, Larry Cameron; Iuvone, Paul Michael; Weinshenker, David

    2012-01-01

    The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh −/−) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/−) and Dbh −/− mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh −/− mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/− mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/− mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh −/− mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors. PMID:23209785

  14. A cross-sectional analysis of the development of response inhibition in children with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Heather M Shapiro

    2013-08-01

    Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is a neurogenetic disorder that is associated with cognitive impairments and significantly elevated risk for developing schizophrenia. While impairments in response inhibition are central to executive dysfunction in schizophrenia, the nature and development of such impairments in children with 22q11.2DS, a group at high risk for the disorder, are not clear. Here we used a classic Go/No-Go paradigm to quantify proactive (anticipatory stopping and reactive (actual stopping response inhibition in 47 children with 22q11.2DS and 36 typically developing (TD children, all ages 7-14. A cross-sectional design was used to examine age-related associations with response inhibition. When compared with TD individuals, children with 22q11.2DS demonstrated typical proactive response inhibition at all ages. By contrast, reactive response inhibition was impaired in children with 22q11.2DS relative to TD children. While older age predicted better reactive response inhibition in TD children, there was no age-related association with reactive response inhibition in children with 22q11.2DS. Closer examination of individual performance data revealed a wide range of performance abilities in older children with 22q11.2DS; some typical and others highly impaired. The results of this cross-sectional analysis suggest an impaired developmental trajectory of reactive response inhibition in some children with 22q11.2DS that might be related to atypical development of neuroanatomical systems underlying this cognitive process. As part of a larger study, this investigation might help identify risk factors for conversion to schizophrenia and lead to early diagnosis and preventive intervention.

  15. Stopping at the sight of food - How gender and obesity impact on response inhibition.

    Science.gov (United States)

    Mühlberg, Christoph; Mathar, David; Villringer, Arno; Horstmann, Annette; Neumann, Jane

    2016-12-01

    Recent research indicates that reduced inhibitory control is associated with higher body mass index (BMI), higher food craving and increased food intake. However, experimental evidence for the relationship between response inhibition and weight status is inconsistent and to date has been investigated predominantly in women. In the current study, 56 participants (26 obese, 30 lean; 27 female, 29 male) performed a Food Picture Rating Task followed by a Stop Signal Task where pictures of palatable high or low caloric food or non-food items were presented prior to the Go signal. We further assessed participants' self-reported eating behavior and trait impulsivity as potential factors influencing response inhibition, in particular within the food context. Independent of BMI, women showed significantly higher liking for low caloric food items than men. This was accompanied by shorter Stop Signal Reaction Times (SSRT) after high compared to low caloric food pictures for women, and shorter SSRT in women compared to men for high caloric food. No influence of gender on SSRT was observable outside of the food context. While SSRTs did not differ between obese and lean participants across the three picture categories, we found a moderating effect of trait impulsivity on the relationship between BMI and SSRT, specifically in the high caloric food context. Higher BMI was predictive of longer SSRT only for participants with low to normal trait impulsivity, pointing at a complex interplay between response inhibition, general impulsivity and weight status. Our results support the notion that individuals with obesity do not suffer from diminished response inhibition capacity per se. Rather, the ability to withhold a response depends on context and social norms, and strongly interacts with factors like gender and trait impulsivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 30 CFR 254.7 - How do I submit my response plan to the MMS?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I submit my response plan to the MMS... do I submit my response plan to the MMS? You must submit the number of copies of your response plan that the appropriate MMS regional office requires. If you prefer to use improved information technology...

  17. Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Tibu, F; Sheridan, M A; McLaughlin, K A; Nelson, C A; Fox, N A; Zeanah, C H

    2016-02-01

    Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.

  18. 45 CFR 673.5 - Emergency response plan.

    Science.gov (United States)

    2010-10-01

    ... ensure that: (a) The vessel owner's or operator's shipboard oil pollution emergency plan, prepared and... Pollution from Ships, 1973, as modified by the Protocol of 1978 relating thereto (MARPOL 73/78), has provisions for prompt and effective response action to such emergencies as might arise in the performance of...

  19. Public comments and responses to the 1991 Hanford Cleanup Five-Year Plan

    International Nuclear Information System (INIS)

    1992-05-01

    The Department of Energy (DOE) Richland Field Office (RL) updated its Site-Specific Plan (DOE-RL 1991a) dealing with cleanup and operation of the Hanford Site in September 1991. The plan provides direction as to how DOE will carry out the national strategy for managing and cleaning up the Hanford Site wastes resulting from production of nuclear weapons. The plan is updated annually. We asked the public to comment on the plan during its 60-day public comment period. This report presents the comments and provides responses. The introduction explains how the comments were gathered and how we responded. This report is in four main sections: (1) comments and responses addressed locally; (2) comments forwarded to DOE-Headquarters for their response (these responses will appear in the National Five-Year Plan [DOE 1991a]); (3) comments we did not respond to here because they were outside the scope, or about how we gathered the public's comments; and (4) the appendices, which include a glossary, a list of acronyms used in the document, and the letters and cards we received reproduced in their entirety

  20. Event-related fields evoked by vocal response inhibition: a comparison of younger and older adults.

    Science.gov (United States)

    Castro-Meneses, Leidy J; Johnson, Blake W; Sowman, Paul F

    2016-06-01

    The current study examined event-related fields (ERFs) evoked by vocal response inhibition in a stimulus-selective stop-signal task. We compared inhibition-related ERFs across a younger and an older group of adults. Behavioural results revealed that stop-signal reaction times (RTs), go-RTs, ignore-stop RTs and failed stop RTs were longer in the older, relative to the younger group by 38, 123, 149 and 116 ms, respectively. The amplitude of the ERF M2 peak (approximately 200 ms after the stop signal) evoked on successful stop trials was larger compared to that evoked on both failed stop and ignore-stop trials. The M4 peak (approximately 450 ms after stop signal) was of larger amplitude in both successful and failed stops compared to ignore-stop trials. In the older group, the M2, M3 and M4 peaks were smaller in amplitude and peaked later in time (by 24, 50 and 76 ms, respectively). We demonstrate that vocal response inhibition-related ERFs exhibit a similar temporal evolution to those previously described for manual response inhibition: an early peak at 200 ms (i.e. M2) that differentiates successful from failed stopping, and a later peak (i.e. M4) that is consistent with a neural marker of response checking and error processing. Across groups, our data support a more general decline of stimulus processing speed with age.

  1. Intergenerational Transmission of Risk for Social Inhibition: the Interplay between Parental Responsiveness and Genetic Influences

    Science.gov (United States)

    Natsuaki, Misaki N.; Leve, Leslie D.; Neiderhiser, Jenae M.; Shaw, Daniel S.; Scaramella, Laura V.; Ge, Xiaojia; Reiss, David

    2013-01-01

    To better understand mechanisms underlying the intergenerational transmission of social anxiety, we used a prospective adoption design to examine the roles of genetic influences (inferred from birth mothers’ social phobia) and rearing environment (adoptive mothers’ and fathers’ responsiveness) on the development of socially inhibited, anxious behaviors in children between 18 and 27 months of age. The sample consisted of 275 adoption-linked families, each including an adopted child, adoptive parents, and a birth mother. Results indicated that children whose birth mothers met criteria for the diagnosis of social phobia showed elevated levels of observed behavioral inhibition in a social situation at 27 months of age if their adoptive mothers provided less emotionally and verbally responsive rearing environments at 18 months of age. Conversely, in the context of higher levels of maternal responsiveness, children of birth mothers with a history of social phobia did not show elevated levels of behavioral inhibition. These findings on maternal responsiveness were replicated in a model predicting parent reports of child social anxiety. The findings are discussed in terms of genotype × environment interactions in the intergenerational transmission of social anxiety. PMID:23398764

  2. Intergenerational transmission of risk for social inhibition: the interplay between parental responsiveness and genetic influences.

    Science.gov (United States)

    Natsuaki, Misaki N; Leve, Leslie D; Neiderhiser, Jenae M; Shaw, Daniel S; Scaramella, Laura V; Ge, Xiaojia; Reiss, David

    2013-02-01

    To better understand mechanisms underlying the intergenerational transmission of social anxiety, we used a prospective adoption design to examine the roles of genetic influences (inferred from birth mothers' social phobia) and rearing environment (adoptive mothers' and fathers' responsiveness) on the development of socially inhibited, anxious behaviors in children between 18 and 27 months of age. The sample consisted of 275 adoption-linked families, each including an adopted child, adoptive parents, and a birth mother. Results indicated that children whose birth mothers met criteria for the diagnosis of social phobia showed elevated levels of observed behavioral inhibition in a social situation at 27 months of age if their adoptive mothers provided less emotionally and verbally responsive rearing environments at 18 months of age. Conversely, in the context of higher levels of maternal responsiveness, children of birth mothers with a history of social phobia did not show elevated levels of behavioral inhibition. These findings on maternal responsiveness were replicated in a model predicting parent reports of child social anxiety. The findings are discussed in terms of gene-environment interactions in the intergenerational transmission of social anxiety.

  3. Nuclear emergency planning and response in the Netherlands after Chernobyl

    International Nuclear Information System (INIS)

    Bergman, L.J.W.M.; Kerkhoven, I.P.

    1989-01-01

    After Chernobyl an extensive project on nuclear emergency planning and response was started in the Netherlands. The objective of this project was to develop a (governmental) structure to cope with accidents with radioactive materials, that can threaten the Dutch community and neighbouring countries. The project has resulted in a new organizational structure for nuclear emergency response, that differs on major points from the existing plans and procedures. In this paper an outline of the new structure is given. Emphasis is placed on accidents with nuclear power plants

  4. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    International Nuclear Information System (INIS)

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina

    2013-01-01

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca ++ influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  5. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro-Filho, Jaime [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Moraes de Carvalho, Katharinne Ingrid [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Mendes, Diego da [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Melo, Christianne Bandeira [Laboratório de Inflamação, Instituto Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro (Brazil); Martins, Marco Aurélio [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Dias, Celidarque da [Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba (Brazil); Piuvezam, Márcia Regina, E-mail: mrpiuvezam@ltf.ufpb.br [Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  6. IFN-γ fails to overcome inhibition of selected macrophage activation events in response to pathogenic mycobacteria.

    Directory of Open Access Journals (Sweden)

    Shyamala Thirunavukkarasu

    Full Text Available According to most models of mycobacterial infection, inhibition of the pro-inflammatory macrophage immune responses contributes to the persistence of bacteria. Mycobacterium avium subsp. paratuberculosis (MAP is a highly successful pathogen in cattle and sheep and is also implicated as the causative agent of Crohn's disease in humans. Pathogenic mycobacteria such as MAP have developed multiple strategies to evade host defence mechanisms including interfering with the macrophages' capacity to respond to IFN-γ, a feature which might be lacking in non-pathogenic mycobacteria such as M. smegmatis. We hypothesized that pre-sensitisation of macrophages with the pro-inflammatory cytokine IFN-γ would help in overcoming the inhibitory effect of MAP or its antigens on macrophage inflammatory responses. Herein we have compared a series of macrophage activation parameters in response to MAP and M. smegmatis as well as mycobacterial antigens. While IFN-γ did overcome the inhibition in immune suppressive mechanisms in response to MAP antigen as well as M. smegmatis, we could not find a clear role for IFN-γ in overcoming the inhibition of macrophage inflammatory responses to the pathogenic mycobacterium, MAP. We demonstrate that suppression of macrophage defence mechanisms by pathogenic mycobacteria is unlikely to be overcome by prior sensitization with IFN-γ alone. This indicates that IFN-γ signaling pathway-independent mechanisms may exist for overcoming inhibition of macrophage effector functions in response to pathogenic mycobacteria. These findings have important implications in understanding the survival mechanisms of pathogenic mycobacteria directed towards finding better therapeutics and vaccination strategies.

  7. Inhibition of the mitotic exit network in response to damaged telomeres.

    Directory of Open Access Journals (Sweden)

    Mauricio Valerio-Santiago

    Full Text Available When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN, in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression.

  8. Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine.

    Science.gov (United States)

    Nagarajah, James; Le, Mina; Knauf, Jeffrey A; Ferrandino, Giuseppe; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Saqcena, Mahesh; Larson, Steven M; Ho, Alan L; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A; Fagin, James A

    2016-11-01

    Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer.

  9. Attention Diversion Improves Response Inhibition of Immediate Reward, But Only When it Is Beneficial: An fMRI Study

    Science.gov (United States)

    Scalzo, Franco; O’Connor, David A.; Orr, Catherine; Murphy, Kevin; Hester, Robert

    2016-01-01

    Deficits of self-control are associated with a number of mental state disorders. The ability to direct attention away from an alluring stimulus appears to aid inhibition of an impulsive response. However, further functional imaging research is required to assess the impact of shifts in attention on self-regulating processes. We varied the level of attentional disengagement in an functional magnetic resonance imaging (fMRI)-based Go/No-go task to probe whether diversion of attention away from alluring stimuli facilitates response inhibition. We used the attention-grabbing characteristic of faces to exogenously direct attention away from stimuli and investigated the relative importance of attention and response inhibition mechanisms under different delayed reward scenarios [i.e., where forgoing an immediate reward ($1) led to a higher ($10) or no payoff in the future]. We found that diverting attention improved response inhibition performance, but only when resistance to an alluring stimulus led to delayed reward. Region of interest analyses indicated significant increased activity in posterior right inferior frontal gyrus during successful No-go trials for delayed reward trials compared to no delayed reward trials, and significant reduction in activity in the superior temporal gyri and left caudate in contexts of high attentional diversion. Our findings imply that strategies that increase the perceived benefits of response inhibition might assist individuals in abstaining from problematic impulsive behaviors. PMID:27616988

  10. Prestimulus neural oscillations inhibit visual perception via modulation of response gain.

    Science.gov (United States)

    Chaumon, Maximilien; Busch, Niko A

    2014-11-01

    The ongoing state of the brain radically affects how it processes sensory information. How does this ongoing brain activity interact with the processing of external stimuli? Spontaneous oscillations in the alpha range are thought to inhibit sensory processing, but little is known about the psychophysical mechanisms of this inhibition. We recorded ongoing brain activity with EEG while human observers performed a visual detection task with stimuli of different contrast intensities. To move beyond qualitative description, we formally compared psychometric functions obtained under different levels of ongoing alpha power and evaluated the inhibitory effect of ongoing alpha oscillations in terms of contrast or response gain models. This procedure opens the way to understanding the actual functional mechanisms by which ongoing brain activity affects visual performance. We found that strong prestimulus occipital alpha oscillations-but not more anterior mu oscillations-reduce performance most strongly for stimuli of the highest intensities tested. This inhibitory effect is best explained by a divisive reduction of response gain. Ongoing occipital alpha oscillations thus reflect changes in the visual system's input/output transformation that are independent of the sensory input to the system. They selectively scale the system's response, rather than change its sensitivity to sensory information.

  11. Response inhibition moderates the association between drug use and risky sexual behavior.

    Science.gov (United States)

    Nydegger, Liesl A; Ames, Susan L; Stacy, Alan W; Grenard, Jerry L

    2014-09-01

    HIV infection is problematic among all drug users, not only injection drug users. Drug users are at risk for contracting HIV by engaging in risky sexual behaviors. The present study sought to determine whether inhibitory processes moderate the relationship between problematic drug use and HIV-risk behaviors (unprotected sex and multiple sex partners). One hundred ninety-six drug offenders enrolled in drug education programs were administered a battery of computer-based assessments. Measures included a cued go/no-go assessment of inhibitory processes, the Drug Abuse Screening Test (DAST) assessment of problematic drug use, and self-report assessment of condom use and multiple sex partners. Findings revealed that response inhibition assessed by the proportion of false alarms on the cued go/no-go moderated the relationship between problematic drug use and an important measure of HIV risk (condom nonuse) among drug offenders. However, response inhibition did not moderate the relationship between problematic drug use and another measure of HIV risk: multiple sex partners. Among this sample of drug offenders, we have found a relationship between problematic drug use and condom nonuse, which is exacerbated by poor control of inhibition. These findings have implications for the development of HIV intervention components among high-risk populations.

  12. A synthetic peptide blocking TRPV1 activation inhibits UV-induced skin responses.

    Science.gov (United States)

    Kang, So Min; Han, Sangbum; Oh, Jang-Hee; Lee, Young Mee; Park, Chi-Hyun; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2017-10-01

    Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues. We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin. We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr 705 , and tested its efficacy of blocking UV-induced responses in HaCaT, mouse, and human skin. TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV-induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo. The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  13. Response Inhibition during Cue Reactivity in Problem Gamblers: An fMRI Study

    NARCIS (Netherlands)

    van Holst, Ruth J.; van Holstein, Mieke; van den Brink, Wim; Veltman, Dick J.; Goudriaan, Anna E.

    2012-01-01

    Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition

  14. Planning for off-site response to radiation accidents in nuclear facilities

    International Nuclear Information System (INIS)

    1981-01-01

    The purpose of this publication is to give guidance to those who are responsible for the protection of the public in the event of an accident occurring at a land-based nuclear facility. This guidance should assist in the advance preparation of emergency response plans and implementing procedures. Basic principles of protective measures along with their advantages and disadvantages are discussed. Other principles related to emergency planning and the operational response to an emergency are outlined. Although the guidance is primarily oriented towards land-based nuclear power facilities, the guidance does have general application to other types of nuclear facility

  15. Planning for off-site response to radiation accidents in nuclear facilities

    International Nuclear Information System (INIS)

    1979-01-01

    The purpose of this manual is to give guidance to those who are responsible for the protection of the public in the event of an accident occurring at a land-based nuclear facility. This guidance should assist in the advance preparation of emergency response plans and implementing procedures. Basic principles of protective measures along with their advantages and disadvantages are discussed. Other principles related to emergency planning and the operational response to an emergency are outlined. Although the guidance is primarily oriented toward land-based nuclear power facilities, the guidance does have general application to other types of nuclear facilities

  16. Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response.

    Science.gov (United States)

    Hempstead, Andrew D; Isberg, Ralph R

    2015-12-08

    Cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. One system that responds to these stimuli is the IRE1 branch of the unfolded protein response (UPR), a sensor of endoplasmic reticulum (ER) stress. Activation of IRE1, in the context of Toll-like receptor (TLR) signaling, induces strong proinflammatory cytokine induction. We show here that Legionella pneumophila, an intravacuolar pathogen that replicates in an ER-associated compartment, blocks activation of the IRE1 pathway despite presenting pathogen products that stimulate this response. L. pneumophila TLR ligands induced the splicing of mRNA encoding XBP1s, the main target of IRE1 activity. L. pneumophila was able to inhibit both chemical and bacterial induction of XBP1 splicing via bacterial translocated proteins that interfere with host protein translation. A strain lacking five translocated translation elongation inhibitors was unable to block XBP1 splicing, but this could be rescued by expression of a single such inhibitor, consistent with limitation of the response by translation elongation inhibitors. Chemical inhibition of translation elongation blocked pattern recognition receptor-mediated XBP1 splicing, mimicking the effects of the bacterial translation inhibitors. In contrast, host cell-promoted inhibition of translation initiation in response to the pathogen was ineffective in blocking XBP1 splicing, demonstrating the need for the elongation inhibitors for protection from the UPR. The inhibition of host translation elongation may be a common strategy used by pathogens to limit the innate immune response by interfering with signaling via the UPR.

  17. An emergency response plan for transportation

    International Nuclear Information System (INIS)

    Fontaine, M.V.; Guerel, E.

    2000-01-01

    Transnucleaire is involved in road and rail transport of nuclear fuel cycle materials. To comply with IAEA recommendations, Transnucleaire has to master methods of emergency response in the event of a transport accident. Considering the utmost severe situations, Transnucleaire has studied several cases and focused especially on an accident involving a heavy cask. In France, the sub-prefect of each department is in charge of the organisation of the emergency teams. The sub-prefect may request Transnucleaire to supply experts, organisation, equipment and technical support. The Transnucleaire Emergency Response Plan covers all possible scenarios of land transport accidents and relies on: (i) an organisation ready for emergency situations, (ii) equipment dedicated to intervention, and (iii) training of its own experts and specialised companies. (author)

  18. The management of acute risks. Oil spill contingency planning and response

    International Nuclear Information System (INIS)

    Monk, D.C.; Cormack, D.

    1992-01-01

    It is clear that the risks of environmental damage can be best minimized by preventing oil spills from occurring at all. Since absolute prevention is unrealistic, however, early detection is essential and aerial surveillance techniques are of great value in this connection. If spills do occur, proper contingency planning and clean-up techniques can minimize impacts, but will rarely avoid them completely if the spilled oil reaches the coastline. It is evident that a main priority should be to prevent spilled oil reaching the coastline. The way in which oil spill response strategy is implemented is discussed in detail. It is based on four key elements: the allocation of responsibilities; contingency planning; training and exercises; regular audit of plans and response mechanisms. A case study of the oil spill strategy employed at the Sullom Voe oil terminal in Shetland is used as an illustration. (UK)

  19. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

    Science.gov (United States)

    Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

    2014-01-01

    Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

  20. Planning and Preparing for Emergency Response to Transport Accidents Involving Radioactive Material. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide provides guidance on various aspects of emergency planning and preparedness for dealing effectively and safely with transport accidents involving radioactive material, including the assignment of responsibilities. It reflects the requirements specified in Safety Standards Series No. TS-R-1, Regulations for the Safe Transport of Radioactive Material, and those of Safety Series No. 115, International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources. Contents: 1. Introduction; 2. Framework for planning and preparing for response to accidents in the transport of radioactive material; 3. Responsibilities for planning and preparing for response to accidents in the transport of radioactive material; 4. Planning for response to accidents in the transport of radioactive material; 5. Preparing for response to accidents in the transport of radioactive material; Appendix I: Features of the transport regulations influencing emergency response to transport accidents; Appendix II: Preliminary emergency response reference matrix; Appendix III: Guide to suitable instrumentation; Appendix IV: Overview of emergency management for a transport accident involving radioactive material; Appendix V: Examples of response to transport accidents; Appendix VI: Example equipment kit for a radiation protection team; Annex I: Example of guidance on emergency response to carriers; Annex II: Emergency response guide.

  1. Response Inhibition and ADHD Traits: Correlates and Heritability in a Community Sample

    Science.gov (United States)

    Crosbie, J.; Arnold, P.; Paterson, A.; Swanson, J.; Dupuis, A.; Li, X.; Shan, J.; Goodale, T.; Tam, C.; Strug, L. J.; Schachar, R. J.

    2013-01-01

    Endophenotypes or intermediate phenotypes are of great interest in neuropsychiatric genetics because of their potential for facilitating gene discovery. We evaluated response inhibition, latency and variability measures derived from the stop task as endophenotypes of ADHD by testing whether they were related to ADHD traits in the general…

  2. Modulation of radiation response by histone deacetylase inhibition

    International Nuclear Information System (INIS)

    Chinnaiyan, Prakash; Vallabhaneni, Geetha; Armstrong, Eric M.S.; Huang, Shyh-Min; Harari, Paul M.

    2005-01-01

    Purpose: Histone deacetylase (HDAC) inhibitors, which modulate chromatin structure and gene expression, represent a class of anticancer agents that hold particular potential as radiation sensitizers. In this study, we examine the capacity of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) to modulate radiation response in human tumor cell lines and explore potential mechanisms underlying these interactions. Methods and materials: Cell proliferation: Exponentially growing tumor cells were incubated in medium containing 0-10 μM of SAHA for 72 h. Cells were fixed/stained with crystal violet to estimate cell viability. Apoptosis: Caspase activity was analyzed by fluorescence spectroscopy using a fluorescein labeled pan-caspase inhibitor. Cells were harvested after 48 h of exposure to SAHA (1.0 μM), radiation (6 Gy), or the combination. Whole cell lysates were evaluated for poly(ADP-ribose) polymerase (PARP) cleavage by western blot analysis. Radiation survival: Cells were exposed to varying doses of radiation ± 3 days pretreatment with SAHA (0.75-1.0 μM). After incubation intervals of 14-21 days, colonies were stained with crystal violet and manually counted. Immunocytochemistry: Cells were grown and treated in chamber slides. At specified times after treatment with SAHA, cells were fixed in paraformaldehyde, permeabilized in methanol, and probed with primary and secondary antibody solutions. Slides were analyzed using an epifluorescent microscope. Results: SAHA induced a dose-dependent inhibition of proliferation in human prostate (DU145) and glioma (U373vIII) cancer cell lines. Exposure to SAHA enhanced radiation-induced apoptosis as measured by caspase activity (p < 0.05) and PARP cleavage. The impact of SAHA on radiation response was further characterized using clonogenic survival analysis, which demonstrated that treatment with SAHA reduced tumor survival after radiation exposure. We identified several oncoproteins and DNA damage repair proteins

  3. Detecting and Responding to a Dengue Outbreak: Evaluation of Existing Strategies in Country Outbreak Response Planning

    Directory of Open Access Journals (Sweden)

    Julia Harrington

    2013-01-01

    Full Text Available Background. Dengue outbreaks are occurring with increasing frequency and intensity. Evidence-based epidemic preparedness and effective response are now a matter of urgency. Therefore, we have analysed national and municipal dengue outbreak response plans. Methods. Thirteen country plans from Asia, Latin America and Australia, and one international plan were obtained from the World Health Organization. The information was transferred to a data analysis matrix where information was extracted according to predefined and emerging themes and analysed for scope, inconsistencies, omissions, and usefulness. Findings. Outbreak response planning currently has a considerable number of flaws. Outbreak governance was weak with a lack of clarity of stakeholder roles. Late timing of responses due to poor surveillance, a lack of combining routine data with additional alerts, and lack of triggers for initiating the response weakened the functionality of plans. Frequently an outbreak was not defined, and early response mechanisms based on alert signals were neglected. There was a distinct lack of consideration of contextual influences which can affect how an outbreak detection and response is managed. Conclusion. A model contingency plan for dengue outbreak prediction, detection, and response may help national disease control authorities to develop their own more detailed and functional context specific plans.

  4. Prefrontal activity during response inhibition decreases over time in the postpartum period.

    Science.gov (United States)

    Bannbers, Elin; Gingnell, Malin; Engman, Jonas; Morell, Arvid; Sylvén, Sara; Skalkidou, Alkistis; Kask, Kristiina; Bäckström, Torbjörn; Wikström, Johan; Poromaa, Inger Sundström

    2013-03-15

    The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. A bi-level integrated generation-transmission planning model incorporating the impacts of demand response by operation simulation

    International Nuclear Information System (INIS)

    Zhang, Ning; Hu, Zhaoguang; Springer, Cecilia; Li, Yanning; Shen, Bo

    2016-01-01

    Highlights: • We put forward a novel bi-level integrated power system planning model. • Generation expansion planning and transmission expansion planning are combined. • The effects of two sorts of demand response in reducing peak load are considered. • Operation simulation is conducted to reflect the actual effects of demand response. • The interactions between the two levels can guarantee a reasonably optimal result. - Abstract: If all the resources in power supply side, transmission part, and power demand side are considered together, the optimal expansion scheme from the perspective of the whole system can be achieved. In this paper, generation expansion planning and transmission expansion planning are combined into one model. Moreover, the effects of demand response in reducing peak load are taken into account in the planning model, which can cut back the generation expansion capacity and transmission expansion capacity. Existing approaches to considering demand response for planning tend to overestimate the impacts of demand response on peak load reduction. These approaches usually focus on power reduction at the moment of peak load without considering the situations in which load demand at another moment may unexpectedly become the new peak load due to demand response. These situations are analyzed in this paper. Accordingly, a novel approach to incorporating demand response in a planning model is proposed. A modified unit commitment model with demand response is utilized. The planning model is thereby a bi-level model with interactions between generation-transmission expansion planning and operation simulation to reflect the actual effects of demand response and find the reasonably optimal planning result.

  6. Characteristics of Effective Collaboration in Response to Diversified Transportation Planning Authority

    OpenAIRE

    John S. Miller

    2011-01-01

    Advantages of decentralized transportation planning responsibilities may include reduced project delivery cost, the integration of comprehensive long-range planning with regional land use, and greater accountability regarding local concerns. Yet disadvantages may include a tendency for operations to dominate longer-term planning, inconsistent operational standards, and difficulty in achieving network benefits, since some transportation links may provide benefits to the entire system but not ...

  7. Emergency planning, response and assessment: a concept for a center of excellence

    International Nuclear Information System (INIS)

    Dickerson, M.H.

    1986-01-01

    This paper discusses a general concept for a center of excellence devoted to emergency planning, response and assessment. A plan is presented to implement the concept, based on experience gained from emergency response as it relates to the nuclear and toxic chemical industries. The role of the World Laboratory in this endeavor would complement and enhance other organizations than are involved in related activities

  8. Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: some preliminary evidence from event-related potentials

    Directory of Open Access Journals (Sweden)

    Petit G

    2014-06-01

    Full Text Available Géraldine Petit, Agnieszka Cimochowska, Charles Kornreich, Catherine Hanak, Paul Verbanck, Salvatore CampanellaLaboratory of Psychological Medicine and Addictology, ULB Neuroscience Institute (UNI, Université Libre de Bruxelles (ULB, Brussels, BelgiumBackground: Alcohol dependence is a chronic relapsing disease. The impairment of response inhibition and alcohol-cue reactivity are the main cognitive mechanisms that trigger relapse. Despite the interaction suggested between the two processes, they have long been investigated as two different lines of research. The present study aimed to investigate the interaction between response inhibition and alcohol-cue reactivity and their potential link with relapse.Materials and methods: Event-related potentials were recorded during a variant of a “go/no-go” task. Frequent and rare stimuli (to be inhibited were superimposed on neutral, nonalcohol-related, and alcohol-related contexts. The task was administered following a 3-week detoxification course. Relapse outcome was measured after 3 months, using self-reported abstinence. There were 27 controls (seven females and 27 patients (seven females, among whom 13 relapsed during the 3-month follow-up period. The no-go N2, no-go P3, and the “difference” wave (P3d were examined with the aim of linking neural correlates of response inhibition on alcohol-related contexts to the observed relapse rate.Results: Results showed that 1 at the behavioral level, alcohol-dependent patients made significantly more commission errors than controls (P<0.001, independently of context; 2 through the subtraction no-go P3 minus go P3, this inhibition deficit was neurophysiologically indexed in patients with greater P3d amplitudes (P=0.034; and 3 within the patient group, increased P3d amplitude enabled us to differentiate between future relapsers and nonrelapsers (P=0.026.Conclusion: Our findings suggest that recently detoxified alcoholics are characterized by poorer

  9. Development of quantitative methods for spill response planning: a trajectory analysis planner

    International Nuclear Information System (INIS)

    Galt, J.A.; Payton, D.L.

    1999-01-01

    In planning for response to oil spills, a great deal of information must be assimilated. Typically, geophysical flow patterns, ocean turbulence, complex chemical processes, ecological setting, fisheries activities, economics of land use, and engineering constraints on response equipment all need to be considered. This presents a formidable analysis problem. It can be shown, however, that if an appropriate set of evaluation data is available, an objective function and appropriate constraints can be formulated. From these equations, the response problem can be cast in terms of game theory of decision analysis and an optimal solution can be obtained using common scarce-resource allocation methods. The optimal solution obtained by this procedure maximises the expected return over all possible implementations of a given set of response options. While considering the development of an optimal spill response, it is useful to consider whether (in the absence of complete data) implementing some subset of these methods is possible to provide relevant and useful information for the spill planning process, even though it may fall short of a statistically optimal solution. In this work we introduce a trajectory analysis planning (TAP) methodology that can provide a cohesive framework for integrating physical transport processes, environmental sensitivity of regional sites, and potential response options. This trajectory analysis planning methodology can be shown to implement a significant part of the game theory analysis and provide 'minimum regret' strategy advice, without actually carrying out the optimisation procedures. (Author)

  10. Development of emergency response plans for community water ...

    African Journals Online (AJOL)

    All water services systems, irrespective of size, location etc., should have emergency response plans (ERPs) to guide officials, stakeholders and consumers through emergencies, as part of managing risks in the water supply system. Emergencies in the water supply system may result from, among other causes, natural ...

  11. Influence of Response Prepotency Strength, General Working Memory Resources, and Specific Working Memory Load on the Ability to Inhibit Predominant Responses: A Comparison of Young and Elderly Participants

    Science.gov (United States)

    Grandjean, Julien; Collette, Fabienne

    2011-01-01

    One conception of inhibitory functioning suggests that the ability to successfully inhibit a predominant response depends mainly on the strength of that response, the general functioning of working memory processes, and the working memory demand of the task (Roberts, Hager, & Heron, 1994). The proposal that inhibition and functional working memory…

  12. Response Requirement and Nature of Interpolated Stories in Retroactive Inhibition in Prose.

    Science.gov (United States)

    Van Mondfrans, Adrian P.; And Others

    Retroactive inhibition, a loss of memory due to learning other materials between recall and exposure to the original materials, was investigated in relation to prose. Two variables were manipulated in the study: similarity of interpolated stories (dissimilar or similar), and the response requirements (completion-recall or multiple-choice). The 190…

  13. Technology disaster response and recovery planning a LITA guide

    CERN Document Server

    Mallery, Mary

    2015-01-01

    Featuring contributions from librarians who offer hard-won advice gained from personal experience, this compendium leads readers through a step-by-step process of creating a library technology disaster response and recovery plan.

  14. A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.

    Science.gov (United States)

    Aquea, Felipe; Federici, Fernan; Moscoso, Cristian; Vega, Andrea; Jullian, Pastor; Haseloff, Jim; Arce-Johnson, Patricio

    2012-04-01

    Boron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We show that application of BA reduces the size of root meristems, correlating with the inhibition of root growth. The decrease in meristem size is caused by a reduction of cell division. Mitotic cell number significantly decreases and the expression level of key core cell cycle regulators is modulated. The modulation of the cell cycle does not appear to act through cytokinin and auxin signalling. A global expression analysis reveals that boron toxicity induces the expression of genes related with abscisic acid (ABA) signalling, ABA response and cell wall modifications, and represses genes that code for water transporters. These results suggest that boron toxicity produces a reduction of water and BA uptake, triggering a hydric stress response that produces root growth inhibition. © 2011 Blackwell Publishing Ltd.

  15. Computer Security Incident Response Planning at Nuclear Facilities

    International Nuclear Information System (INIS)

    2016-06-01

    The purpose of this publication is to assist Member States in developing comprehensive contingency plans for computer security incidents with the potential to impact nuclear security and/or nuclear safety. It provides an outline and recommendations for establishing a computer security incident response capability as part of a computer security programme, and considers the roles and responsibilities of the system owner, operator, competent authority, and national technical authority in responding to a computer security incident with possible nuclear security repercussions

  16. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yijun [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Lu, Hongjuan [Productivity Center of Jiangsu Province, Nanjing 210042, Jiangsu (China); Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Taylor, Ethan Will [Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC 27402 (United States); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

    2012-12-15

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  17. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    International Nuclear Information System (INIS)

    Wang, Yijun; Lu, Hongjuan; Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun; Taylor, Ethan Will; Zhang, Jinsong

    2012-01-01

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  18. Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.

    Science.gov (United States)

    Quartulli, F; Pinelli, E; Broué-Chabbert, A; Gossart, S; Girard, V; Pipy, B

    1998-05-08

    Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.

  19. Mood and restrained eating moderate food-associated response inhibition in obese individuals with binge eating disorder.

    Science.gov (United States)

    Loeber, Sabine; Rustemeier, Martina; Paslakis, Georgios; Pietrowsky, Reinhard; Müller, Astrid; Herpertz, Stephan

    2018-03-30

    Recent research suggests that obese individuals with binge eating disorder (BED) show deficits in response inhibition, but findings are not consistent, especially when food-associated stimuli are presented. The aim of the present study was to assess the role of moderating factors by taking into account restrained eating and mood. Seventeen obese women with BED, 20 obese women without BED and 20 normal-weight controls (NW) were recruited. A go/no-go task with food-associated and control stimuli and questionnaires were administered. Obese BED showed less impairment of response inhibition to food-associated than to control stimuli, while this pattern was reversed in NW; no differences were observed for obese participants. Interestingly, group differences were moderated by the interaction of restrained eating and mood, and obese BED made the most commission errors to food-associated stimuli when they were restrained eaters and in a very positive mood at the time of testing. Our results might explain why some studies did not observe deficits in response inhibition to food-associated cues in BED. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Paradox effects of binge drinking on response inhibition processes depending on mental workload.

    Science.gov (United States)

    Stock, Ann-Kathrin; Riegler, Lea; Chmielewski, Witold X; Beste, Christian

    2016-06-01

    Binge drinking is an increasing problem in Western societies, but we are still only beginning to unravel the effects of binge drinking on a cognitive level. While common sense suggests that all cognitive functions are compromised during high-dose ethanol intoxication, several studies suggest that the effects might instead be rather specific. Moreover, some results suggest that the degrees of automaticity and complexity of cognitive operations during response control modulate effects of binge drinking. However, this has not been tested in detail. In the current study, we therefore parametrically modulate cognitive/"mental" workload during response inhibition and examine the effects of high-dose ethanol intoxication (~1.1 ‰) in n = 18 male participants. The results suggest that detrimental effects of high-dose ethanol intoxication strongly depend on the complexity of processes involved in response inhibition. The results revealed strong effects (η (2) = .495) and are in line with findings showing that even high doses of ethanol have very specific effects on a cognitive level. Opposed to common sense, more complex cognitive operations seem to be less affected by a high-dose ethanol intoxication. Complementing this, high-dose ethanol intoxication is increasingly detrimental for action control, as stronger automated response tendencies are in charge and need to be controlled. Binge-like ethanol intoxication may take a heavier toll on cognitive control processes than on automated responses/response tendencies. Therefore, ethanol effects are more pronounced in supposedly "easier" control conditions because those facilitate the formation of automated response tendencies.

  1. Poverty and internalizing symptoms: The indirect effect of middle childhood poverty on internalizing symptoms via an emotional response inhibition pathway

    Directory of Open Access Journals (Sweden)

    Christian G. Capistrano

    2016-08-01

    Full Text Available Childhood poverty is a pervasive problem that can alter mental health outcomes. Children from impoverished circumstances are more likely than their middle-income counterparts to develop internalizing problems such as depression and anxiety. To date, however, the emotional-cognitive control processes that link childhood poverty and internalizing symptoms remain largely unexplored. Using the Emotion Go/NoGo paradigm, we examined the association between poverty and emotional response inhibition in middle childhood. We further examined the role of emotional response inhibition in the link between middle childhood poverty and internalizing symptoms. Lower income was associated with emotional response inhibition difficulties (indexed by greater false alarm rates in the context of task irrelevant angry and sad faces. Furthermore, emotional response inhibition deficits in the context of angry and sad distracters were further associated with child-report internalizing problems. The results of the current study demonstrate the significance of understanding the emotional-cognitive control vulnerabilities of children raised in poverty and their association with mental health outcomes.

  2. Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

    Science.gov (United States)

    Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

    2015-04-01

    Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  3. TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms.

    Directory of Open Access Journals (Sweden)

    Sarah A Benson

    2009-07-01

    Full Text Available Mycobacterium tuberculosis uses multiple mechanisms to avoid elimination by the immune system. We have previously shown that M. tuberculosis can inhibit selected macrophage responses to IFN-gamma through TLR2-dependent and -independent mechanisms. To specifically address the role of TLR2 signaling in mediating this inhibition, we stimulated macrophages with the specific TLR2/1 ligand Pam(3CSK(4 and assayed responses to IFN-gamma. Pam(3CSK(4 stimulation prior to IFN-gamma inhibited transcription of the unrelated IFN-gamma-inducible genes, CIITA and CXCL11. Surface expression of MHC class II and secretion of CXCL11 were greatly reduced as well, indicating that the reduction in transcripts had downstream effects. Inhibition of both genes required new protein synthesis. Using chromatin immunoprecipitation, we found that TLR2 stimulation inhibited IFN-gamma-induced RNA polymerase II binding to the CIITA and CXCL11 promoters. Furthermore, TATA binding protein was unable to bind the TATA box of the CXCL11 promoter, suggesting that assembly of transcriptional machinery was disrupted. However, TLR2 stimulation affected chromatin modifications differently at each of the inhibited promoters. Histone H3 and H4 acetylation was reduced at the CIITA promoter but unaffected at the CXCL11 promoter. In addition, NF-kappaB signaling was required for inhibition of CXCL11 transcription, but not for inhibition of CIITA. Taken together, these results indicate that TLR2-dependent inhibition of IFN-gamma-induced gene expression is mediated by distinct, gene-specific mechanisms that disrupt binding of the transcriptional machinery to the promoters.

  4. A comparative study of ethylene growth response kinetics in eudicots and monocots reveals a role for gibberellin in growth inhibition and recovery.

    Science.gov (United States)

    Kim, Joonyup; Wilson, Rebecca L; Case, J Brett; Binder, Brad M

    2012-11-01

    Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa 'Nipponbare') seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics.

  5. Deficits in Response Inhibition in Patients with Attention-Deficit/Hyperactivity Disorder: The Impaired Self-Protection System Hypothesis

    Directory of Open Access Journals (Sweden)

    Thales Vianna Coutinho

    2018-01-01

    Full Text Available Problems in inhibitory control are regarded in Psychology as a key problem associated with attention-deficit/hyperactivity disorder (ADHD. They, however, might not be primary deficits, but instead a consequence of inattention. At least two components have been identified and dissociated in studies in regards to inhibitory control: interference suppression, responsible for controlling interference by resisting irrelevant or misleading information, and response inhibition, referring to withholding a response or overriding an ongoing behavior. Poor error awareness and self-monitoring undermine an individual’s ability to inhibit inadequate responses and change course of action. In non-social contexts, an individual depends on his own cognition to regulate his mistakes. In social contexts, however, there are many social cues that should help that individual to perceive his mistakes and inhibit inadequate responses. The processes involved in perceiving and interpreting those social cues are arguably part of a self-protection system (SPS. Individuals with ADHD not only present impulsive behaviors in social contexts, but also have difficulty perceiving their inadequate responses and overriding ongoing actions toward more appropriate ones. In this paper, we discuss that those difficulties are arguably a consequence of an impaired SPS, due to visual attention deficits and subsequent failure in perceiving and recognizing accurately negative emotions in facial expressions, especially anger. We discuss evidence that children with ADHD exhibit problems in a series of components involved in the activation of that system and advocate that the inability to identify the anger expressed by others, and thus, not experiencing the fear response that should follow, is, ultimately, what prevents them from inhibiting the ongoing inappropriate behavior, since a potential threat is not registered. Getting involved in high-risk situations, such as reckless driving, could

  6. Response inhibition deficits in externalizing child psychiatric disorders: An ERP-study with the Stop-task

    Directory of Open Access Journals (Sweden)

    Heinrich Hartmut

    2005-12-01

    Full Text Available Abstract Background Evidence from behavioural studies suggests that impaired motor response inhibition may be common to several externalizing child psychiatric disorders, although it has been proposed to be the core-deficit in AD/HD. Since similar overt behaviour may be accompanied by different covert brain activity, the aim of this study was to investigate both brain-electric-activity and performance measures in three groups of children with externalizing child psychiatric disorders and a group of normal controls. Methods A Stop-task was used to measure specific aspects of response inhibition in 10 children with attention-deficit hyperactivity disorder (AD/HD, 8 children with oppositional defiant disorder/conduct disorder (ODD/CD, 11 children with comorbid AD/HD+ODD/CD and 11 normal controls. All children were between 8 and 14 years old. Event-related potentials and behavioural responses were recorded. An initial go-signal related microstate, a subsequent Stop-signal related N200, and performance measures were analyzed using ANCOVA with age as covariate. Results Groups did not differ in accuracy or reaction time to the Go-stimuli. However, all clinical groups displayed reduced map strength in a microstate related to initial processing of the Go-stimulus compared to normal controls, whereas topography did not differ. Concerning motor response inhibition, the AD/HD-only and the ODD/CD-only groups displayed slower Stop-signal reaction times (SSRT and Stop-failure reaction time compared to normal controls. In children with comorbid AD/HD+ODD/CD, Stop-failure reaction-time was longer than in controls, but their SSRT was not slowed. Moreover, SSRT in AD/HD+ODD/CD was faster than in AD/HD-only or ODD/CD-only. The AD/HD-only and ODD/CD-only groups displayed reduced Stop-N200 mean amplitude over right-frontal electrodes. This effect reached only a trend for comorbid AD/HD+ODD/CD. Conclusion Following similar attenuations in initial processing of the Go

  7. Differential Effects of Social and Non-Social Reward on Response Inhibition in Children and Adolescents

    Science.gov (United States)

    Kohls, Gregor; Peltzer, Judith; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2009-01-01

    An important issue in the field of clinical and developmental psychopathology is whether cognitive control processes, such as response inhibition, can be specifically enhanced by motivation. To determine whether non-social (i.e. monetary) and social (i.e. positive facial expressions) rewards are able to differentially improve response inhibition…

  8. Developing a highway emergency response plan for incidents involving hazardous materials, second edition, March 1992

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This provides minimum guidelines for developing an emergency response plan for incidents involving hazardous liquid hydrocarbons, such as gasoline and crude oil, transported in MC 306/DOT 406 and MC 307/DOT 407 aluminum cargo tanks and for coordinating and cooperating with local, state, and federal officials. This publication covers response plan priorities, personnel training, special equipment, media relations, environmental relations, and post-response activities. The apprendixes to this recommended practice outline a highway emergency response plan and suggest a procedure for removing liquid hydrocarbons from overturned cargo tanks and righting the tank vehicles

  9. Variation in serotonin neurotransmission genes affects neural activation during response inhibition in adolescents and young adults with ADHD and healthy controls

    NARCIS (Netherlands)

    Van Rooij, Daan; Hartman, Catharina A.; Van Donkelaar, Marjolein M. J.; Bralten, Janita; Von Rhein, Daniel; Hakobjan, Marina; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Rommelse, Nanda; Buitelaar, Jan K.; Hoekstra, Pieter J.

    2015-01-01

    Objectives. Deficits in response inhibition have been associated with attention-deficit/hyperactivity disorder (ADHD). Given the role of serotonin in ADHD and impulsivity, we postulated that genetic variants within the serotonin pathway might influence response inhibition. Methods. We measured

  10. Environmental emergency response plans (EERPs): A single plan approach to satisfy multiple regulations

    International Nuclear Information System (INIS)

    Muzyka, L.

    1995-01-01

    Conrail is a freight railroad operating in twelve northeast and midwestern states transporting goods and materials over 11,700 miles of railroad. To repair, maintain, rebuild, and manufacture locomotives and rail cars, and to maintain the track, right of way, bridges, tunnels and other structures, Conrail uses petroleum products, solvents and cleaners. These products are stored in hundreds of storage tanks in and around the yards and right of way. To power the trains, locomotives are fueled with diesel fuel. With large volumes of fuel, lubricants, solvents and cleaners, safe and efficient handling of petroleum and chemicals is crucial to avoid negative impacts on the environment. Conrail recently revisited the issue of environmental emergency response planning. In an attempt to assure full compliance with a myriad of federal, state, and local regulation, a ''single plan approach'' was chosen. Single plans for each facility, coined EERPs, were decided on after careful review of the regulations, and evaluation of the company's operational and organizational needs

  11. E3 Ligase cIAP2 Mediates Downregulation of MRE11 and Radiosensitization in Response to HDAC Inhibition in Bladder Cancer.

    Science.gov (United States)

    Nicholson, Judith; Jevons, Sarah J; Groselj, Blaz; Ellermann, Sophie; Konietzny, Rebecca; Kerr, Martin; Kessler, Benedikt M; Kiltie, Anne E

    2017-06-01

    The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is posttranslational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated. Truncated MRE11 was stabilized by proteasome inhibition, exhibited a decreased half-life after treatment with panobinostat, and therefore represents a newly identified intermediate induced and degraded in response to HDAC inhibition. The E3 ligase cellular inhibitor of apoptosis protein 2 (cIAP2) was upregulated in response to HDAC inhibition and was validated as a new MRE11 binding partner whose upregulation had similar effects to HDAC inhibition. cIAP2 overexpression resulted in downregulation and altered ubiquitination patterns of MRE11 and mediated radiosensitization in response to HDAC inhibition. These results highlight cIAP2 as a player in the DNA damage response as a posttranscriptional regulator of MRE11 and identify cIAP2 as a potential target for biomarker discovery or chemoradiation strategies in bladder cancer. Cancer Res; 77(11); 3027-39. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Avoidance behaviour response and esterase inhibition in the earthworm, Lumbricus terrestris, after exposure to chlorpyrifos.

    Science.gov (United States)

    Martínez Morcillo, S; Yela, J L; Capowiez, Y; Mazzia, C; Rault, M; Sanchez-Hernandez, Juan C

    2013-05-01

    The avoidance response of earthworms to polluted soils has been standardised using a simple and low-cost test, which facilitates soil toxicity screening. In this study, the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos-spiked soils, depending on the pesticide concentration and exposure duration. The inhibition of acetylcholinesterase (AChE) and carboxylesterase (CbE) activities was also determined as indirect measures of pesticide bioavailability. The effects of different chlorpyrifos concentrations were examined in a standardised test (two-chamber system) with 0.6, 3 and 15 mg/kg chlorpyrifos. A modification of the test involved a pre-exposure step (24, 48 or 72 h) in soils spiked with 15 mg/kg. In both protocols, earthworms were unable to avoid the contaminated soils. However, the esterase activities showed that all earthworms were exposed to chlorpyrifos. Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test (0.58 ± 0.20 U/mg protein, mean ± SD; n = 72), whereas the CbE activity was significantly inhibited (62-87 % inhibition) in earthworms exposed to 3 and 15 mg/kg. In the modified test, earthworms had greatly inhibited AChE activity (0.088 ± 0.034 U/mg protein, n = 72), which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime (2-PAM). Similarly, the CbE activity was significantly inhibited in earthworms with all treatments. This study suggests that the avoidance behaviour test for organophosphorus-contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test.

  13. Dietary flavonoid derivatives enhance chemotherapeutic effect by inhibiting the DNA damage response pathway

    International Nuclear Information System (INIS)

    Kuo, Ching-Ying; Zupkó, István; Chang, Fang-Rong; Hunyadi, Attila; Wu, Chin-Chung; Weng, Teng-Song; Wang, Hui-Chun

    2016-01-01

    Flavonoids are the most common group of polyphenolic compounds and abundant in dietary fruits and vegetables. Diet high in vegetables or dietary flavonoid supplements is associated with reduced mortality rate for patients with breast cancer. Many studies have been proposed for mechanisms linking flavonoids to improving chemotherapy efficacy in many types of cancers, but data on this issue is still limited. Herein, we report on a new mechanism through which dietary flavonoids inhibit DNA damage checkpoints and repair pathways. We found that dietary flavonoids could inhibit Chk1 phosphorylation and decrease clonogenic cell growth once breast cancer cells receive ultraviolet irradiation, cisplatin, or etoposide treatment. Since the ATR-Chk1 pathway mainly involves response to DNA replication stress, we propose that flavonoid derivatives reduce the side effect of chemotherapy by improving the sensitivity of cycling cells. Therefore, we propose that increasing intake of common dietary flavonoids is beneficial to breast cancer patients who are receiving DNA-damaging chemotherapy, such as cisplatin or etoposide-based therapy. - Highlights: • First report on inhibition of both DNA damage and repair by dietary flavonoids • Dietary flavonoids inhibit cisplatin- and UV-induced Chk1 phosphorylation. • Flavonoids combined with cisplatin or UV treatment show notable growth inhibition. • Promising treatment proposal for patients who are receiving adjuvant chemotherapy

  14. Dietary flavonoid derivatives enhance chemotherapeutic effect by inhibiting the DNA damage response pathway

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Ching-Ying [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Zupkó, István [Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös Utca 6, Szeged H-6720 (Hungary); Chang, Fang-Rong [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hunyadi, Attila [Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Eötvös Utca 6, Szeged H-6720 (Hungary); Wu, Chin-Chung; Weng, Teng-Song [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Wang, Hui-Chun, E-mail: wanghc@kmu.edu.tw [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); PhD Program in Translational Medicine, College of Medicine and PhD Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Research Center for Natural Product and Drug Development, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Translational Research Center and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan (China); Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan (China); Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2016-11-15

    Flavonoids are the most common group of polyphenolic compounds and abundant in dietary fruits and vegetables. Diet high in vegetables or dietary flavonoid supplements is associated with reduced mortality rate for patients with breast cancer. Many studies have been proposed for mechanisms linking flavonoids to improving chemotherapy efficacy in many types of cancers, but data on this issue is still limited. Herein, we report on a new mechanism through which dietary flavonoids inhibit DNA damage checkpoints and repair pathways. We found that dietary flavonoids could inhibit Chk1 phosphorylation and decrease clonogenic cell growth once breast cancer cells receive ultraviolet irradiation, cisplatin, or etoposide treatment. Since the ATR-Chk1 pathway mainly involves response to DNA replication stress, we propose that flavonoid derivatives reduce the side effect of chemotherapy by improving the sensitivity of cycling cells. Therefore, we propose that increasing intake of common dietary flavonoids is beneficial to breast cancer patients who are receiving DNA-damaging chemotherapy, such as cisplatin or etoposide-based therapy. - Highlights: • First report on inhibition of both DNA damage and repair by dietary flavonoids • Dietary flavonoids inhibit cisplatin- and UV-induced Chk1 phosphorylation. • Flavonoids combined with cisplatin or UV treatment show notable growth inhibition. • Promising treatment proposal for patients who are receiving adjuvant chemotherapy.

  15. Management response plan for the Chemical Safety Vulnerability Working Group report. Volume 2

    International Nuclear Information System (INIS)

    1994-09-01

    The Chemical Safety Vulnerability (CSV) Working Group was established to identify adverse conditions involving hazardous chemicals at DOE facilities that might result in fires or explosions, release of hazardous chemicals to the environment, or exposure of workers or the public to chemicals. A CSV Review was conducted in 146 facilities at 29 sites. Eight generic vulnerabilities were documented related to: abandoned chemicals and chemical residuals; past chemical spills and ground releases; characterization of legacy chemicals and wastes; disposition of legacy chemicals; storage facilities and conditions; condition of facilities and support systems; unanalyzed and unaddressed hazards; and inventory control and tracking. Weaknesses in five programmatic areas were also identified related to: management commitment and planning; chemical safety management programs; aging facilities that continue to operate; nonoperating facilities awaiting deactivation; and resource allocations. To address the facility-specific and site-specific vulnerabilities, responsible DOE and site-contractor line organizations have developed initial site response plans. These plans, presented as Volume 2 of this Management Response Plan, describe the actions needed to mitigate or eliminate the facility- and site-specific vulnerabilities identified by the CSV Working Group field verification teams. Initial site response plans are described for: Brookhaven National Lab., Hanford Site, Idaho National Engineering Lab., Lawrence Livermore National Lab., Los Alamos National Lab., Oak Ridge Reservation, Rocky Flats Plant, Sandia National Laboratories, and Savannah River Site

  16. Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells.

    Directory of Open Access Journals (Sweden)

    Thomas Heiberg

    2016-05-01

    Full Text Available Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs and interneurons (INs form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so-called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non-linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive-field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition and regulation of spatial

  17. Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells.

    Science.gov (United States)

    Heiberg, Thomas; Hagen, Espen; Halnes, Geir; Einevoll, Gaute T

    2016-05-01

    Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN) in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs) and interneurons (INs) form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC) input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so-called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non-linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive-field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition) and regulation of spatial resolution

  18. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    Energy Technology Data Exchange (ETDEWEB)

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  19. Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review.

    Science.gov (United States)

    Zilverstand, Anna; Huang, Anna S; Alia-Klein, Nelly; Goldstein, Rita Z

    2018-06-06

    The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Planning and implementing nuclear emergency response facilities

    International Nuclear Information System (INIS)

    Williams, D.H.

    1983-01-01

    After Three Mile Island, Arkansas Nuclear One produced a planning document called TMI-2 Response Program. Phase I of the program defined action plans in nine areas: safety assessment, training, organization, public information, communication, security, fiscal-governmental, technical and logistical support. Under safety assessment, the staff was made even better prepared to handle radioactive material. Under training, on site simulators for each unit at ANO were installed. The other seven topics interface closely with each other. An emergency control center is diagrammed. A habitable technical support system was created. A media center, with a large media area, and an auditorium, was built. Electric door strike systems increased security. Phone networks independently run via microwave were installed. Until Three Mile Island, logistical problems were guesswork. That incident afforded an opportunity to better identify and prepare for these problems

  1. New Structure of Emergency Response Plan in Croatia

    International Nuclear Information System (INIS)

    Valcic, I.; Subasic, D.; Cavlina, N.

    1998-01-01

    The new structure of a national emergency response plan in the case of nuclear accident is based on general requirements of modernization according to international recommendations, with a new Technical Support Center as a so-called lead technical agency, with the plan adapted to the organization of the Civil Protection, with all necessary elements of preparedness for the event of a nuclear accident in Krsko NPP and Paks NPP and with such a plan of procedures that will, to greatest possible extent, be compatible with the existing plan in neighboring countries Slovenia and Hungary. The main requirement that direct s a new organization scheme for taking protective actions in the event of a nuclear accident, is the requirement of introducing a Technical Support Center. The basic role of TSC is collecting data and information on nuclear accident, analyzing and estimating development of an accident, and preparing proposals for taking protective actions and for informing the public. TSC is required to forward those proposals to the Civil Protection, which on the basis of evaluation of proposals makes decisions on implementation and surveillance of implementation of protective measures. (author)

  2. The BUMP model of response planning: intermittent predictive control accounts for 10 Hz physiological tremor.

    Science.gov (United States)

    Bye, Robin T; Neilson, Peter D

    2010-10-01

    Physiological tremor during movement is characterized by ∼10 Hz oscillation observed both in the electromyogram activity and in the velocity profile. We propose that this particular rhythm occurs as the direct consequence of a movement response planning system that acts as an intermittent predictive controller operating at discrete intervals of ∼100 ms. The BUMP model of response planning describes such a system. It forms the kernel of Adaptive Model Theory which defines, in computational terms, a basic unit of motor production or BUMP. Each BUMP consists of three processes: (1) analyzing sensory information, (2) planning a desired optimal response, and (3) execution of that response. These processes operate in parallel across successive sequential BUMPs. The response planning process requires a discrete-time interval in which to generate a minimum acceleration trajectory to connect the actual response with the predicted future state of the target and compensate for executional error. We have shown previously that a response planning time of 100 ms accounts for the intermittency observed experimentally in visual tracking studies and for the psychological refractory period observed in double stimulation reaction time studies. We have also shown that simulations of aimed movement, using this same planning interval, reproduce experimentally observed speed-accuracy tradeoffs and movement velocity profiles. Here we show, by means of a simulation study of constant velocity tracking movements, that employing a 100 ms planning interval closely reproduces the measurement discontinuities and power spectra of electromyograms, joint-angles, and angular velocities of physiological tremor reported experimentally. We conclude that intermittent predictive control through sequential operation of BUMPs is a fundamental mechanism of 10 Hz physiological tremor in movement. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Should we stop thinking about inhibition? Searching for individual and age differences in inhibition ability.

    Science.gov (United States)

    Rey-Mermet, Alodie; Gade, Miriam; Oberauer, Klaus

    2018-04-01

    Inhibition is often conceptualized as a unitary construct reflecting the ability to ignore and suppress irrelevant information. At the same time, it has been subdivided into inhibition of prepotent responses (i.e., the ability to stop dominant responses) and resistance to distracter interference (i.e., the ability to ignore distracting information). The present study investigated the unity and diversity of inhibition as a psychometric construct, and tested the hypothesis of an inhibition deficit in older age. We measured inhibition in young and old adults with 11 established laboratory tasks: antisaccade, stop-signal, color Stroop, number Stroop, arrow flanker, letter flanker, Simon, global-local, positive and negative compatibility tasks, and n-2 repetition costs in task switching. In both age groups, the inhibition measures from individual tasks had good reliabilities, but correlated only weakly among each other. Structural equation modeling identified a 2-factor model with factors for inhibition of prepotent responses and resistance to distracter interference. Older adults scored worse in the inhibition of prepotent response, but better in the resistance to distracter interference. However, the model had low explanatory power. Together, these findings call into question inhibition as a psychometric construct and the hypothesis of an inhibition deficit in older age. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

    NARCIS (Netherlands)

    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

  5. Performance Monitoring and Response Inhibition in a Saccadic Countermanding Task in High and Low proficient bilinguals.

    Directory of Open Access Journals (Sweden)

    Niharika eSingh

    2015-01-01

    Full Text Available We compared Hindi-English bilinguals differing in their L2 fluency on a saccadic countermanding task which taps inhibitory control as well as monitoring. We particularly explored whether response inhibition and performance monitoring within the oculomotor domain are affected by language proficiency in bilinguals. There were two different oculomotor redirect tasks: Visually Guided Redirect (VGR task (Experiment1 and Memory Guided Redirect (MGR task (Experiment 2. In this task typically a target is presented to which subject must make saccade (No step trials, unless a new target appears on the other location after some delay from the first target onset (Step trials. On such trials participants are required to inhibit and cancel the saccade to the first instead program a saccade to the new target. Using trial switch reaction time (TSRT, which is the time taken to inhibit the initiated saccade to the first target, as a measure of response inhibition, and post-stop slowing as a measure of performance monitoring, we observed two important results. It was found that high proficiency bilinguals showed more post-stop slowing on the no-step trials as compared to the low proficiency bilinguals for both VGR and MGR. Secondly, high and low proficiency bilingual exhibited comparable TSRT in both VGR and MGR, showing no altering effect of language proficiency on the response inhibition in bilinguals. These results suggest that bilingualism impacts performance monitoring which is modulated by language proficiency if not the inhibitory control system. Higher fluency may lead to superior cognitive flexibility, and ability to adjust behaviour that facilitates attainment of cognitive goal. These findings are in consonance with other current studies that suggest a top-down effect of bilingualism on action control systems.

  6. Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR.

    Science.gov (United States)

    Danyal, Karamatullah; de Jong, Willem; O'Brien, Edmund; Bauer, Robert A; Heppner, David E; Little, Andrew C; Hristova, Milena; Habibovic, Aida; van der Vliet, Albert

    2016-11-01

    Acrolein is a major thiol-reactive component of cigarette smoke (CS) that is thought to contribute to increased asthma incidence associated with smoking. Here, we explored the effects of acute acrolein exposure on innate airway responses to two common airborne allergens, house dust mite and Alternaria alternata, and observed that acrolein exposure of C57BL/6 mice (5 ppm, 4 h) dramatically inhibited innate airway responses to subsequent allergen challenge, demonstrated by attenuated release of the epithelial-derived cytokines IL-33, IL-25, and IL-1α. Acrolein and other anti-inflammatory thiol-reactive electrophiles, cinnamaldehyde, curcumin, and sulforaphane, similarly inhibited allergen-induced production of these cytokines from human or murine airway epithelial cells in vitro. Based on our previous observations indicating the importance of Ca 2+ -dependent signaling, activation of the NADPH oxidase DUOX1, and Src/EGFR-dependent signaling in allergen-induced epithelial secretion of these cytokines, we explored the impact of acrolein on these pathways. Acrolein and other thiol-reactive electrophiles were found to dramatically prevent allergen-induced activation of DUOX1 as well as EGFR, and acrolein was capable of inhibiting EGFR tyrosine kinase activity via modification of C797. Biotin-labeling strategies indicated increased cysteine modification and carbonylation of Src, EGFR, as well as DUOX1, in response to acrolein exposure in vitro and in vivo, suggesting that direct alkylation of these proteins on accessible cysteine residues may be responsible for their inhibition. Collectively, our findings indicate a novel anti-inflammatory mechanism of CS-derived acrolein and other thiol-reactive electrophiles, by directly inhibiting DUOX1- and EGFR-mediated airway epithelial responses to airborne allergens. Copyright © 2016 the American Physiological Society.

  7. Sorafenib enhances proteasome inhibitor-mediated cytotoxicity via inhibition of unfolded protein response and keratin phosphorylation

    International Nuclear Information System (INIS)

    Honma, Yuichi; Harada, Masaru

    2013-01-01

    Hepatocellular carcinoma (HCC) is highly resistant to conventional systemic therapies and prognosis for advanced HCC patients remains poor. Recent studies of the molecular mechanisms responsible for tumor initiation and progression have identified several potential molecular targets in HCC. Sorafenib is a multi-kinase inhibitor shown to have survival benefits in advanced HCC. It acts by inhibiting the serine/threonine kinases and the receptor type tyrosine kinases. In preclinical experiments sorafenib had anti-proliferative activity in hepatoma cells and it reduced tumor angiogenesis and increased apoptosis. Here, we demonstrate for the first time that the cytotoxic mechanisms of sorafenib include its inhibitory effects on protein ubiquitination, unfolded protein response (UPR) and keratin phosphorylation in response to endoplasmic reticulum (ER) stress. Moreover, we show that combined treatment with sorafenib and proteasome inhibitors (PIs) synergistically induced a marked increase in cell death in hepatoma- and hepatocyte-derived cells. These observations may open the way to potentially interesting treatment combinations that may augment the effect of sorafenib, possibly including drugs that promote ER stress. Because sorafenib blocked the cellular defense mechanisms against hepatotoxic injury not only in hepatoma cells but also in hepatocyte-derived cells, we must be careful to avoid severe liver injury. -- Graphical abstract: Display Omitted -- Highlights: •We examined the cytotoxic mechanisms of sorafenib in hepatoma cells. •Sorafenib induces cell death via apoptotic and necrotic fashion. •Sorafenib inhibits protein ubiquitination and unfolded protein response. •Autophagy induced by sorafenib may affect its cytotoxicity. •Sorafenib inhibits keratin phosphorylation and cytoplasmic inclusion formation

  8. Neuronal inhibition and excitation, and the dichotomic control of brain hemodynamic and oxygen responses

    DEFF Research Database (Denmark)

    Lauritzen, Martin; Mathiesen, Claus; Schaefer, Katharina

    2012-01-01

    under most conditions correlate to excitation of inhibitory interneurons, but there are important exceptions to that rule as described in this paper. Thus, variations in the balance between synaptic excitation and inhibition contribute dynamically to the control of metabolic and hemodynamic responses...

  9. Prepulse Inhibition of Auditory Cortical Responses in the Caudolateral Superior Temporal Gyrus in Macaca mulatta.

    Science.gov (United States)

    Chen, Zuyue; Parkkonen, Lauri; Wei, Jingkuan; Dong, Jin-Run; Ma, Yuanye; Carlson, Synnöve

    2018-04-01

    Prepulse inhibition (PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the PPI of cortical responses. We recorded local field potentials (LFPs) in four monkeys and investigated whether the PPI of auditory cortical responses (alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyrus (STGcb). We also investigated whether the presence of a conspecific, which draws attention away from the auditory stimuli, affects the PPI of auditory cortical responses. The PPI paradigm consisted of Pulse-only and Prepulse + Pulse trials that were presented randomly while the monkey was alone (ALONE) and while another monkey was present in the same room (ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related inhibition of the N1 amplitude of the evoked responses and cortical oscillations to the Pulse were not affected by the presence of a conspecific. In contrast, gamma oscillations and the amplitude of the N1 response to Pulse-only were suppressed in the ACCOMP condition compared to the ALONE condition. These findings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is a pre-attentive inhibitory process that is independent of attentional modulation.

  10. Segregating Top-Down Selective Attention from Response Inhibition in a Spatial Cueing Go/NoGo Task: An ERP and Source Localization Study.

    Science.gov (United States)

    Hong, Xiangfei; Wang, Yao; Sun, Junfeng; Li, Chunbo; Tong, Shanbao

    2017-08-29

    Successfully inhibiting a prepotent response tendency requires the attentional detection of signals which cue response cancellation. Although neuroimaging studies have identified important roles of stimulus-driven processing in the attentional detection, the effects of top-down control were scarcely investigated. In this study, scalp EEG was recorded from thirty-two participants during a modified Go/NoGo task, in which a spatial-cueing approach was implemented to manipulate top-down selective attention. We observed classical event-related potential components, including N2 and P3, in the attended condition of response inhibition. While in the ignored condition of response inhibition, a smaller P3 was observed and N2 was absent. The correlation between P3 and CNV during the foreperiod suggested an inhibitory role of P3 in both conditions. Furthermore, source analysis suggested that P3 generation was mainly localized to the midcingulate cortex, and the attended condition showed increased activation relative to the ignored condition in several regions, including inferior frontal gyrus, middle frontal gyrus, precentral gyrus, insula and uncus, suggesting that these regions were involved in top-down attentional control rather than inhibitory processing. Taken together, by segregating electrophysiological correlates of top-down selective attention from those of response inhibition, our findings provide new insights in understanding the neural mechanisms of response inhibition.

  11. Competitive inhibition can linearize dose-response and generate a linear rectifier.

    Science.gov (United States)

    Savir, Yonatan; Tu, Benjamin P; Springer, Michael

    2015-09-23

    Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier-that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated.

  12. Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Serk In, E-mail: serkin@korea.edu [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); The BK21 Plus Program for Biomedical Sciences, Korea University College of Medicine, Seoul (Korea, Republic of); Department of Medicine and Center for Bone Biology, Vanderbilt University School of Medicine, Nashville, TN (United States); Park, Sung-Jun [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Laboratory of Obesity and Aging Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Park, Yun Gyu, E-mail: parkyg@korea.ac.kr [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2016-01-15

    The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

  13. Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

    International Nuclear Information System (INIS)

    Park, Serk In; Park, Sung-Jun; Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won; Park, Yun Gyu

    2016-01-01

    The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

  14. Separating the Fish from the Sharks: A Longitudinal Study of Preschool Response Inhibition

    Science.gov (United States)

    Wiebe, Sandra A.; Sheffield, Tiffany D.; Espy, Kimberly Andrews

    2012-01-01

    The development of response inhibition was investigated using a computerized go/no-go task, in a lagged sequential design where 376 preschool children were assessed repeatedly between 3.0 and 5.25 years of age. Growth curve modeling was used to examine change in performance and predictors of individual differences. The most pronounced change was…

  15. Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.

    Science.gov (United States)

    Yamamoto, Shunsuke; Ohta, Noriyuki; Matsumoto, Atsuhiro; Horiguchi, Yu; Koide, Moe; Fujino, Yuji

    2016-02-04

    BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor.

  16. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.

    Science.gov (United States)

    Borbély, Sándor; Jócsák, Gergely; Moldován, Kinga; Sedlák, Éva; Preininger, Éva; Boldizsár, Imre; Tóth, Attila; Atlason, Palmi T; Molnár, Elek; Világi, Ildikó

    2016-07-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Nuclear accident/radiological emergency assistance plan. NAREAP - edition 2000. Emergency preparedness and response

    International Nuclear Information System (INIS)

    2000-01-01

    The purpose of the Nuclear Accident/Radiological Emergency Assistance Plan (NAREAP) is to describe the framework for systematic, integrated, co-ordinated, and effective preparedness and response for a nuclear accident or radiological emergency involving facilities or practices that may give rise to a threat to health, the environment or property. The purpose of the NAREAP is: to define the emergency response objectives of the Agency's staff in a nuclear accident or a radiological emergency; to assign responsibilities for performing the tasks and authorities for making the decisions that comprise the Agency staff's response to a nuclear accident or radiological emergency; to guide the Agency managers who must ensure that all necessary tasks are given the necessary support in discharging the Agency staff responsibilities and fulfilling its obligations in response to an emergency; to ensure that the development and maintenance of detailed and coherent response procedures are well founded; to act as a point of reference for individual Agency staff members on their responsibilities (as an individual or a team member) throughout a response; to identify interrelationships with other international intergovernmental Organizations; and to serve as a training aid to maintain readiness of personnel. The NAREAP refers to the arrangements of the International Atomic Energy Agency and of the United Nations Security and Safety Section at the Vienna International Centre (UNSSS-VIC) that may be necessary for the IAEA to respond to a nuclear accident or radiological emergency, as defined in the Early Notification and Assistance Conventions. It covers response arrangements for any situation that may have actual, potential or perceived radiological consequences and that could require a response from the IAEA, as well as the arrangements for developing, maintaining and exercising preparedness. The implementing procedures themselves are not included in the NAREAP, but they are required

  18. Extinction produces context inhibition and multiple-context extinction reduces response recovery in human predictive learning.

    Science.gov (United States)

    Glautier, Steven; Elgueta, Tito; Nelson, James Byron

    2013-12-01

    Two experiments with human participants were used to investigate recovery of an extinguished learned response after a context change using ABC designs. In an ABC design, the context changes over the three successive stages of acquisition (context A), extinction (context B), and test (context C). In both experiments, we found reduced recovery in groups that had extinction in multiple contexts, and that the extinction contexts acquired inhibitory strength. These results confirm those of previous investigations, that multiple-context extinction can produce less response recovery than single-context extinction, and they also provide new evidence for the involvement of contextual inhibitory processes in extinction in humans. The foregoing results are broadly in line with a protection-from-extinction account of response recovery. Yet, despite the fact that we detected contextual inhibition, predictions based on protection-from-extinction were not fully reliable for the single- and multiple-context group differences that we observed in (1) rates of extinction and (2) the strength of context inhibition. Thus, although evidence was obtained for a protection-from-extinction account of response recovery, this account can not explain all of the data.

  19. Influence of DAT1 and COMT variants on neural activation during response inhibition in adolescents with attention-deficit/hyperactivity disorder and healthy controls

    NARCIS (Netherlands)

    van Rooij, D.; Hoekstra, P. J.; Bralten, J.; Hakobjan, M.; Oosterlaan, J.; Franke, B.; Rommelse, N.; Buitelaar, J. K.; Hartman, C. A.

    2015-01-01

    Background. Impairment of response inhibition has been implicated in attention-deficit/hyperactivity disorder (ADHD). Dopamine neurotransmission has been linked to the behavioural and neural correlates of response inhibition. The current study aimed to investigate the relationship of polymorphisms

  20. Response inhibition in borderline personality disorder: event-related potentials in a Go/Nogo task.

    Science.gov (United States)

    Ruchsow, M; Groen, G; Kiefer, M; Buchheim, A; Walter, H; Martius, P; Reiter, M; Hermle, L; Spitzer, M; Ebert, D; Falkenstein, M

    2008-01-01

    Borderline personality disorder (BPD) has been related to a dysfunction of anterior cingulate cortex, amygdala, and prefrontal cortex and has been associated clinically with impulsivity, affective instability, and significant interpersonal distress. We examined 17 patients with BPD and 17 age-, sex-, and education matched control participants with no history of Axis I or II psychopathology using event-related potentials (ERPs). Participants performed a hybrid flanker-Go/Nogo task while multichannel EEG was recorded. Our study focused on two ERP components: the Nogo-N2 and the Nogo-P3, which have been discussed in the context of response inhibition and response conflict. ERPs were computed on correct Go trials (button press) and correct Nogo trials (no button press), separately. Groups did not differ with regard to the Nogo-N2. However, BPD patients showed reduced Nogo-P3 amplitudes. For the entire group (n = 34) we found a negative correlation with the Barratt Impulsiveness Scale (BIS-10) and Becks's depression inventory (BDI). The present study is the first to examine Nogo-N2 and Nogo-P3 in BPD and provides further evidence for impaired response inhibition in BPD patients.

  1. Contextual startle responses moderate the relation between behavioral inhibition and anxiety in middle childhood.

    Science.gov (United States)

    Barker, Tyson V; Reeb-Sutherland, Bethany; Degnan, Kathryn A; Walker, Olga L; Chronis-Tuscano, Andrea; Henderson, Heather A; Pine, Daniel S; Fox, Nathan A

    2015-11-01

    Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has examined relations among BI, startle responsivity, and anxiety in a prospective manner. Data for the present study were from a longitudinal study of infant temperament. Maternal reports and observations of BI were assessed at ages 2 and 3. At age 7, participants completed a startle procedure, while electromyography was collected, where participants viewed different colors on a screen that were associated with either the delivery of an aversive stimulus (i.e., puff of air to the larynx; threat cue) or the absence of the aversive stimulus (i.e., safety cue). Parental reports of child anxiety were collected when children were 7 and 9 years of age. Results revealed that startle responses at age 7 moderated the relation between early BI and 9-year anxiety. These findings provide insight into one potential mechanism that may place behaviorally inhibited children at risk for anxiety. © 2015 Society for Psychophysiological Research.

  2. Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo.

    Science.gov (United States)

    Koo, G C; Blake, J T; Talento, A; Nguyen, M; Lin, S; Sirotina, A; Shah, K; Mulvany, K; Hora, D; Cunningham, P; Wunderler, D L; McManus, O B; Slaughter, R; Bugianesi, R; Felix, J; Garcia, M; Williamson, J; Kaczorowski, G; Sigal, N H; Springer, M S; Feeney, W

    1997-06-01

    The voltage activated K+ channel (Kv1.3) has recently been identified as the molecule that sets the resting membrane potential of peripheral human T lymphoid cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell activation, suggesting that Kv1.3 may be a target for immunosuppression. However, despite the in vitro evidence, there has been no in vivo demonstration that blockade of Kv1.3 will attenuate an immune response. The difficulty is due to species differences, as the channel does not set the membrane potential in rodent peripheral T cells. In this study, we show that the channel is present on peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin, we demonstrate that Kv1.3 also regulates the resting membrane potential, and that blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge. In addition, prolonged Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic development of T cell subsets. These results provide in vivo evidence that Kv1.3 is a novel target for immunomodulation.

  3. Decreased response inhibition to sad faces during explicit and implicit tasks in females with depression: Evidence from an event-related potential study.

    Science.gov (United States)

    Yu, Fengqiong; Zhou, Xiaoqing; Qing, Wu; Li, Dan; Li, Jing; Chen, Xingui; Ji, Gongjun; Dong, Yi; Luo, Yuejia; Zhu, Chunyan; Wang, Kai

    2017-01-30

    The present study aimed to investigate neural substrates of response inhibition to sad faces across explicit and implicit tasks in depressed female patients. Event-related potentials were obtained while participants performed modified explicit and implicit emotional go/no-go tasks. Compared to controls, depressed patients showed decreased discrimination accuracy and amplitudes of original and nogo-go difference waves at the P3 interval in response inhibition to sad faces during explicit and implicit tasks. P3 difference wave were positively correlated with discrimination accuracy and were independent of clinical assessment. The activation of right dorsal prefrontal cortex was larger for the implicit than for the explicit task in sad condition in health controls, but was similar for the two tasks in depressed patients. The present study indicated that selectively impairment in response inhibition to sad faces in depressed female patients occurred at the behavior inhibition stage across implicit and explicit tasks and may be a trait-like marker of depression. Longitudinal studies are required to determine whether decreased response inhibition to sad faces increases the risk for future depressive episodes so that appropriate treatment can be administered to patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Interactive effects of music and prefrontal cortex stimulation in modulating response inhibition

    OpenAIRE

    Mansouri, Farshad Alizadeh; Acevedo, Nicola; Illipparampil, Rosin; Fehring, Daniel J.; Fitzgerald, Paul B.; Jaberzadeh, Shapour

    2017-01-01

    Influential hypotheses propose that alterations in emotional state influence decision processes and executive control of behavior. Both music and transcranial direct current stimulation (tDCS) of prefrontal cortex affect emotional state, however interactive effects of music and tDCS on executive functions remain unknown. Learning to inhibit inappropriate responses is an important aspect of executive control which is guided by assessing the decision outcomes such as errors. We found that high-...

  5. The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Gottschalk, Sanne; Ifrah, Dan; Lerche, Sandra

    2013-01-01

    the growth of S. aureus without ATP leakage. Instead, LP5 bound DNA and inhibited macromolecular synthesis. The binding to DNA also led to inhibition of DNA gyrase and topoisomerase IV and caused induction of the SOS response. CONCLUSIONS: Our data demonstrate that LP5 may have a dual mode of action against...

  6. PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

    Science.gov (United States)

    Xu, Benjamin; Sandrini, Marco; Wang, Wen-Tung; Smith, Jason F; Sarlls, Joelle E; Awosika, Oluwole; Butman, John A; Horwitz, Barry; Cohen, Leonardo G

    2016-09-01

    Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

    Science.gov (United States)

    Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

    2014-03-01

    Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

  8. Joint Planning Of Energy Storage and Transmission Considering Wind-Storage Combined System and Demand Side Response

    Science.gov (United States)

    Huang, Y.; Liu, B. Z.; Wang, K. Y.; Ai, X.

    2017-12-01

    In response to the new requirements of the operation mode of wind-storage combined system and demand side response for transmission network planning, this paper presents a joint planning of energy storage and transmission considering wind-storage combined system and demand side response. Firstly, the charge-discharge strategy of energy storage system equipped at the outlet of wind farm and demand side response strategy are analysed to achieve the best comprehensive benefits through the coordination of the two. Secondly, in the general transmission network planning model with wind power, both energy storage cost and demand side response cost are added to the objective function. Not only energy storage operation constraints and but also demand side response constraints are introduced into the constraint condition. Based on the classical formulation of TEP, a new formulation is developed considering the simultaneous addition of the charge-discharge strategy of energy storage system equipped at the outlet of the wind farm and demand side response strategy, which belongs to a typical mixed integer linear programming model that can be solved by mature optimization software. The case study based on the Garver-6 bus system shows that the validity of the proposed model is verified by comparison with general transmission network planning model. Furthermore, the results demonstrate that the joint planning model can gain more economic benefits through setting up different cases.

  9. Monetary Reward and Punishment to Response Inhibition Modulate Activation and Synchronization Within the Inhibitory Brain Network

    Directory of Open Access Journals (Sweden)

    Rupesh K. Chikara

    2018-03-01

    Full Text Available A reward or punishment can modulate motivation and emotions, which in turn affect cognitive processing. The present simultaneous functional magnetic resonance imaging-electroencephalography study examines neural mechanisms of response inhibition under the influence of a monetary reward or punishment by implementing a modified stop-signal task in a virtual battlefield scenario. The participants were instructed to play as snipers who open fire at a terrorist target but withhold shooting in the presence of a hostage. The participants performed the task under three different feedback conditions in counterbalanced order: a reward condition where each successfully withheld response added a bonus (i.e., positive feedback to the startup credit, a punishment condition where each failure in stopping deduced a penalty (i.e., negative feedback, and a no-feedback condition where response outcome had no consequences and served as a control setting. Behaviorally both reward and punishment conditions led to significantly down-regulated inhibitory function in terms of the critical stop-signal delay. As for the neuroimaging results, increased activities were found for the no-feedback condition in regions previously reported to be associated with response inhibition, including the right inferior frontal gyrus and the pre-supplementary motor area. Moreover, higher activation of the lingual gyrus, posterior cingulate gyrus (PCG and inferior parietal lobule were found in the reward condition, while stronger activation of the precuneus gyrus was found in the punishment condition. The positive feedback was also associated with stronger changes of delta, theta, and alpha synchronization in the PCG than were the negative or no-feedback conditions. These findings depicted the intertwining relationship between response inhibition and motivation networks.

  10. Implementation Plan for a Common Nordic Retail Market. Evaluation of the responses on the public consultation

    Energy Technology Data Exchange (ETDEWEB)

    2010-09-15

    Draft implementation plan for a common Nordic Retail Market was developed in close cooperation with relevant stakeholders in the Nordic electricity market during winter and spring 2010. The implementation plan outlines what should be done, by whom and when in order to create a common Nordic end user market over the coming years. NordREG organised a public consultation on the draft implementation plan from the end of June until the beginning of the August, 2010 and received 25 responses from stakeholders. This evaluation report includes summary of stakeholders' responses and NordREG comments on stakeholders' views. The evaluation of the responses has been taken into account during the finalization of the implementation plan

  11. Compliance with federal and state regulations regarding the emergency response plan and physical security plan at the Oregon State TRIGA reactor

    International Nuclear Information System (INIS)

    Johnson, A.G.; Ringle, J.C.; Anderson, T.V.

    1976-01-01

    Recent legislative actions within the State of Oregon have had a significant impact upon the OSU TRIGA Emergency Response Plan, and to a lesser extent upon the Physical Security Plan. These state imposed changes will be reviewed in light of existing federal requirements. With the upcoming acquisition of FLIP fuel in August 1976, NRC required several major changes to the existing Physical Security Plan. Within the limitations of public disclosure, these changes will be contrasted to the present plan. (author)

  12. Tanshinone IIA attenuates neuropathic pain via inhibiting glial activation and immune response.

    Science.gov (United States)

    Cao, Fa-Le; Xu, Min; Wang, Yan; Gong, Ke-Rui; Zhang, Jin-Tao

    2015-01-01

    Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord. Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Planning and Response to the Detonation of an Improvised Nuclear Device: Past, Present, and Future Research

    Energy Technology Data Exchange (ETDEWEB)

    Bentz, A

    2008-07-31

    While the reality of an improvised nuclear device (IND) being detonated in an American city is unlikely, its destructive power is such that the scenario must be planned for. Upon reviewing the academic literature on the effects of and response to IND events, this report looks to actual responders from around the country. The results from the meetings of public officials in the cities show where gaps exist between theoretical knowledge and actual practice. In addition to the literature, the meetings reveal areas where future research needs to be conducted. This paper recommends that local response planners: meet to discuss the challenges of IND events; offer education to officials, the public, and responders on IND events; incorporate 'shelter-first' into response plans; provide information to the public and responders using the 3 Cs; and engage the private sector (including media) in response plans. In addition to these recommendations for the response planners, the paper provides research questions that once answered will improve response plans around the country. By following the recommendations, both groups, response planners and researchers, can help the country better prepare for and mitigate the effects of an IND detonation.

  14. Planning and Response to the Detonation of an Improvised Nuclear Device: Past, Present, and Future Research

    International Nuclear Information System (INIS)

    Bentz, A.

    2008-01-01

    While the reality of an improvised nuclear device (IND) being detonated in an American city is unlikely, its destructive power is such that the scenario must be planned for. Upon reviewing the academic literature on the effects of and response to IND events, this report looks to actual responders from around the country. The results from the meetings of public officials in the cities show where gaps exist between theoretical knowledge and actual practice. In addition to the literature, the meetings reveal areas where future research needs to be conducted. This paper recommends that local response planners: meet to discuss the challenges of IND events; offer education to officials, the public, and responders on IND events; incorporate 'shelter-first' into response plans; provide information to the public and responders using the 3 Cs; and engage the private sector (including media) in response plans. In addition to these recommendations for the response planners, the paper provides research questions that once answered will improve response plans around the country. By following the recommendations, both groups, response planners and researchers, can help the country better prepare for and mitigate the effects of an IND detonation

  15. Individual differences in heart rate variability predict the degree of slowing during response inhibition and initiation in the presence of emotional stimuli.

    Directory of Open Access Journals (Sweden)

    Angelos-Miltiadis eKrypotos

    2011-10-01

    Full Text Available Response inhibition is a hallmark of executive control and crucial to support flexible behaviour in a constantly changing environment. Recently, it has been shown that response inhibition is influenced by the presentation of emotional stimuli (Verbruggen and De Houwer, 2007. Healthy individuals typically differ in the degree to which they are able to regulate their emotional state, but it remains unknown whether individual differences in emotion regulation (ER may alter the interplay between emotion and response inhibition. Here we address this issue by testing healthy volunteers who were equally divided in groups with high and low Heart Rate Variability (HRV during rest, a physiological measure that serves as proxy of emotion regulation. Both groups performed an emotional stop-signal task, in which negative high arousing pictures served as negative emotional stimuli and neutral low arousing pictures served as neutral non-emotional stimuli. We found that individuals with high HRV activated and inhibited their responses faster compared to individuals with low HRV, but only in the presence of negative stimuli. No group differences emerged for the neutral stimuli. Thus, individuals with low HRV are more susceptible to the adverse effects of negative emotion on response initiation and inhibition. The present research corroborates the idea that the presentation of emotional stimuli may interfere with inhibition and it also adds to previous research by demonstrating that the aforementioned relationship varies for individuals differing in HRV. We suggest that focusing on individual differences in HRV and its associative ER may shed more light on the dynamic interplay between emotion and cognition.

  16. Food-specific response inhibition, dietary restraint and snack intake in lean and overweight/obese adults: a moderated-mediation model.

    Science.gov (United States)

    Price, M; Lee, M; Higgs, S

    2016-05-01

    The relationship between response inhibition and obesity is currently unclear. This may be because of inconsistencies in methodology, design limitations and the use of narrow samples. In addition, dietary restraint has not been considered, yet restraint has been reported to moderate performance on behavioural tasks of response inhibition. The aim of this study was to investigate performance on both a food-based and a neutral stimuli go/no-go task, which addresses current design limitations, in lean and overweight/obese adults. The moderating role of dietary restraint in the relationship between body composition, response inhibition and snack intake was also measured. Lean and overweight/obese, males and females (N=116) completed both a food-based and neutral category control go/no-go task, in a fully counterbalanced repeated-measures design. A bogus taste-test was then completed, followed by a self-report measure of dietary restraint. PROCESS moderated-mediation analysis showed that overweight/obese, compared with lean, participants made more errors on the food-based (but not the neutral) go/no-go task, but only when they were low in dietary restraint. Performance on the food-based go/no-go task predicted snack intake across the sample. Increased intake in the overweight, low restrainers was fully mediated by increased errors on the food-based (but not the neutral) go/no-go task. Distinguishing between high and low restrained eaters in the overweight/obese population is crucial in future obesity research incorporating food-based go/no-go tasks. Poor response inhibition to food cues predicts overeating across weight groups, suggesting weight loss interventions and obesity prevention programmes should target behavioural inhibition training in such individuals.

  17. Addressing the gap between public health emergency planning and incident response

    Science.gov (United States)

    Freedman, Ariela M; Mindlin, Michele; Morley, Christopher; Griffin, Meghan; Wooten, Wilma; Miner, Kathleen

    2013-01-01

    Objectives: Since 9/11, Incident Command System (ICS) and Emergency Operations Center (EOC) are relatively new concepts to public health, which typically operates using less hierarchical and more collaborative approaches to organizing staff. This paper describes the 2009 H1N1 influenza outbreak in San Diego County to explore the use of ICS and EOC in public health emergency response. Methods: This study was conducted using critical case study methodology consisting of document review and 18 key-informant interviews with individuals who played key roles in planning and response. Thematic analysis was used to analyze data. Results: Several broad elements emerged as key to ensuring effective and efficient public health response: 1) developing a plan for emergency response; 2) establishing the framework for an ICS; 3) creating the infrastructure to support response; 4) supporting a workforce trained on emergency response roles, responsibilities, and equipment; and 5) conducting regular preparedness exercises. Conclusions: This research demonstrates the value of investments made and that effective emergency preparedness requires sustained efforts to maintain personnel and material resources. By having the infrastructure and experience based on ICS and EOC, the public health system had the capability to surge-up: to expand its day-to-day operation in a systematic and prolonged manner. None of these critical actions are possible without sustained funding for the public health infrastructure. Ultimately, this case study illustrates the importance of public health as a key leader in emergency response. PMID:28228983

  18. Oak Ridge National Laboratory Corrective Action Plan in response to Tiger Team assessment

    International Nuclear Information System (INIS)

    1991-01-01

    This report presents a complete response to the Tiger Team assessment that was conducted at Oak Ridge National Laboratory (ORNL) and at the US Department of Energy (DOE) Oak Ridge Operations Office (ORO) from October 22, 1990, through November 30, 1990. The action plans have undergone both a discipline review and a cross-cutting review with respect to root cause. In addition, the action plans have been integrated with initiatives being pursued across Martin Marietta Energy Systems, Inc., in response to Tiger Team findings at other DOE facilities operated by Energy Systems. The root cause section is complete and describes how ORNL intends to address the root causes of the findings identified during the assessment. The action plan has benefited from a complete review by various offices at DOE Headquarters as well as review by the Tiger Team that conducted the assessment to ensure that the described actions are responsive to the observed problems

  19. Oak Ridge National Laboratory Corrective Action Plan in response to Tiger Team assessment

    Energy Technology Data Exchange (ETDEWEB)

    Kuliasha, Michael A.

    1991-08-23

    This report presents a complete response to the Tiger Team assessment that was conducted at Oak Ridge National Laboratory (ORNL) and at the US Department of Energy (DOE) Oak Ridge Operations Office (ORO) from October 22, 1990, through November 30, 1990. The action plans have undergone both a discipline review and a cross-cutting review with respect to root cause. In addition, the action plans have been integrated with initiatives being pursued across Martin Marietta Energy Systems, Inc., in response to Tiger Team findings at other DOE facilities operated by Energy Systems. The root cause section is complete and describes how ORNL intends to address the root causes of the findings identified during the assessment. The action plan has benefited from a complete review by various offices at DOE Headquarters as well as review by the Tiger Team that conducted the assessment to ensure that the described actions are responsive to the observed problems.

  20. Approach to downstream planning for nearshore response and sensitive areas protection outside Prince William Sound, Alaska

    International Nuclear Information System (INIS)

    DeCola, E.G.; Robertson, T.L.; Robertson, R.; Banta, J.

    2004-01-01

    This study assessed the need for an oil spill response plan for downstream coastal communities that could be affected by oil spilled from tankers travelling in Prince William Sound, Alaska. For the purpose of oil spill contingency planning, the State of Alaska has been divided into the Kodiak and Cook Inlet sub-areas that are at risk for downstream impacts from a Prince William Sound oil spill. The 1989 Exxon Valdez oil spill provided an example of a worst-case scenario oil spill from a tanker in Prince William Sound, but the oil spill planning system that has evolved in Alaska does not adequately plan for on oil spill that originates in one sub-area of the state, but impacts other sub-areas in the downstream spill path. This study analyzed the gaps that exist in the current response planning system in the Prince William Sound, Cook Inlet and Kodiak sub-areas. A method was proposed to improve the existing response plans so that emergency response teams are better prepared to manage cross-boundary oil spills originating in Prince William Sound. The proposed method focuses on nearshore response and sensitive areas protection for coastlines and communities that are at risk for oil spills from a tanker travelling the Trans-Alaska Pipeline System (TAPS). 11 refs., 3 figs

  1. Effective connectivity reveals important roles for both the hyperdirect (fronto-subthalamic) and indirect (fronto-striatal-pallidal) fronto-basal ganglia pathways during response inhibition

    NARCIS (Netherlands)

    Jahfari, S.; Waldorp, L.; van den Wildenberg, W.P.M.; Scholte, H.S.; Ridderinkhof, K.R.; Forstmann, B.U.

    2011-01-01

    Fronto-basal ganglia pathways play a crucial role in voluntary action control, including the ability to inhibit motor responses. Response inhibition might be mediated via a fast hyperdirect pathway connecting the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA) with

  2. Squalene Inhibits ATM-Dependent Signaling in γIR-Induced DNA Damage Response through Induction of Wip1 Phosphatase.

    Directory of Open Access Journals (Sweden)

    Naoto Tatewaki

    Full Text Available Ataxia telangiectasia mutated (ATM kinase plays a crucial role as a master controller in the cellular DNA damage response. Inhibition of ATM leads to inhibition of the checkpoint signaling pathway. Hence, addition of checkpoint inhibitors to anticancer therapies may be an effective targeting strategy. A recent study reported that Wip1, a protein phosphatase, de-phosphorylates serine 1981 of ATM during the DNA damage response. Squalene has been proposed to complement anticancer therapies such as chemotherapy and radiotherapy; however, there is little mechanistic information supporting this idea. Here, we report the inhibitory effect of squalene on ATM-dependent DNA damage signals. Squalene itself did not affect cell viability and the cell cycle of A549 cells, but it enhanced the cytotoxicity of gamma-irradiation (γIR. The in vitro kinase activity of ATM was not altered by squalene. However, squalene increased Wip1 expression in cells and suppressed ATM activation in γIR-treated cells. Consistent with the potential inhibition of ATM by squalene, IR-induced phosphorylation of ATM effectors such as p53 (Ser15 and Chk1 (Ser317 was inhibited by cell treatment with squalene. Thus, squalene inhibits the ATM-dependent signaling pathway following DNA damage through intracellular induction of Wip1 expression.

  3. A Comparative Study of Ethylene Growth Response Kinetics in Eudicots and Monocots Reveals a Role for Gibberellin in Growth Inhibition and Recovery1[W][OA

    Science.gov (United States)

    Kim, Joonyup; Wilson, Rebecca L.; Case, J. Brett; Binder, Brad M.

    2012-01-01

    Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa ‘Nipponbare’) seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics. PMID:22977279

  4. Response Inhibition and Its Relationship to Phonological Processing in Children with and without Dyslexia

    Science.gov (United States)

    Schmid, Johanna M.; Labuhn, Andju S.; Hasselhorn, Marcus

    2011-01-01

    This study investigates response inhibition and its relationship to phonological processing in third-graders with and without dyslexia. Children with dyslexia (n = 20) and children without dyslexia (n = 16) were administered a stop signal task and a digit span forwards task. Initial analyses revealed phonological processing deficits in terms of a…

  5. The UK national response plan: An 'all-risk' approach

    International Nuclear Information System (INIS)

    Englefield, C.

    2001-01-01

    Full text: The UK has been using and regulating radioactive materials for many years. The law, and the regulatory systems to implement it have developed over time, to meet the perceived need. More recently, the threat of inadvertent movements of, and illicit trafficking in radioactive materials has become apparent. This relatively new challenge cannot be met by a single U.K. law enforcement body. There will be Police and security services interest in any cases that arise of deliberate trafficking in fissile materials, and there will be statutory concerns for Customs and Excise. At the operational level, they do not have radioanalytical services and radiation protection support immediately available, as the frequency of occurrence of such incidents is extremely low. However, the typical case is an inadvertent movement. These usually involve orphaned sources, where none of the above law enforcement bodies have a statutory locus. In such cases, it is the UK environment agencies that take the lead (as regulators of radioactive substances), together with Health and Safety Executive as regulators of radiation safety. However they do not have all the statutory powers needed to intervene. This is in contrast to the position in some other countries. The UK paper at the International Conference of Regulators in Buenos Aires in December 2000 described the UK's co-ordination work to create synergies between law enforcement bodies and potentially affected industry groups. This was described as an 'All Risk Approach'. This is seen as the best way to manage an effective response to the challenge, given that the legislation cannot at present provide all the necessary powers. This new paper will describe the UK Response Plan and how it is designed to cover all risk: radiological and socio-economic. It will also describe how the Plan is being tested and validated as a project. The plan draws on UK Emergency Planning policy, as well as IAEA guidance on the Prevention, Detection and

  6. Restoring stakeholders’ trust in multinationals’ tax planning practices with corporate social responsibility (CSR)

    NARCIS (Netherlands)

    Jallai, Ave-Geidi; Peeters, Bruno; Gribnau, Hans; Badisco, Jo

    2017-01-01

    This contribution discusses the tax planning behaviour of big corporations and investigates Corporate Social Responsibility (CSR) as a tool to battle the issue. It will be argued that certain legal tax planning strategies of multinationals are not acceptable to local communities and the public in

  7. Effects of childhood trauma on left inferior frontal gyrus function during response inhibition across psychotic disorders.

    Science.gov (United States)

    Quidé, Y; O'Reilly, N; Watkeys, O J; Carr, V J; Green, M J

    2018-07-01

    Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task. We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not. In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity. Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.

  8. 33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

    Science.gov (United States)

    2010-07-01

    ... POLLUTION PREVENTION REGULATIONS FOR VESSELS Tank Vessel Response Plans for Oil § 155.1040 Response plan...-based support or advice; (ii) The individuals who shall be notified of a casualty potentially affecting... coordinator responsible for overseeing or directing those actions. (4) The organizational structure that will...

  9. MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection.

    Science.gov (United States)

    Kim, Jin Kyung; Yuk, Jae-Min; Kim, Soo Yeon; Kim, Tae Sung; Jin, Hyo Sun; Yang, Chul-Su; Jo, Eun-Kyeong

    2015-06-01

    MicroRNAs (miRNAs) are small noncoding nucleotides that play critical roles in the regulation of diverse biological functions, including the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis. Although the pathways associated with autophagy must be tightly regulated at a posttranscriptional level, the contribution of miRNAs and whether they specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that M. tuberculosis infection of macrophages leads to increased expression of miRNA-125a-3p (miR-125a), which targets UV radiation resistance-associated gene (UVRAG), to inhibit autophagy activation and antimicrobial responses to M. tuberculosis. Forced expression of miR-125a significantly blocked M. tuberculosis-induced activation of autophagy and phagosomal maturation in macrophages, and inhibitors of miR-125a counteracted these effects. Both TLR2 and MyD88 were required for biogenesis of miR-125a during M. tuberculosis infection. Notably, activation of the AMP-activated protein kinase significantly inhibited the expression of miR-125a in M. tuberculosis-infected macrophages. Moreover, either overexpression of miR-125a or silencing of UVRAG significantly attenuated the antimicrobial effects of macrophages against M. tuberculosis. Taken together, these data indicate that miR-125a regulates the innate host defense by inhibiting the activation of autophagy and antimicrobial effects against M. tuberculosis through targeting UVRAG. Copyright © 2015 by The American Association of Immunologists, Inc.

  10. Male Smokers' and Non-Smokers' Response Inhibition in Go/No-Go Tasks: Effect of Three Task Parameters

    Science.gov (United States)

    Zhao, Xin; Liu, Xiaoting; Zan, Xiangyi; Jin, Ge; Maes, Joseph H. R.

    2016-01-01

    Impaired response inhibition plays a major role in many addictive behaviors. However, in studies using go/no-go tasks, findings regarding the presence of response inhibition deficits in nicotine-dependent individuals are mixed. This might be due to differences between studies on a number of task parameters. Here we aimed to identify task conditions under which go/no-go task performance deficits can be observed in smokers and to characterize the nature of such deficits. Sixty-one male students (30 smokers, 31 non-smokers) performed a go/no-go task while independently manipulating three task parameters: (1) percentage no-go trials (50% or 25%), (2) stimulus presentation time (600 ms or 200 ms), and (3) nature of no-go stimuli (cigarette related or cigarette unrelated). Three measures, reaction time on go trials and percentage correct responses on go and no-go trials, served as performance indicators. Under 200-ms but not 600-ms stimulus presentation conditions, the smokers responded faster on go trials and made more errors on both go and no-go trials than the non-smokers did. These differences occurred irrespective of the percentage of no-go trials and nature of no-go stimuli. The accuracy differences disappeared after controlling for the response time differences, suggesting a strong speed-accuracy trade-off. This study contributes to unraveling the conditions under which smokers display impaired inhibition performance and helps to characterize the nature of this impairment. Under task conditions prompting fast responding, smokers are more prone to increase response speed and to make more errors than non-smokers. PMID:27500831

  11. Problems related to public perceptions of radiological emergency planning and response

    International Nuclear Information System (INIS)

    Reilly, Margaret A.

    1989-01-01

    Beyond the scientific, the administrative and procedural issues of radiological emergency planning and response there is the issue of public perception. This paper emphasises that, radiation crises being a rare occurrence there is no enough database for generating scholarly quantitative reports. It suggests the need for disseminating timely and accurate information through a single spokesman from a responsible public agency

  12. Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells.

    Directory of Open Access Journals (Sweden)

    Junping Ren

    Full Text Available Human metapneumovirus (hMPV is a leading cause of lower respiratory infection in young children, the elderly and immunocompromised patients. Repeated hMPV infections occur throughout life. However, immune evasion mechanisms of hMPV infection are largely unknown. Recently, our group has demonstrated that hMPV M2-2 protein, an important virulence factor, contributes to immune evasion in airway epithelial cells by targeting the mitochondrial antiviral-signaling protein (MAVS. Whether M2-2 regulates the innate immunity in human dendritic cells (DC, an important family of immune cells controlling antigen presenting, is currently unknown. We found that human DC infected with a virus lacking M2-2 protein expression (rhMPV-ΔM2-2 produced higher levels of cytokines, chemokines and IFNs, compared to cells infected with wild-type virus (rhMPV-WT, suggesting that M2-2 protein inhibits innate immunity in human DC. In parallel, we found that myeloid differentiation primary response gene 88 (MyD88, an essential adaptor for Toll-like receptors (TLRs, plays a critical role in inducing immune response of human DC, as downregulation of MyD88 by siRNA blocked the induction of immune regulatory molecules by hMPV. Since M2-2 is a cytoplasmic protein, we investigated whether M2-2 interferes with MyD88-mediated antiviral signaling. We found that indeed M2-2 protein associated with MyD88 and inhibited MyD88-dependent gene transcription. In this study, we also identified the domains of M2-2 responsible for its immune inhibitory function in human DC. In summary, our results demonstrate that M2-2 contributes to hMPV immune evasion by inhibiting MyD88-dependent cellular responses in human DC.

  13. Emergency response plan for accidents in Saudi Arabia

    International Nuclear Information System (INIS)

    Al-Solaiman, K.M.; Al-Arfaj, A.M.; Farouk, M.A.

    2000-01-01

    This paper presents a brief description of the general emergency plan for accidents involving radioactive materials in the Kingdom of Saudi Arabia. Uses of radioactive materials and radiation sources and their associated potential accident are specified. Most general accident scenarios of various levels have been determined. Protective measures have been specified to reduce individual and collective doses arising during accident situations. Intervention levels for temporary exposure situations, as established in the IAEA's basic safety standards for protection against ionising radiation and for the safety of radiation sources, are adopted as national intervention levels. General procedures for implementation of the response plan, including notification and radiological monitoring instrumentation and equipment, are described and radiation monitoring teams are nominated. Training programs for the different parties which may be called upon to respond are studied and will be started. (author)

  14. Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition.

    Science.gov (United States)

    Guthrie, Michael D; Gilbert, Donald L; Huddleston, David A; Pedapati, Ernest V; Horn, Paul S; Mostofsky, Stewart H; Wu, Steve W

    2018-02-08

    We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) characterization of primary motor cortex (M1) excitability and inhibition. Motor response inhibition prevents unwanted actions and is abnormal in several neuropsychiatric conditions. TMS is a non-invasive technology that can quantify M1 excitability and inhibition using single- and paired-pulse protocols and can be precisely timed to study cortical physiology with high temporal resolution. We modified the original Slater-Hammel (S-H) stop signal task to create a "racecar" version with TMS pulses time-locked to intra-trial events. This task is self-paced, with each trial initiating after a button push to move the racecar towards the 800 ms target. GO trials require a finger-lift to stop the racecar just before this target. Interspersed randomly are STOP trials (25%) during which the dynamically adjusted stop signal prompts subjects to prevent finger-lift. For GO trials, TMS pulses were delivered at 650 ms after trial onset; whereas, for STOP trials, the TMS pulses occurred 150 ms after the stop signal. The timings of the TMS pulses were decided based on electroencephalography (EEG) studies showing event-related changes in these time ranges during stop signal tasks. This task was studied in 3 blocks at two study sites (n=38) and we recorded behavioral performance and event-related motor-evoked potentials (MEP). Regression modelling was used to analyze MEP amplitudes using age as a covariate with multiple independent variables (sex, study site, block, TMS pulse condition [single- vs. paired-pulse], trial condition [GO, successful STOP, failed STOP]). The analysis showed that TMS pulse condition (p<0.0001) and its interaction with trial condition (p=0.009) were significant. Future applications for this online S-H/TMS paradigm include the addition of simultaneous EEG acquisition to measure TMS-evoked EEG potentials. A

  15. Too little, too late or too much, too early? Differential hemodynamics of response inhibition in high and low sensation seekers.

    Science.gov (United States)

    Collins, Heather R; Corbly, Christine R; Liu, Xun; Kelly, Thomas H; Lynam, Donald; Joseph, Jane E

    2012-10-24

    High sensation seeking is associated with strong approach behaviors and weak avoidance responses. The present study used functional magnetic resonance imaging (fMRI) to further characterize the neurobiological underpinnings of this behavioral profile using a Go/No-go task. Analysis of brain activation associated with response inhibition (No-go) versus response initiation and execution (Go) revealed the commonly reported right lateral prefrontal, insula, cingulate, and supplementary motor area network. However, right lateral activation was associated with greater No-go than Go responses only in low sensation seekers. High sensation seekers showed no differential activation in these regions but a more pronounced Go compared to No-go response in several other regions that are involved in salience detection (insula), motor initiation (anterior cingulate) and attention (inferior parietal cortex). Temporal analysis of the hemodynamic response for Go and No-go conditions revealed that the stronger response to Go than No-go trials in high sensation seekers occurred in in the earliest time window in the right middle frontal gyrus, right mid-cingulate and right precuneus. In contrast, the greater No-go than Go response in low sensation seekers occurred in the later time window in these same regions. These findings indicate that high sensation seekers more strongly attend to or process Go trials and show delayed or minimal inhibitory responses on No-go trials in regions that low sensation seekers use for response inhibition. Failure to engage such regions for response inhibition may underlie some of the risky and impulsive behaviors observed in high sensation seekers. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Recovery Sleep Reverses Impaired Response Inhibition due to Sleep Restriction: Evidence from a Visual Event Related Potentials Study.

    Directory of Open Access Journals (Sweden)

    Xiao Jin

    Full Text Available To investigate response inhibition after total sleep deprivation (TSD and the restorative effects of one night of recovery sleep (RS.Fourteen healthy male participants performed a visual Go/NoGo task, and electroencephalogram recordings were conducted at five time points: (1 baseline, (2 after 12 h of TSD, (3 after 24 h of TSD, (4 after 36 h of TSD, and (5 following 8 h of RS. The dynamic changes in response inhibition during TSD and after 8 h of RS were investigated by examining the NoGo-N2 and NoGo-P3 event-related potential components.Compared with baseline, NoGo-P3 amplitudes were decreased, while the NoGo-N2 latency increased along with the awake time prolonged. NoGo anteriorization, which was minimized after 24 h of TSD, progressively decreased with increasing TSD. After 8 h of RS, recoveries of both the NoGo-P3 amplitude and NoGo-N2 latency in the prefrontal cortex were observed compared with the values after 36 h of TSD.TSD induced a dose-dependent functional decline in the response inhibition of NoGo-N2 and NoGo-P3 on prefrontal cortex activation, and 8 h of RS resulted in recovery or maintenance of the response inhibition. However, it was not restored to baseline levels.Participants were chosen male college students only, thus the findings cannot be generalized to older people and women. Additionally, the sample size was small, and, thus, speculations on the meaning of the results of this study should be cautious. The EEG continuous recording should be employed to monitor the decline of alertness following TSD.

  17. 33 CFR 155.1230 - Response plan development and evaluation criteria.

    Science.gov (United States)

    2010-07-01

    ... impact; (2) Oil recovery devices appropriate for the type of animal fats or vegetable oils carried; and (3) Other appropriate equipment necessary to respond to a discharge involving the type of animal fats... VESSELS Response plan requirements for vessels carrying animal fats and vegetable oils as a primary cargo...

  18. Impaired response inhibition and excess cortical thickness as candidate endophenotypes for trichotillomania

    DEFF Research Database (Denmark)

    Odlaug, Brian Lawrence; Chamberlain, Samuel R; Derbyshire, Katie L

    2014-01-01

    occupying an intermediate position. Permutation cluster analysis revealed significant excesses of cortical thickness in patients and their relatives compared to controls, in right inferior/middle frontal gyri (Brodmann Area, BA 47 & 11), right lingual gyrus (BA 18), left superior temporal cortex (BA 21......Trichotillomania is characterized by repetitive pulling out of one's own hair. Impaired response inhibition has been identified in patients with trichotillomania, along with gray matter density changes in distributed neural regions including frontal cortex. The objective of this study...

  19. Technical Basis for Radiological Emergency Plan Annex for WTD Emergency Response Plan: West Point Treatment Plant

    Energy Technology Data Exchange (ETDEWEB)

    Hickey, Eva E.; Strom, Daniel J.

    2005-08-01

    Staff of the King County Wastewater Treatment Division (WTD) have concern about the aftermath of a radiological dispersion event (RDE) leading to the introduction of significant quantities of radioactive material into the combined sanitary and storm sewer system in King County, Washington. Radioactive material could come from the use of a radiological dispersion device (RDD). RDDs include "dirty bombs" that are not nuclear detonations but are explosives designed to spread radioactive material (National Council on Radiation Protection and Measurements (NCRP) 2001). Radioactive material also could come from deliberate introduction or dispersion of radioactive material into the environment, including waterways and water supply systems. This document, Volume 3 of PNNL-15163 is the technical basis for the Annex to the West Point Treatment Plant (WPTP) Emergency Response Plan related to responding to a radiological emergency at the WPTP. The plan primarily considers response to radioactive material that has been introduced in the other combined sanitary and storm sewer system from a radiological dispersion device, but is applicable to any accidental or deliberate introduction of materials into the system.

  20. Assessing the integration of health center and community emergency preparedness and response planning.

    Science.gov (United States)

    Wineman, Nicole V; Braun, Barbara I; Barbera, Joseph A; Loeb, Jerod M

    2007-11-01

    To assess the state of health center integration into community preparedness, we undertook a national study of linkages between health centers and the emergency preparedness and response planning initiatives in their communities. The key objectives of this project were to gain a better understanding of existing linkages in a nationally representative sample of health centers, and identify health center demographic and experience factors that were associated with strong linkages. The objectives of the study were to gain a baseline understanding of existing health center linkages to community emergency preparedness and response systems and to identify factors that were associated with strong linkages. A 60-item questionnaire was mailed to the population of health centers supported by the Health Resources and Services Administration's Bureau of Primary Health Care in February 2005. Results were aggregated and a chi square analysis identified factors associated with stronger linkages. Overall performance on study-defined indicators of strong linkages was low: 34% had completed a hazard vulnerability analysis in collaboration with the community emergency management agency, 30% had their role documented in the community plan, and 24% participated in community-wide exercises. Stronger linkages were associated with experience responding to a disaster and a perception of high risk for experiencing a disaster. The potential for health centers to participate in an integrated response is not fully realized, and their absence from community-based planning leaves an already vulnerable population at greater risk. Community planners should be encouraged to include health centers in planning and response and centers should receive more targeted resources for community integration.

  1. The implementation of the Plan Esperanza and response to the imPACT Review.

    Science.gov (United States)

    Vidaurre, Tatiana; Santos, Carlos; Gómez, Henry; Sarria, Gustavo; Amorin, Edgar; López, Marga; Regalado, Roxana; Manrique, Javier; Tarco, Duniska; Ayestas, Carlos; Calderón, Mónica; Mas, Luis; Neciosup, Silvia; Salazar, Miriam; Chávez, Juan Carlos; Ubillus, Milward; Limache, Abel; Ubillus, José Carlos; Navarro, Jeannie; Sarwal, Kavita; Sutcliffe, Simon; Gutiérrez-Aguado, Alfonso; Silva, Marianela; Mena, Amalia; Guillén, María Eugenia; Castañeda, Carlos; Abugattas, Julio

    2017-10-01

    Following the implementation of the National Cancer Prevention and Control Results-based Budget Programme (PpR Cancer-024) in 2011, the Peruvian Government approved the Plan Esperanza-a population-based national cancer control plan-in 2012. Legislation that ensured full government-supported funding for people who were otherwise unable to access or afford care and treatment accompanied the Plan. In 2013, the Ministry of Health requested an integrated mission of the Programme of Action for Cancer Therapy (imPACT) report to strengthen cancer control in Peru. The imPACT Review, which was executed in 2014, assessed Peru's achievements in cancer control, and areas for improvement, including cancer control planning, further development of population-based cancer registration, increased prevention, early diagnosis, treatment and palliative care, and the engagement and participation of civil society in the health-care system. This Series paper gives a brief history of the development of the Plan Esperanza, describes the innovative funding model that supports it, and summarises how funds are disseminated on the basis of disease, geography, and demographics. An overview of the imPACT Review, and the government's response in the context of the Plan Esperanza, is provided. The development and execution of the Plan Esperanza and the execution of and response to the imPACT Review demonstrates the Peruvian Government's commitment to fighting cancer across the country, including in remote and urban areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients

    DEFF Research Database (Denmark)

    Theander, T G; Svenson, M; Bygbjerg, I C

    1987-01-01

    initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium-derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition...

  3. Anti-WASP intrabodies inhibit inflammatory responses induced by Toll-like receptors 3, 7, and 9, in macrophages

    International Nuclear Information System (INIS)

    Sakuma, Chisato; Sato, Mitsuru; Oshima, Takuma; Takenouchi, Takato; Chiba, Joe; Kitani, Hiroshi

    2015-01-01

    Wiskott-Aldrich syndrome protein (WASP) is an adaptor molecule in immune cells. Recently, we showed that the WASP N-terminal domain interacted with the SH3 domain of Bruton's tyrosine kinase (Btk), and that the complex formed by WASP and Btk was important for TLR2 and TLR4 signaling in macrophages. Several other studies have shown that Btk played important roles in modulating innate immune responses through TLRs in immune cells. Here, we evaluated the significance of the interaction between WASP and Btk in TLR3, TLR7, and TLR9 signaling. We established bone marrow–derived macrophage cell lines from transgenic (Tg) mice that expressed intracellular antibodies (intrabodies) that specifically targeted the WASP N-terminal domain. One intrabody comprised the single-chain variable fragment and the other comprised the light-chain variable region single domain of an anti-WASP N-terminal monoclonal antibody. Both intrabodies inhibited the specific interaction between WASP and Btk, which impaired the expression of TNF-α, IL-6, and IL-1β in response to TLR3, TLR7, or TLR9 stimulation. Furthermore, the intrabodies inhibited the phosphorylation of both nuclear factor (NF)-κB and WASP in response to TLR3, TLR7, or TLR9 stimulation, in the Tg bone marrow-derived macrophages. These results suggested that WASP plays important roles in TLR3, TLR7, and TLR9 signaling by associating with Btk in macrophages. - Highlights: • The interaction between WASP and Btk is critical for TLR3, TLR7, and TLR9 signaling. • Anti-WASP intrabodies inhibited several TLR pathways that led to cytokine expression. • Phosphorylation of NF-κB via TLR signaling was inhibited by anti-WASP intrabodies. • WASP phosphorylation via several TLR ligands was inhibited by anti-WASP intrabodies

  4. Anti-WASP intrabodies inhibit inflammatory responses induced by Toll-like receptors 3, 7, and 9, in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Sakuma, Chisato [Animal Immune and Cell Biology Research Unit, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki, 305-8634 (Japan); Sato, Mitsuru, E-mail: mitsuru.sato@affrc.go.jp [Animal Immune and Cell Biology Research Unit, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki, 305-8634 (Japan); Oshima, Takuma [Department of Biological Science and Technology, Graduate School of Faculty of Industrial Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 (Japan); Takenouchi, Takato [Animal Immune and Cell Biology Research Unit, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki, 305-8634 (Japan); Chiba, Joe [Department of Biological Science and Technology, Graduate School of Faculty of Industrial Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 (Japan); Kitani, Hiroshi [Animal Immune and Cell Biology Research Unit, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki, 305-8634 (Japan)

    2015-02-27

    Wiskott-Aldrich syndrome protein (WASP) is an adaptor molecule in immune cells. Recently, we showed that the WASP N-terminal domain interacted with the SH3 domain of Bruton's tyrosine kinase (Btk), and that the complex formed by WASP and Btk was important for TLR2 and TLR4 signaling in macrophages. Several other studies have shown that Btk played important roles in modulating innate immune responses through TLRs in immune cells. Here, we evaluated the significance of the interaction between WASP and Btk in TLR3, TLR7, and TLR9 signaling. We established bone marrow–derived macrophage cell lines from transgenic (Tg) mice that expressed intracellular antibodies (intrabodies) that specifically targeted the WASP N-terminal domain. One intrabody comprised the single-chain variable fragment and the other comprised the light-chain variable region single domain of an anti-WASP N-terminal monoclonal antibody. Both intrabodies inhibited the specific interaction between WASP and Btk, which impaired the expression of TNF-α, IL-6, and IL-1β in response to TLR3, TLR7, or TLR9 stimulation. Furthermore, the intrabodies inhibited the phosphorylation of both nuclear factor (NF)-κB and WASP in response to TLR3, TLR7, or TLR9 stimulation, in the Tg bone marrow-derived macrophages. These results suggested that WASP plays important roles in TLR3, TLR7, and TLR9 signaling by associating with Btk in macrophages. - Highlights: • The interaction between WASP and Btk is critical for TLR3, TLR7, and TLR9 signaling. • Anti-WASP intrabodies inhibited several TLR pathways that led to cytokine expression. • Phosphorylation of NF-κB via TLR signaling was inhibited by anti-WASP intrabodies. • WASP phosphorylation via several TLR ligands was inhibited by anti-WASP intrabodies.

  5. Dissociable neural effects of stimulus valence and preceding context during the inhibition of responses to emotional faces.

    Science.gov (United States)

    Schulz, Kurt P; Clerkin, Suzanne M; Halperin, Jeffrey M; Newcorn, Jeffrey H; Tang, Cheuk Y; Fan, Jin

    2009-09-01

    Socially appropriate behavior requires the concurrent inhibition of actions that are inappropriate in the context. This self-regulatory function requires an interaction of inhibitory and emotional processes that recruits brain regions beyond those engaged by either processes alone. In this study, we isolated brain activity associated with response inhibition and emotional processing in 24 healthy adults using event-related functional magnetic resonance imaging (fMRI) and a go/no-go task that independently manipulated the context preceding no-go trials (ie, number of go trials) and the valence (ie, happy, sad, and neutral) of the face stimuli used as trial cues. Parallel quadratic trends were seen in correct inhibitions on no-go trials preceded by increasing numbers of go trials and associated activation for correct no-go trials in inferior frontal gyrus pars opercularis, pars triangularis, and pars orbitalis, temporoparietal junction, superior parietal lobule, and temporal sensory association cortices. Conversely, the comparison of happy versus neutral faces and sad versus neutral faces revealed valence-dependent activation in the amygdala, anterior insula cortex, and posterior midcingulate cortex. Further, an interaction between inhibition and emotion was seen in valence-dependent variations in the quadratic trend in no-go activation in the right inferior frontal gyrus and left posterior insula cortex. These results suggest that the inhibition of response to emotional cues involves the interaction of partly dissociable limbic and frontoparietal networks that encode emotional cues and use these cues to exert inhibitory control over the motor, attention, and sensory functions needed to perform the task, respectively. 2008 Wiley-Liss, Inc.

  6. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

    Science.gov (United States)

    Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037

  7. Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pylori

    International Nuclear Information System (INIS)

    Skvarc, Miha; Stubljar, David; Kopitar, Andreja Natasa; Jeverica, Samo; Tepes, Bojan; Kos, Janko; Ihan, Alojz

    2013-01-01

    The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of inhibition of cathepsin X is delayed

  8. Quality Assurance Plan, N springs expedited response action

    International Nuclear Information System (INIS)

    Jackson, G.J.

    1994-01-01

    This document is the Quality Assurance Plan (QAP) to be followed during the definitive design, construction, and operational phases for activities associated with the N Springs Expedited Response Action (ERA) for the 100-NR-2 Operable Unit (OU). Westinghouse Hanford Company (WHC) will comply with the US Department of Energy (DOE) Order 5700.6C, Quality Assurance (DOE 1989), and the US Environmental Protection Agency (EPA), EPA/530-SW-86-031, Technical Guidance Document: Construction Quality Assurance for Hazardous Waste Land Disposal Facilities (EPA 1986)

  9. Do cognitive measures of response inhibition differentiate between attention deficit/hyperactivity disorder and borderline personality disorder?

    NARCIS (Netherlands)

    Dijk, F.E. van; Schellekens, A.F.A.; Broek, P.J.A. van den; Kan, C.C.; Verkes, R.J.; Buitelaar, J.K.

    2014-01-01

    This study examined whether cognitive measures of response inhibition derived from the AX-CPT are able to differentiate between adult attention deficit/hyperactivity disorder (ADHD), borderline personality disorder (BPD), and healthy controls (HC). Current DSM-IV-TR symptoms of ADHD and BPD were

  10. INHIBITION IN SPEAKING PERFORMANCE

    OpenAIRE

    Humaera, Isna

    2015-01-01

    The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

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

    Science.gov (United States)

    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.

  12. Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

    Science.gov (United States)

    Osada, Takuya; Morse, Michael A; Hobeika, Amy; Diniz, Marcio A; Gwin, William R; Hartman, Zachary; Wei, Junping; Guo, Hongtao; Yang, Xiao-Yi; Liu, Cong-Xiao; Kaneko, Kensuke; Broadwater, Gloria; Lyerly, H Kim

    2017-01-01

    Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions. Both preventative and therapeutic Ad-HER3-FL immunization delayed tumor growth but were associated with both intratumoral PD-1 expressing CD8 + T cells and regulatory CD4 + T cell infiltrates. Immune checkpoint inhibition with either anti-PD-1 or anti-PD-L1 antibodies increased intratumoral CD8 + T cell infiltration and eliminated tumor following preventive vaccination with Ad-HER3-FL vaccine. The combination of dual PD-1/PD-L1 and CTLA4 blockade slowed the growth of tumor in response to Ad-HER3-FL in the therapeutic model. We conclude that HER3-targeting vaccines activate HER3-specific T cells and induce anti-HER3 specific antibodies, which alters the intratumoral T cell infiltrate and responses to immune checkpoint inhibition.

  13. Inhibition in movement plan competition: reach trajectories curve away from remembered and task-irrelevant present but not from task-irrelevant past visual stimuli.

    Science.gov (United States)

    Moehler, Tobias; Fiehler, Katja

    2017-11-01

    The current study investigated the role of automatic encoding and maintenance of remembered, past, and present visual distractors for reach movement planning. The previous research on eye movements showed that saccades curve away from locations actively kept in working memory and also from task-irrelevant perceptually present visual distractors, but not from task-irrelevant past distractors. Curvature away has been associated with an inhibitory mechanism resolving the competition between multiple active movement plans. Here, we examined whether reach movements underlie a similar inhibitory mechanism and thus show systematic modulation of reach trajectories when the location of a previously presented distractor has to be (a) maintained in working memory or (b) ignored, or (c) when the distractor is perceptually present. Participants performed vertical reach movements on a computer monitor from a home to a target location. Distractors appeared laterally and near or far from the target (equidistant from central fixation). We found that reaches curved away from the distractors located close to the target when the distractor location had to be memorized and when it was perceptually present, but not when the past distractor had to be ignored. Our findings suggest that automatically encoding present distractors and actively maintaining the location of past distractors in working memory evoke a similar response competition resolved by inhibition, as has been previously shown for saccadic eye movements.

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

    Science.gov (United States)

    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.

  15. Effects of epidermal growth factor receptor kinase inhibition on radiation response in canine osteosarcoma cells.

    Science.gov (United States)

    Mantovani, Fernanda B; Morrison, Jodi A; Mutsaers, Anthony J

    2016-05-31

    Radiation therapy is a palliative treatment modality for canine osteosarcoma, with transient improvement in analgesia observed in many cases. However there is room for improvement in outcome for these patients. It is possible that the addition of sensitizing agents may increase tumor response to radiation therapy and prolong quality of life. Epidermal growth factor receptor (EGFR) expression has been documented in canine osteosarcoma and higher EGFR levels have been correlated to a worse prognosis. However, effects of EGFR inhibition on radiation responsiveness in canine osteosarcoma have not been previously characterized. This study examined the effects of the small molecule EGFR inhibitor erlotinib on canine osteosarcoma radiation responses, target and downstream protein expression in vitro. Additionally, to assess the potential impact of treatment on tumor angiogenesis, vascular endothelial growth factor (VEGF) levels in conditioned media were measured. Erlotinib as a single agent reduced clonogenic survival in two canine osteosarcoma cell lines and enhanced the impact of radiation in one out of three cell lines investigated. In cell viability assays, erlotinib enhanced radiation effects and demonstrated single agent effects. Erlotinib did not alter total levels of EGFR, nor inhibit downstream protein kinase B (PKB/Akt) activation. On the contrary, erlotinib treatment increased phosphorylated Akt in these osteosarcoma cell lines. VEGF levels in conditioned media increased after erlotinib treatment as a single agent and in combination with radiation in two out of three cell lines investigated. However, VEGF levels decreased with erlotinib treatment in the third cell line. Erlotinib treatment promoted modest enhancement of radiation effects in canine osteosarcoma cells, and possessed activity as a single agent in some cell lines, indicating a potential role for EGFR inhibition in the treatment of a subset of osteosarcoma patients. The relative radioresistance of

  16. Savannah River Site management response plan for chemical safety vulnerability field assessment. Revision 1

    International Nuclear Information System (INIS)

    Kahal, E.J.; Murphy, S.L.; Salaymeh, S.R.

    1994-09-01

    As part of the U.S. Department of Energy's (DOE) initiative to identify potential chemical safety vulnerabilities in the DOE complex, the Chemical Safety Vulnerability Core Working Group issued a field verification assessment report. While the report concluded that Savannah River Site (SRS) is moving in a positive direction, the report also identified five chemical safety vulnerabilities with broad programmatic impact that are not easily nor quickly remedied. The May 1994 SRS Management Response Plan addressed the five SRS vulnerabilities identified in the field assessment report. The SRS response plan listed observations supporting the vulnerabilities and any actions taken or planned toward resolution. Many of the observations were resolved by simple explanations, such as the existence of implementation plans for Safety Analysis Report updates. Recognizing that correcting individual observations does not suffice in remedying the vulnerabilities, a task team was assembled to address the broader programmatic issues and to recommend corrective actions

  17. The role of right prefrontal cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation

    NARCIS (Netherlands)

    Dambacher, F.; Sack, A.T.; Lobbestael, J.; Arntz, A.; Brugman, S.; Schuhmann, T.

    2014-01-01

    The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint

  18. Poor response inhibition: at the nexus between substance abuse and attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Groman, Stephanie M; James, Alex S; Jentsch, J David

    2009-05-01

    The co-morbidity between attention deficit hyperactivity disorder (ADHD) and substance abuse and dependence disorders may have multiple causes and consequences. In this review, we will describe neurobehavioral, genetic and animal model studies that support the notion that a common, genetically determined failure of response inhibition function is an endophenotype for both disorders. Through an impairment in the ability to cognitively control pre-potent behaviors, subjects can exhibit a collection of ADHD-like traits (impulsivity and hyperactivity), as well as susceptibility for the initiation of drug taking and its ultimate progression to an inflexible, uncontrollable form. At the neural level, dysfunction within circuitry that includes the ventrolateral frontal and cingulate cortices, as well as in associated basal ganglia zones, contributes to a common pattern of behavioral impairment, explaining aspects of co-morbidity. Animal models of substance abuse/dependence and ADHD that exhibit deficits in response inhibition have substantiated the role of this endophenotype in both disorders and their co-morbidity and should provide a testing ground for interventions targeting it. New directions for research that will further explore this hypothesis and begin to reveal the underlying biological mechanisms will be proposed.

  19. Rule-guided executive control of response inhibition: functional topography of the inferior frontal cortex.

    Directory of Open Access Journals (Sweden)

    Weidong Cai

    Full Text Available The human inferior frontal cortex (IFC is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear.We conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval and during the performance of a stop-signal task (requiring response generation and inhibition in comparison to a not-stop task (requiring response generation but not inhibition. We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control.Our findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits.

  20. Behavioral inhibition in rhesus monkeys (Macaca mulatta is related to the airways response, but not immune measures, commonly associated with asthma.

    Directory of Open Access Journals (Sweden)

    Katie Chun

    Full Text Available Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between behavioral inhibition and airway hyperresponsiveness, and whether hormonal and immune measures often associated with asthma were associated with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49 yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals, we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-γ in response to stimulation, as well as peripheral blood cell percentages, cortisol levels, and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+. Airway reactivity was assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was performed and the proportion of immune cells was determined. Behaviorally inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine challenge (p=0.031, confirming our earlier retrospective result. Airway hyperresponsiveness was also associated with lower lymphocyte percentages in lavage fluid and marginally lower plasma cortisol concentrations. However, none of the tested measures was significantly related to both behavioral inhibition and airway hyperresponsiveness, and so could not mediate their relationship. Airway hyperresponsiveness is common to atopic and non-atopic asthma and behavioral inhibition has been related to altered autonomic activity in other studies. Our results suggest that behavioral inhibition might index an autonomically mediated reactive airway phenotype, and that a variety of stimuli (including inflammation within

  1. Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A

    International Nuclear Information System (INIS)

    Cencic, R; Robert, F; Galicia-Vázquez, G; Malina, A; Ravindar, K; Somaiah, R; Pierre, P; Tanaka, J; Deslongchamps, P; Pelletier, J

    2013-01-01

    Translation is regulated predominantly at the initiation phase by several signal transduction pathways that are often usurped in human cancers, including the PI3K/Akt/mTOR axis. mTOR exerts unique administration over translation by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex responsible for recruiting 40S ribosomes (and associated factors) to mRNA 5′ cap structures. Hence, there is much interest in targeted therapies that block eIF4F activity to assess the consequences on tumor cell growth and chemotherapy response. We report here that hippuristanol (Hipp), a translation initiation inhibitor that selectively inhibits the eIF4F RNA helicase subunit, eIF4A, resensitizes Eμ-Myc lymphomas to DNA damaging agents, including those that overexpress eIF4E—a modifier of rapamycin responsiveness. As Mcl-1 levels are significantly affected by Hipp, combining its use with the Bcl-2 family inhibitor, ABT-737, leads to a potent synergistic response in triggering cell death in mouse and human lymphoma and leukemia cells. Suppression of eIF4AI using RNA interference also synergized with ABT-737 in murine lymphomas, highlighting eIF4AI as a therapeutic target for modulating tumor cell response to chemotherapy

  2. Interactive effects of music and prefrontal cortex stimulation in modulating response inhibition.

    Science.gov (United States)

    Mansouri, Farshad Alizadeh; Acevedo, Nicola; Illipparampil, Rosin; Fehring, Daniel J; Fitzgerald, Paul B; Jaberzadeh, Shapour

    2017-12-22

    Influential hypotheses propose that alterations in emotional state influence decision processes and executive control of behavior. Both music and transcranial direct current stimulation (tDCS) of prefrontal cortex affect emotional state, however interactive effects of music and tDCS on executive functions remain unknown. Learning to inhibit inappropriate responses is an important aspect of executive control which is guided by assessing the decision outcomes such as errors. We found that high-tempo music, but not low-tempo music or low-level noise, significantly influenced learning and implementation of inhibitory control. In addition, a brief period of tDCS over prefrontal cortex specifically interacted with high-tempo music and altered its effects on executive functions. Measuring event-related autonomic and arousal response of participants indicated that exposure to task demands and practice led to a decline in arousal response to the decision outcome and high-tempo music enhanced such practice-related processes. However, tDCS specifically moderated the high-tempo music effect on the arousal response to errors and concomitantly restored learning and improvement in executive functions. Here, we show that tDCS and music interactively influence the learning and implementation of inhibitory control. Our findings indicate that alterations in the arousal-emotional response to the decision outcome might underlie these interactive effects.

  3. Facility Response Plan (FRP) Points, Region 9, 2014, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — A Facility Response Plan (FRP) demonstrates a facility's preparedness to respond to a worst case oil discharge. Under the Clean Water Act, as amended by the Oil...

  4. Facility Response Plan (FRP) Points, Region 9, 2013, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — A Facility Response Plan (FRP) demonstrates a facility's preparedness to respond to a worst case oil discharge. Under the Clean Water Act, as amended by the Oil...

  5. Facility Response Plan (FRP) Points, Region 9, 2012, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — A Facility Response Plan (FRP) demonstrates a facility's preparedness to respond to a worst case oil discharge. Under the Clean Water Act, as amended by the Oil...

  6. Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bao-Qin; Gao, Yan-Yan; Niu, Xiao-Fang [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China); Xie, Ji-Sheng [Youjiang Medical College for Nationalities, Guangxi 533000 (China); Meng, Xin; Guan, Yifu [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China); Wang, Hua-Qin, E-mail: wanghq_doctor@hotmail.com [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China)

    2010-01-01

    Resveratrol (RES), a natural plant polyphenol, is an effective inducer of cell cycle arrest and apoptosis in a variety of carcinoma cell types. In addition, RES has been reported to inhibit tumorigenesis in several animal models suggesting that it functions as a chemopreventive and anti-tumor agent in vivo. The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the design of new chemotherapeutic agents. However, the mechanisms by which RES mediates its effects are not yet fully understood. In this study, we showed that RES caused cell cycle arrest and proliferation inhibition via induction of unfolded protein response (UPR) in human leukemia K562 cell line. Treatment of K562 cells with RES induced a number of signature UPR markers, including transcriptional induction of GRP78 and CHOP, phosphorylation of eukaryotic initiation factor 2{alpha} (eIF2{alpha}), ER stress-specific XBP-1 splicing, suggesting the induction of UPR by RES. RES inhibited proliferation of K562 in a concentration-dependent manner. Flow cytometric analyses revealed that K562 cells were arrested in G1 phase upon RES treatment. Salubrinal, an eIF2{alpha} inhibitor, or overexpression of dominant negative mutants of PERK or eIF2{alpha}, effectively restored RES-induced cell cycle arrest, underscoring the important role of PERK/eIF2{alpha} branch of UPR in RES-induced inhibition of cell proliferation.

  7. Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation

    International Nuclear Information System (INIS)

    Liu, Bao-Qin; Gao, Yan-Yan; Niu, Xiao-Fang; Xie, Ji-Sheng; Meng, Xin; Guan, Yifu; Wang, Hua-Qin

    2010-01-01

    Resveratrol (RES), a natural plant polyphenol, is an effective inducer of cell cycle arrest and apoptosis in a variety of carcinoma cell types. In addition, RES has been reported to inhibit tumorigenesis in several animal models suggesting that it functions as a chemopreventive and anti-tumor agent in vivo. The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the design of new chemotherapeutic agents. However, the mechanisms by which RES mediates its effects are not yet fully understood. In this study, we showed that RES caused cell cycle arrest and proliferation inhibition via induction of unfolded protein response (UPR) in human leukemia K562 cell line. Treatment of K562 cells with RES induced a number of signature UPR markers, including transcriptional induction of GRP78 and CHOP, phosphorylation of eukaryotic initiation factor 2α (eIF2α), ER stress-specific XBP-1 splicing, suggesting the induction of UPR by RES. RES inhibited proliferation of K562 in a concentration-dependent manner. Flow cytometric analyses revealed that K562 cells were arrested in G1 phase upon RES treatment. Salubrinal, an eIF2α inhibitor, or overexpression of dominant negative mutants of PERK or eIF2α, effectively restored RES-induced cell cycle arrest, underscoring the important role of PERK/eIF2α branch of UPR in RES-induced inhibition of cell proliferation.

  8. Caffeoyl glucosides from Nandina domestica inhibit LPS-induced endothelial inflammatory responses.

    Science.gov (United States)

    Kulkarni, Roshan R; Lee, Wonhwa; Jang, Tae Su; Lee, JungIn; Kwak, Soyoung; Park, Mi Seon; Lee, Hyun-Shik; Bae, Jong-Sup; Na, MinKyun

    2015-11-15

    Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, a new caffeoyl glucoside (1) and two known caffeoylated compounds (2 and 3) were isolated from the fruits of Nandina domestica Thunb. (Berberidaceae). The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses. At 20 μM, 1 and 2 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer in a dose-dependent manner suggesting that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Inhibition of the SOS response of Escherichia coli by the Ada protein

    International Nuclear Information System (INIS)

    Vericat, J.A.; Guerrero, R.; Barbe, J.

    1988-01-01

    Induction of the adaptive response by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) caused a decrease in the UV-mediated expression of both recA and sfiA genes but not of the umuDC gene. On the other hand, the adaptive response did not affect the temperature-promoted induction of SOS response in a RecA441 mutant. The inhibitory effect on the UV-triggered expression of the recA and sfiA genes was not dependent on either the alkA gene or the basal level of RecA protein, but rather required the ada gene. Furthermore, an increase in the level of the Ada protein, caused by the runaway plasmid pYN3059 in which the ada gene is regulated by the lac promoter, inhibited UV-mediated recA gene expression even in cells to which the MNNG-adaptive treatment had not been applied. This inhibitory effect of the adaptive pretreatment was not observed either in RecBC- strains or in RecBC mutants lacking exonuclease V-related nuclease activity. However, RecF- mutants showed an adaptive response-mediated decrease in UV-promoted induction of the recA gene

  10. Thiol dependent NF-κB suppression and inhibition of T-cell mediated adaptive immune responses by a naturally occurring steroidal lactone Withaferin A

    Energy Technology Data Exchange (ETDEWEB)

    Gambhir, Lokesh; Checker, Rahul; Sharma, Deepak; Thoh, M. [Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai (India); Patil, Anand [Advanced Centre for Treatment Research and Education in Cancer, Kharghar, Navi Mumbai (India); Degani, M. [Institute of Chemical Technology, Matunga, Mumbai (India); Gota, Vikram [Advanced Centre for Treatment Research and Education in Cancer, Kharghar, Navi Mumbai (India); Sandur, Santosh K., E-mail: sskumar@barc.gov.in [Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai (India)

    2015-12-01

    Withaferin A (WA), a steroidal lactone isolated from ayurvedic medicinal plant Withania somnifera, was shown to inhibit tumor growth by inducing oxidative stress and suppressing NF-κB pathway. However, its effect on T-cell mediated adaptive immune responses and the underlying mechanism has not been investigated. Since both T-cell responses and NF-κB pathway are known to be redox sensitive, the present study was undertaken to elucidate the effect of WA on adaptive immune responses in vitro and in vivo. WA inhibited mitogen induced T-cell and B-cell proliferation in vitro without inducing any cell death. It inhibited upregulation of T-cell (CD25, CD69, CD71 and CD54) and B-cell (CD80, CD86 and MHC-II) activation markers and secretion of Th1 and Th2 cytokines. WA induced oxidative stress by increasing the basal ROS levels and the immunosuppressive effects of WA were abrogated only by thiol anti-oxidants. The redox modulatory effects of WA in T-cells were attributed to its ability to directly interact with free thiols. WA inhibited NF-κB nuclear translocation in lymphocytes and prevented the direct binding of nuclear NF-κB to its consensus sequence. MALDI-TOF analysis using a synthetic NF-κB-p50 peptide containing Cys-62 residue suggested that WA can modify the cysteine residue of NF-κB. The pharmacokinetic studies for WA were also carried out and in vivo efficacy of WA was studied using mouse model of Graft-versus-host disease. In conclusion, WA is a potent inhibitor of T-cell responses and acts via a novel thiol dependent mechanism and inhibition of NF-κB pathway. - Highlights:: • Withaferin A (WA) inhibited T-cell and B-cell mediated immune responses. • WA increased basal ROS levels in lymphocytes. • WA directly interacted with GSH as studied using spectrophotometry and HPLC. • WA inhibited NF-κB nuclear translocation and binding of nuclear NF-κB to DNA. • WA inhibited induction of the graft-versus-host disease in mice.

  11. Response inhibition deficits in children with Fetal Alcohol Spectrum Disorder: Relationship between diffusion tensor imaging of the corpus callosum and eye movement control

    Directory of Open Access Journals (Sweden)

    Angelina Paolozza

    2014-01-01

    Full Text Available Response inhibition is the ability to suppress irrelevant impulses to enable goal-directed behavior. The underlying neural mechanisms of inhibition deficits are not clearly understood, but may be related to white matter connectivity, which can be assessed using diffusion tensor imaging (DTI. The goal of this study was to investigate the relationship between response inhibition during the performance of saccadic eye movement tasks and DTI measures of the corpus callosum in children with or without Fetal Alcohol Spectrum Disorder (FASD. Participants included 43 children with an FASD diagnosis (12.3 ± 3.1 years old and 35 typically developing children (12.5 ± 3.0 years old both aged 7–18, assessed at three sites across Canada. Response inhibition was measured by direction errors in an antisaccade task and timing errors in a delayed memory-guided saccade task. Manual deterministic tractography was used to delineate six regions of the corpus callosum and calculate fractional anisotropy (FA, mean diffusivity (MD, parallel diffusivity, and perpendicular diffusivity. Group differences in saccade measures were assessed using t-tests, followed by partial correlations between eye movement inhibition scores and corpus callosum FA and MD, controlling for age. Children with FASD made more saccade direction errors and more timing errors, which indicates a deficit in response inhibition. The only group difference in DTI metrics was significantly higher MD of the splenium in FASD compared to controls. Notably, direction errors in the antisaccade task were correlated negatively to FA and positively to MD of the splenium in the control, but not the FASD group, which suggests that alterations in connectivity between the two hemispheres of the brain may contribute to inhibition deficits in children with FASD.

  12. Planning guidance for emergency response to a hypothetical nuclear attack on Riyadh, Saudi Arabia

    Science.gov (United States)

    Shubayr, Nasser Ali M.

    The threat of nuclear attack will remain imminent in an ever-advancing society. Saudi Arabia is not immune to this threat. This dissertation establishes planning guidance for response to a nuclear attack on Riyadh, the capital of Saudi Arabia, based on a hypothetical scenario of a nuclear detonation. A case scenario of a one-megaton thermonuclear bomb detonated at ground level over Riyadh is used to support the thesis. Previous nuclear tests and the Hiroshima and Nagasaki bombings have been used to present possible effects on Riyadh. US planning guidance and lessons learned from the Chernobyl and Fukushima nuclear plants accidents have been used to develop the emergency response guidance. The planning guidance outlines a rapid response to the nuclear detonation. Four damage zones have been identified; severe damage zone, moderate damage zone, light damage zone and dangerous fallout zone. Actions that are recommended, and those that should be avoided, have been determined for each zone. Shelter/ evacuation evaluation for blast-affected and fallout-affected areas is the basis for the recommendation that shelter in place is the best decision for the first hours to days after the attack. Guidelines for medical care response and population monitoring and decontamination are included to reduce the early and long-term effects of the attack. Recommendations to the Saudi Arabian authorities have been made to facilitate suitable preparedness and response for such an event.

  13. Transformation Planning of Ecotourism Systems to Invigorate Responsible Tourism

    OpenAIRE

    Yun Eui Choi; Minsun Doh; Samuel Park; Jinhyung Chon

    2017-01-01

    The purpose of this study is to introduce transformation plans that can stimulate responsible ecotourism by using systems thinking to solve ecotourism problems in Korea. Systems thinking is a research method used to understand the operating mechanisms of the variables that influence an entire system, in order to identify its problems. The four types of ecotourism systems are classified as follows: low-infrastructure and resident-initiated, high-infrastructure and resident-initiated, high-infr...

  14. Stakeholder insights on the planning and development of an independent benchmark standard for responsible food marketing.

    Science.gov (United States)

    Cairns, Georgina; Macdonald, Laura

    2016-06-01

    A mixed methods qualitative survey investigated stakeholder responses to the proposal to develop an independently defined, audited and certifiable set of benchmark standards for responsible food marketing. Its purpose was to inform the policy planning and development process. A majority of respondents were supportive of the proposal. A majority also viewed the engagement and collaboration of a broad base of stakeholders in its planning and development as potentially beneficial. Positive responses were associated with views that policy controls can and should be extended to include all form of marketing, that obesity and non-communicable diseases prevention and control was a shared responsibility and an urgent policy priority and prior experience of independent standardisation as a policy lever for good practice. Strong policy leadership, demonstrable utilisation of the evidence base in its development and deployment and a conceptually clear communications plan were identified as priority targets for future policy planning. Future research priorities include generating more evidence on the feasibility of developing an effective community of practice and theory of change, the strengths and limitations of these and developing an evidence-based step-wise communications strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Altered neural connectivity during response inhibition in adolescents with attention-deficit/hyperactivity disorder and their unaffected siblings

    NARCIS (Netherlands)

    van Rooij, Daan; Hartman, Catharina A.; Mennes, Maarten; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Heslenfeld, Dirk; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

    2015-01-01

    Introduction: Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates that altered functional and structural neural connectivity are part of the neurobiological basis of ADHD. Here, we investigated if

  16. Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

    International Nuclear Information System (INIS)

    St Denny, I.H.; Glinka, K.G.; Nemecek, G.M.; Stuetz, A.

    1987-01-01

    Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5μM T in fibroblast incubation media was associated with increased [ 3 H]thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6μM reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 μM. Neither the uptake of [ 3 H]thymidine nor the specific binding of 125 I-PDGF to fibroblast receptors was significantly affected by 10 μM T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism

  17. Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

    Energy Technology Data Exchange (ETDEWEB)

    St. Denny, I.H.; Glinka, K.G.; Nemecek, G.M. (Sandoz Research Institute, East Hanover, NJ (USA)); Stuetz, A. (Sandoz Forschungsinstitut, Vienna (Austria))

    1987-05-01

    Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5{mu}M T in fibroblast incubation media was associated with increased ({sup 3}H)thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6{mu}M reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 {mu}M. Neither the uptake of ({sup 3}H)thymidine nor the specific binding of {sup 125}I-PDGF to fibroblast receptors was significantly affected by 10 {mu}M T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism.

  18. The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response.

    Directory of Open Access Journals (Sweden)

    Jan Karlseder

    2004-08-01

    Full Text Available The telomeric protein TRF2 is required to prevent mammalian telomeres from activating DNA damage checkpoints. Here we show that overexpression of TRF2 affects the response of the ATM kinase to DNA damage. Overexpression of TRF2 abrogated the cell cycle arrest after ionizing radiation and diminished several other readouts of the DNA damage response, including phosphorylation of Nbs1, induction of p53, and upregulation of p53 targets. TRF2 inhibited autophosphorylation of ATM on S1981, an early step in the activation of this kinase. A region of ATM containing S1981 was found to directly interact with TRF2 in vitro, and ATM immunoprecipitates contained TRF2. We propose that TRF2 has the ability to inhibit ATM activation at telomeres. Because TRF2 is abundant at chromosome ends but not elsewhere in the nucleus, this mechanism of checkpoint control could specifically block a DNA damage response at telomeres without affecting the surveillance of chromosome internal damage.

  19. Less approach, more avoidance: Response inhibition has motivational consequences for sexual stimuli that reflect changes in affective value not a lingering global brake on behavior.

    Science.gov (United States)

    Driscoll, Rachel L; de Launay, Keelia Quinn; Fenske, Mark J

    2018-02-01

    Response inhibition negatively impacts subsequent hedonic evaluations of motivationally relevant stimuli and reduces the behavioral incentive to seek and obtain such items. Here we expand the investigation of the motivational consequences of inhibition by presenting sexually appealing and nonappealing images in a go/no-go task and a subsequent image-viewing task. Each initially obscured image in the viewing task could either be made more visible or less visible by repeatedly pressing different keys. Fewer key presses were made to obtain better views of preferred-sex images when such images had previously been inhibited as no-go items than when previously encountered as noninhibited go items. This finding replicates prior results and is consistent with the possibility that motor-response suppression has lingering effects that include global reductions in all behavioral expression. However, for nonpreferred images, prior inhibition resulted in more key presses to obscure their visibility than when such images had not been inhibited. This novel finding suggests that the motivational consequences of response inhibition are not due to a global brake on action but are instead linked to negative changes in stimulus value that induce corresponding increases in avoidance and decreases in approach.

  20. Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup.

    Science.gov (United States)

    2000-04-21

    The U.S. national civilian vulnerability to the deliberate use of biological and chemical agents has been highlighted by recognition of substantial biological weapons development programs and arsenals in foreign countries, attempts to acquire or possess biological agents by militants, and high-profile terrorist attacks. Evaluation of this vulnerability has focused on the role public health will have detecting and managing the probable covert biological terrorist incident with the realization that the U.S. local, state, and federal infrastructure is already strained as a result of other important public health problems. In partnership with representatives for local and state health departments, other federal agencies, and medical and public health professional associations, CDC has developed a strategic plan to address the deliberate dissemination of biological or chemical agents. The plan contains recommendations to reduce U.S. vulnerability to biological and chemical terrorism--preparedness planning, detection and surveillance, laboratory analysis, emergency response, and communication systems. Training and research are integral components for achieving these recommendations. Success of the plan hinges on strengthening the relationships between medical and public health professionals and on building new partnerships with emergency management, the military, and law enforcement professionals.

  1. NF-κB-Activating Complex Engaged in Response to EGFR Oncogene Inhibition Drives Tumor Cell Survival and Residual Disease in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Collin M. Blakely

    2015-04-01

    Full Text Available Although oncogene-targeted therapy often elicits profound initial tumor responses in patients, responses are generally incomplete because some tumor cells survive initial therapy as residual disease that enables eventual acquired resistance. The mechanisms underlying tumor cell adaptation and survival during initial therapy are incompletely understood. Here, through the study of EGFR mutant lung adenocarcinoma, we show that NF-κB signaling is rapidly engaged upon initial EGFR inhibitor treatment to promote tumor cell survival and residual disease. EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NF-κB-mediated transcriptional survival program. The direct NF-κB inhibitor PBS-1086 suppressed this adaptive survival program and increased the magnitude and duration of initial EGFR inhibitor response in multiple NSCLC models, including a patient-derived xenograft. These findings unveil NF-κB activation as a critical adaptive survival mechanism engaged by EGFR oncogene inhibition and provide rationale for EGFR and NF-κB co-inhibition to eliminate residual disease and enhance patient responses.

  2. Lessons learned from the second Federal Radiology Emergency Response Plan Field Exercise (FFE-2)

    International Nuclear Information System (INIS)

    Adler, M.V.; Gant, K.S.; Weiss, B.H.; Wolff, W.F.; Adler, V.

    1988-01-01

    The FFE-2, held in 1987 at the Zion Nuclear Power Station, provided a large-scale, multiagency, field test of the Federal Radiological Emergency Response Plan (FRERP). The FRERP provided workable guidance for coordinating the federal response efforts and effectively supplementing the states' resources. Needs for more training for responders and clarification in portions of the response were identified

  3. Application of Group-Level Item Response Models in the Evaluation of Consumer Reports about Health Plan Quality

    Science.gov (United States)

    Reise, Steven P.; Meijer, Rob R.; Ainsworth, Andrew T.; Morales, Leo S.; Hays, Ron D.

    2006-01-01

    Group-level parametric and non-parametric item response theory models were applied to the Consumer Assessment of Healthcare Providers and Systems (CAHPS[R]) 2.0 core items in a sample of 35,572 Medicaid recipients nested within 131 health plans. Results indicated that CAHPS responses are dominated by within health plan variation, and only weakly…

  4. The response to a worst-case scenario - the national emergency plan for nuclear accidents

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham D, John [Radiological Protection Inst. of Ireland (Ireland)

    1996-10-01

    The Chernobyl accident in 1986 highlighted many deficiencies in the preparedness of countries to deal with a major accident. It demonstrated how vulnerable countries are to transboundary contamination. Ireland had no emergency plan at the time of the accident and only minimal facilities with which to assess the consequences of the accident. Nonetheless, the then Nuclear Energy Board with the assistance of Government Departments and the Civil Defence organisation reacted quickly to assess the situation despite the complete lack of information about the accident from the then USSR. Even countries with advanced nuclear technologies faced similar difficulties. It was quickly recognised by Government that the national laboratory facilities were totally inadequate. The Nuclear Energy Board was provided with additional resources to assist it to cope in the short term with the very large demand for monitoring. In the longer term a new national radiation laboratory was provided and the Board was formally replaced by the Radiological Protection Institute of Ireland. It was given statutory responsibility to monitor radiation levels, to advise measures to be taken for the protection of the public and to provide information for the public. An emergency plan based on the Chernobyl experience was drafted in 1987, amended and published in 1992. Certain features of this plan were implemented from 1987 onwards, notably the classification of responsibilities and the installation of a national continuous radiation monitoring system. The paper outlines the responsibilities of those who could be involved in a response to a nuclear incident, the procedures used to evaluate its consequences and the provision of information for the public. The plan provides an integrated management system which has sufficient flexibility to enable a rapid response to be made to a major or minor crisis, either foreseen or unforeseen and whatever its cause.

  5. Scrupulosity and contamination OCD are not associated with deficits in response inhibition.

    Science.gov (United States)

    Rasmussen, Jessica; Siev, Jedidiah; Abramovitch, Amitai; Wilhelm, Sabine

    2016-03-01

    Prior research has indicated a number of neuropsychological deficits in patients with OCD consistent with the cortico-striato-thalamo-cortical model of the disorder. Response inhibition (RI), defined as the inability to inhibit a prepotent response, has been identified as a possible candidate endophenotype for OCD. However, the results from previous studies of RI in OCD patients have been mixed, suggesting the possibility that some OCD dimensions may be associated with deficits in RI while others may not. The present study aimed to examine RI using a Go/No-Go (GNG) task in two OCD symptom dimensions, one of which, scrupulosity, has never been subject to neuropsychological investigation. A total of 63 individuals, consisting of scrupulous OCD (n = 26), contamination OCD (n = 18) and non-psychiatric controls (n = 19) completed study measures. Controlling for depression symptoms, no significant performance differences were found between the groups on the GNG test, indicating no deficits in RI among contamination or scrupulous OCD. Results are consistent with several prior studies of RI in OCD that found no differences as compared to non-psychiatric controls, especially on GNG tests, and with more recent suggestions that RI may not constitute a clinical significant impaired domain in OCD. Limitations included a primarily highly educated and Caucasian sample. Additional conclusions include careful consideration of the RI measures selected for future studies, as well as the need for further investigation into the neuropsychological and neurobiological nature of scrupulous OCD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Impulse control disorder and response-inhibition alterations in Parkinson's disease. A rare case of totally absent functionality of the medial-prefrontal cortex and review of literature.

    Science.gov (United States)

    Palermo, Sara; Morese, Rosalba; Zibetti, Maurizio; Dematteis, Francesca; Sirgiovanni, Stefano; Stanziano, Mario; Valentini, Maria Consuelo; Lopiano, Leonardo

    2017-11-01

    This report illustrates a Parkinson's disease (PD) patient with impulse-control disorder (ICD) and selective impairment in response-inhibition abilities as revealed by the performance in a functional magnetic resonance imaging (fMRI) anterior cingulate cortex - sensitive go-nogo task. In line with hypothesis on the role of response-inhibition disabilities in the arising of impulsivity in PD, the patient completely failed the go-nogo task. Moreover, fMRI acquisition revealed absent task-sensitive activity in the anterior cingulate cortex, medial prefrontal, and orbitofrontal cortices for the contrast nogo versus go, which signifying that a hypo-function of this network could be associated with ICD. A fronto-striatal and cingulo-frontal dysfunction may reflect impairment in metacognitive-executive abilities (such as response-inhibition, action monitoring, and error awareness) and promote compulsive repetition of behavior. Response-inhibition tasks may be useful in PD post-diagnostic phase, to better identify individuals at risk of developing ICD with dopaminergic medication.

  7. Anthelminthic drug niclosamide sensitizes the responsiveness of cervical cancer cells to paclitaxel via oxidative stress-mediated mTOR inhibition

    International Nuclear Information System (INIS)

    Chen, Liping; Wang, Li; Shen, Haibin; Lin, Hui; Li, Dan

    2017-01-01

    Drug repurposing represents an alternative therapeutic strategy to cancer treatment. The potent anti-cancer activities of a FDA-approved anthelminthic drug niclosamide have been demonstrated in various cancers. However, whether niclosamide is active against cervical cancer is unknown. In this study, we investigated the effects of niclosamide alone and its combination with paclitaxel in cervical cancer in vitro and in vivo. We found that niclosamide significantly inhibited proliferation and induced apoptosis of a panel of cervical cancer cell lines, regardless of their cellular origin and genetic pattern. Niclosamide also inhibited tumor growth in cervical cancer xenograft mouse model. Importantly, niclosamide significantly enhanced the responsiveness of cervical cancer cell to paclitaxel. We further found that niclosamide induced mitochondrial dysfunctions via inhibiting mitochondrial respiration, complex I activity and ATP generation, which led to oxidative stress. ROS scavenge agent N-acetyl-L-cysteine (NAC) completely reversed the effects of niclosamide in increasing cellular ROS, inhibiting proliferation and inducing apoptosis, suggesting that oxidative stress induction is the mechanism of action of niclosamide in cervical cancer cells. In addition, niclosamide significantly inhibited mammalian target of rapamycin (mTOR) signaling pathway in cervical cancer cells and its inhibitory effect on mTOR is modulated by oxidative stress. Our work suggests that niclosamide is a useful addition to the treatment armamentarium for cervical cancer and induction of oxidative stress may be a potential therapeutic strategy in cervical cancer. - Highlights: • Niclosamide is active against cervical cancer cells in vitro and in vivo. • Niclosamide sensitizes cervical cancer cell response to paclitaxel. • Niclosamide induces mitochondrial dysfunction and oxidative damage. • Niclosamide inhibits mTOR signaling in an oxidative stress-dependent manner.

  8. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response.

    Science.gov (United States)

    Malakhova, Oxana A; Zhang, Dong-Er

    2008-04-04

    Interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. The interferon-inducible ubiquitin-like protein ISG15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. In addition, protein ubiquitination plays a regulatory role in the immune system. Many viruses modulate the ubiquitin (Ub) pathway to alter cellular signaling and the antiviral response. Ubiquitination of retroviral group-specific antigen precursors and matrix proteins of the Ebola, vesicular stomatitis, and rabies viruses by Nedd4 family HECT domain E3 ligases is an important step in facilitating viral release. We found that Nedd4 is negatively regulated by ISG15. Free ISG15 specifically bound to Nedd4 and blocked its interaction with Ub-E2 molecules, thus preventing further Ub transfer from E2 to E3. Furthermore, overexpression of ISG15 diminished the ability of Nedd4 to ubiquitinate viral matrix proteins and led to a decrease in the release of Ebola VP40 virus-like particles from the cells. These results point to a mechanistically novel function of ISG15 in the enhancement of the innate anti-viral response through specific inhibition of Nedd4 Ub-E3 activity. To our knowledge, this is the first example of a Ub-like protein with the ability to interfere with Ub-E2 and E3 interaction to inhibit protein ubiquitination.

  9. Public comments and responses to the 1989 Hanford cleanup five-year plan

    International Nuclear Information System (INIS)

    1991-06-01

    In April 1990 the US Department of Energy (DOE) issued a site- specific Five-Year Plan (DOE-RL 1989a) on Hanford's cleanup for public review and comment. The plan guides Hanford in carrying out DOE's national plan for environmental restoration and waste management. During the 90-day public comment period, DOE held nine public meetings to answer questions and gather comments on the plan. This report is in three main sections. The first presents consolidated public comments and responses. These were compiled from both verbal comments from public meetings and written comments. The second section contains comments not responded to in this plan. Those comments were outside this plan's scope, related to how we gathered public comments, or intended for and directed to DOE-Headquarters. In the appendixes are the written comment letters we received and a short glossary and list of special terms we use. The source of comments is shown in parentheses after the comment. The individual who made the comment, the city of the public meeting, or the organization name is generally used. When several sources gave the same comment, a source was not listed. 26 refs

  10. Gliclazide directly inhibits arginine-induced glucagon release

    DEFF Research Database (Denmark)

    Cejvan, Kenan; Coy, David H; Holst, Jens Juul

    2002-01-01

    Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

  11. Inhibition of EGF processing in responsive and nonresponsive human fibroblasts

    International Nuclear Information System (INIS)

    Schaudies, R.P.; Wray, H.L.

    1988-01-01

    We have examined the proteolytic processing of radiolabeled epidermal growth factor (EGF) in EGF growth-responsive human foreskin fibroblasts (HFF) versus EGF nonresponsive human fetal lung fibroblasts (HFL). Previous studies have shown that both cell lines demonstrate similar binding affinities and numbers of binding sites, as well as similar rates of internalization and degradation of the bound, radiolabeled hormone. We have used nondenaturing electrophoresis to compare how these two cell lines process EGF at its carboxy terminus. EGF lacking either one [des-(53)-EGF] or six [des (48-53)-EGF] carboxy terminal amino acids could be distinguished by this method. Chloroquine or leupeptin were added to the incubation system in an attempt to accentuate potential differences in hormonal processing between the responsive and nonresponsive cell lines. In the absence of inhibitors, the responsive and nonresponsive cells generated similar distributions of processed forms of EGF after 30-minutes incubation. However, after 4-hours incubation in the constant presence of 125I-EGF, the electrophoretic profiles of extracted hormone were substantially different. The radiolabel within the responsive cells, as well as that released from them, migrated predominantly at the dye front, indicating complete degradation of EGF. In contrast, the majority of the radiolabel within the nonresponsive cells migrated as partially processed forms of hormone, while the released radiolabel migrated at the dye front. Addition of chloroquine to either cell line inhibited processing of EGF beyond removal of the carboxyl terminal arginine residue. Both intact 125I-EGF, and 125I-EGF lacking the carboxyl terminal arginine were released from chloroquine-treated cells in a ratio equal to that present in the intact cells

  12. Buffering social influence: neural correlates of response inhibition predict driving safety in the presence of a peer.

    Science.gov (United States)

    Cascio, Christopher N; Carp, Joshua; O'Donnell, Matthew Brook; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G; Falk, Emily B

    2015-01-01

    Adolescence is a period characterized by increased sensitivity to social cues, as well as increased risk-taking in the presence of peers. For example, automobile crashes are the leading cause of death for adolescents, and driving with peers increases the risk of a fatal crash. Growing evidence points to an interaction between neural systems implicated in cognitive control and social and emotional context in predicting adolescent risk. We tested such a relationship in recently licensed teen drivers. Participants completed an fMRI session in which neural activity was measured during a response inhibition task, followed by a separate driving simulator session 1 week later. Participants drove alone and with a peer who was randomly assigned to express risk-promoting or risk-averse social norms. The experimentally manipulated social context during the simulated drive moderated the relationship between individual differences in neural activity in the hypothesized cognitive control network (right inferior frontal gyrus, BG) and risk-taking in the driving context a week later. Increased activity in the response inhibition network was not associated with risk-taking in the presence of a risky peer but was significantly predictive of safer driving in the presence of a cautious peer, above and beyond self-reported susceptibility to peer pressure. Individual differences in recruitment of the response inhibition network may allow those with stronger inhibitory control to override risky tendencies when in the presence of cautious peers. This relationship between social context and individual differences in brain function expands our understanding of neural systems involved in top-down cognitive control during adolescent development.

  13. Interagency Communication and Collaboration on School Crisis Response Planning and Management

    Science.gov (United States)

    Skavdahl, Britta M.

    2010-01-01

    Purpose. The purpose of this study was to determine what research-based and federally recommended practices in the area of school crisis response planning and management were being implemented in K-8 school districts in Northern California, as well as the degree with which the recommended practices were being implemented. Finally, the study…

  14. Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

    Directory of Open Access Journals (Sweden)

    Xuan Luo

    2018-02-01

    Full Text Available Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2. Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

  15. Planning and preparing for emergency response to transport accidents involving radioactive material. Safety guide

    International Nuclear Information System (INIS)

    2005-01-01

    The objective of this Safety Guide is to provide guidance to the public authorities and others (including consignors, carriers and emergency response authorities) who are responsible for developing and establishing emergency arrangements for dealing effectively and safely with transport accidents involving radioactive material. It may assist those concerned with establishing the capability to respond to such transport emergencies. It provides guidance for those Member States whose involvement with radioactive material is just beginning. It also provides guidance for those Member States that have already developed their radioactive material industries and the attendant emergency plans but that may need to review and improve these plans

  16. Application of Real-Time Automated Traffic Incident Response Plan Management System: A Web Structure for the Regional Highway Network in China

    Directory of Open Access Journals (Sweden)

    Yongfeng Ma

    2014-01-01

    Full Text Available Traffic incidents, caused by various factors, may lead to heavy traffic delay and be harmful to traffic capacity of downstream sections. Traffic incident management (TIM systems have been developed widely to respond to traffic incidents intelligently and reduce the losses. Traffic incident response plans, as an important component of TIM, can effectively guide responders as to what and how to do in traffic incidents. In the paper, a real-time automated traffic incident response plan management system was developed, which could generate and manage traffic incident response plans timely and automatically. A web application structure and a physical structure were designed to implement and show these functions. A standard framework of data storage was also developed to save information about traffic incidents and generated response plans. Furthermore, a conformation survey and case-based reasoning (CBR were introduced to identify traffic incident and generate traffic incident response plans automatically, respectively. Twenty-three traffic crash-related incidents were selected and three indicators were used to measure the system performance. Results showed that 20 of 23 cases could be retrieved effectively and accurately. The system is practicable to generate traffic incident response plans and has been implemented in China.

  17. Assessment of emergency response planning and implementation in the aftermath of major natural disasters and technological accidents

    International Nuclear Information System (INIS)

    Milligan, Patricia A.; Jones, Joseph; Walton, F.; Smith, J.D.

    2008-01-01

    Emergency planning around nuclear power plants represents some of the most mature and well developed emergency planning in the United States. Since the implementation of NUREG-0654 / FEMA-REP-1, Rev. 1, A Criteria for Preparation and Evaluation of Radiological Emergency Response Plans and Preparedness in Support of Nuclear Power Plants (NRC, 1980a) the licensees, local, and State agencies have developed detailed Radiological Emergency Response Programs. An important component of these plans is the evacuation of the population in the event of a general emergency condition at the plant. In January 2005, the U.S. Nuclear Regulatory Commission (NRC) published the landmark report, 'Identification and Analysis of Factors Affecting Emergency Evacuations' (NUREG/CR 6864/), which represented the most comprehensive investigation of public evacuations in the United States in more than 15 years. Since the completion of this research, several high profile evacuations have occurred, including Hurricane Katrina in New Orleans, Hurricane Rita in Houston, as well as major wildfires across the western U.S. The NRC commissioned an update to its 2005 evacuation case study publication to evaluate the evacuation experience of the selected communities (e.g., timeliness, related injuries, hazard avoidance); the level of preplanning that was in place for the affected areas and extent that the pre planned requirements were implemented during the emergency response; the critical factors contributing to the efficiency of or impediments to the evacuations (e.g., training, drills, preparedness, experience, resources, facilities, and organizational structure); and additional factors that may have contributed to less than satisfactory public response (i.e., availability of personal transportation, use of public transportation, lack of availability of shelters, etc.). The comprehensive report will be published in fall of 2008 as NUREG/CR-6981, Assessment of Emergency Response Planning and

  18. Facility Response Plan (FRP) Inspected Points, Region 9, 2014, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — A Facility Response Plan (FRP) demonstrates a facility's preparedness to respond to a worst case oil discharge. Under the Clean Water Act, as amended by the Oil...

  19. Particular intervention plan of the Civaux Nuclear Power Plant. Public version. Special provision of the organisation plan for civil protection response

    International Nuclear Information System (INIS)

    2016-04-01

    The Particular intervention plan (PPI in French) is an emergency plan which foresees the measures and means to be implemented to address the potential risks of the presence and operation of a nuclear facility. This plan is implemented and developed by the Prefect in case of nuclear accident (or incident leading to a potential accident), the impact of which extending beyond the facility perimeter. It represents a special section of the organisation plan for civil protection response (ORSEC plan). The PPI foresees the necessary measures and means for crisis management during the first hours following the accident and is triggered by the Department Prefect according to the information provided by the facility operator. Its aim is to protect the populations leaving within 10 km of the facility against a potential radiological hazard. The PPI describes: the facility, the intervention area, the protection measures for the population, the conditions of emergency plan triggering, the crisis organisation, the action forms of the different services, and the post-accident stage. This document is the public version of the Particular intervention plan of the Civaux nuclear power plant (Vienne, France)

  20. Capacity of Lung Stroma to Educate Dendritic Cells Inhibiting Mycobacteria-Specific T-Cell Response Depends upon Genetic Susceptibility to Tuberculosis

    OpenAIRE

    Kapina, Marina A.; Rubakova, Elvira I.; Majorov, Konstantin B.; Logunova, Nadezhda N.; Apt, Alexander S.

    2013-01-01

    The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC) are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg), an essential element of a general...

  1. Geographic Response Information Network : a new tool to manage community information for oil spill contingency planning and response operations

    Energy Technology Data Exchange (ETDEWEB)

    Munger, M.; Bryant, T. [Cook Inlet Regional Citizen' s Advisory Council, Kenai, AK (United States); Haugstad, E.; Kwietniak, J. [Tesora Alaska Petroleum, Kenai, AK (United States); DeCola, E.; Robertson, T. [Nuka Research and Planning Group, Seldovia, AK (United States)

    2006-07-01

    This paper described the Geographic Response Information Network (GRIN) project which was launched to address some of the logistical challenges that often complicate oil spill and emergency response operations. The objective of the project was to develop a computer-based tool for incident logistics to organize maps and data related to oil spills, safety, public relations and basic community resources. In addition to its use for oil spill response planning, the data available can be useful for all-hazards emergency response planning. Early prototypes of the GRIN used PowerPoint slides to organize basic information about coastal communities in Alaska. With time, hyper text markup language (html) was used as the programming format because it can be more readily hyper-linked. Currently, GRIN is organized as a web page with the following 5 categories of information: general, liaison, public information, logistics and safety. There are several sub-headings under each category, such as location, people, economy, subsistence and transportation. This general information allows incident management personnel to obtain a community profile to better understand the cultural, social and economic basis of the community. The GRIN prototype was developed for the Kodiak urban area, but it may be expanded in the future to include other coastal communities in Alaska. 3 refs., 6 figs.

  2. Geographic Response Information Network : a new tool to manage community information for oil spill contingency planning and response operations

    International Nuclear Information System (INIS)

    Munger, M.; Bryant, T.; Haugstad, E.; Kwietniak, J.; DeCola, E.; Robertson, T.

    2006-01-01

    This paper described the Geographic Response Information Network (GRIN) project which was launched to address some of the logistical challenges that often complicate oil spill and emergency response operations. The objective of the project was to develop a computer-based tool for incident logistics to organize maps and data related to oil spills, safety, public relations and basic community resources. In addition to its use for oil spill response planning, the data available can be useful for all-hazards emergency response planning. Early prototypes of the GRIN used PowerPoint slides to organize basic information about coastal communities in Alaska. With time, hyper text markup language (html) was used as the programming format because it can be more readily hyper-linked. Currently, GRIN is organized as a web page with the following 5 categories of information: general, liaison, public information, logistics and safety. There are several sub-headings under each category, such as location, people, economy, subsistence and transportation. This general information allows incident management personnel to obtain a community profile to better understand the cultural, social and economic basis of the community. The GRIN prototype was developed for the Kodiak urban area, but it may be expanded in the future to include other coastal communities in Alaska. 3 refs., 6 figs

  3. Legislative framework on establishing emergency response plan in the case of a nuclear accident

    International Nuclear Information System (INIS)

    Novosel, N.; Valcic, I.; Biscan, R.

    2000-01-01

    To give an overview of the legislative framework, which defined emergency planning in Croatia in the case of a nuclear accident, it's necessary to look at all international recommendations and obligations and the national legislation, acts and regulations. It has to be emphasized that Croatia signed three international conventions in this field, and by that took over some responsibilities and obligations. Beside that, it is also in Croatian interest to follow the recommendations of international institutions such as International Atomic Energy Agency (IAEA standards and technical documents). On the other hand, national legislation in this field consists of several laws, which cover nuclear safety measures, governmental organization, natural disasters and acts (decree, decisions) of responsible authority for emergency planning in the case of a nuclear accident (Ministry of Economy). This paper presents an overview of the international and Croatian legislation which influenced the emergency planning in the case of a nuclear accident. (author)

  4. Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats.

    Science.gov (United States)

    Sánchez-González, Ana; Esnal, Aitor; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto

    2016-03-01

    This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Cortical Inhibition in Attention Deficit Hyperactivity Disorder: New Insights from the Electroencephalographic Response to Transcranial Magnetic Stimulation

    Science.gov (United States)

    Bruckmann, Sarah; Hauk, Daniela; Roessner, Veit; Resch, Franz; Freitag, Christine M.; Kammer, Thomas; Ziemann, Ulf; Rothenberger, Aribert; Weisbrod, Matthias; Bender, Stephan

    2012-01-01

    Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the…

  6. Marine spill response planning for the non-persistent oil transportation industry in Alaska

    International Nuclear Information System (INIS)

    Taylor, E.; Egland, L.

    1998-01-01

    The unique difficulties that face oil spill response planning for the oil transportation industry in Alaska were discussed. Three levels of response strategies and actions proposed by the Alaska Petroleum Distributors and Transporters (APD and T) member companies were reviewed. They were: (1) immediate response (on-board resources), (2) in-region response (caches in Subareas), and (3) out-of-region cascaded resources (from Anchorage and other sources). The strategies and levels of capability were proposed as emergency measures in addition to the more important prevention measures already instituted to prevent discharges of non-persistent oil. 5 refs., 2 tabs., 9 figs

  7. Characteristics of Effective Collaboration in Response to Diversified Transportation Planning Authority

    Directory of Open Access Journals (Sweden)

    John S. Miller

    2011-01-01

    Full Text Available Advantages of decentralized transportation planning responsibilities may include reduced project delivery cost, the integration of comprehensive long-range planning with regional land use, and greater accountability regarding local concerns. Yet disadvantages may include a tendency for operations to dominate longer-term planning, inconsistent operational standards, and difficulty in achieving network benefits, since some transportation links may provide benefits to the entire system but not to the immediate area where the link is located. To surmount these challenges in a decentralized environment, agencies need to cooperate effectively. Characteristics of effective collaboration include (1 experienced personnel, (2 credibility of the deciding entity, (3 transparency of decision-making processes, (4 an authority with sufficient power and/or funding to encourage implementation of key initiatives, (5 clear incentives for cooperation, and, of special importance given limited resources, and (6 an ability to evaluate tradeoffs. An access management case study demonstrates how agencies may use these characteristics to advance challenging projects in a decentralized environment.

  8. Poly(ADP-ribose) polymerase-1 inhibits ATM kinase activity in DNA damage response

    International Nuclear Information System (INIS)

    Watanabe, Fumiaki; Fukazawa, Hidesuke; Masutani, Mitsuko; Suzuki, Hiroshi; Teraoka, Hirobumi; Mizutani, Shuki; Uehara, Yoshimasa

    2004-01-01

    DNA double-strand breaks (DSB) mobilize DNA-repair machinery and cell cycle checkpoint by activating the ataxia-telangiectasia (A-T) mutated (ATM). Here we show that ATM kinase activity is inhibited by poly(ADP-ribose) polymerase-1 (PARP-1) in vitro. It was shown by biochemical fractionation procedure that PARP-1 as well as ATM increases at chromatin level after induction of DSB with neocarzinostatin (NCS). Phosphorylation of histone H2AX on serine 139 and p53 on serine 15 in Parp-1 knockout (Parp-1 -/- ) mouse embryonic fibroblasts (MEF) was significantly induced by NCS treatment compared with MEF derived from wild-type (Parp-1 +/+ ) mouse. NCS-induced phosphorylation of histone H2AX on serine 139 in Parp-1 -/- embryonic stem cell (ES) clones was also higher than that in Parp-1 +/+ ES clone. Furthermore, in vitro, PARP-1 inhibited phosphorylation of p53 on serine 15 and 32 P-incorporation into p53 by ATM in a DNA-dependent manner. These results suggest that PARP-1 negatively regulates ATM kinase activity in response to DSB

  9. Deep Brain Stimulation of the Internal Globus Pallidus Improves Response Initiation and Proactive Inhibition in Patients With Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Yixin Pan

    2018-04-01

    Full Text Available Background: Impulse control disorder is not uncommon in patients with Parkinson’s disease (PD who are treated with dopamine replacement therapy and subthalamic deep brain stimulation (DBS. Internal globus pallidus (GPi-DBS is increasingly used, but its role in inhibitory control has rarely been explored. In this study, we evaluated the effect of GPi-DBS on inhibitory control in PD patients.Methods: A stop-signal paradigm was used to test response initiation, proactive inhibition, and reactive inhibition. The subjects enrolled in the experiment were 27 patients with PD, of whom 13 had received only drug treatment and 14 had received bilateral GPi-DBS in addition to conventional medical treatment and 15 healthy individuals.Results: Our results revealed that with GPi-DBS on, patients with PD showed significantly faster responses than the other groups in trials where it was certain that no stop signal would be presented. Proactive inhibition was significantly different in the surgical patients with GPi-DBS on versus when GPi-DBS was off, in surgical patients with GPi-DBS on versus drug-treated patients, and in healthy controls versus drug-treated patients. Correlation analyses revealed that when GPi-DBS was on, there was a statistically significant moderate positive relationship between proactive inhibition and dopaminergic medication.Conclusion: GPi-DBS may lead to an increase in response initiation speed and improve the dysfunctional proactive inhibitory control observed in PD patients. Our results may help us to understand the role of the GPi in cortical-basal ganglia circuits.

  10. Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus.

    Science.gov (United States)

    Nakagawa, Kei; Inui, Koji; Yuge, Louis; Kakigi, Ryusuke

    2014-11-01

    We previously demonstrated that auditory-evoked cortical responses were suppressed by a weak leading stimulus in a manner similar to the prepulse inhibition (PPI) of startle reflexes. The purpose of the present study was to investigate whether a similar phenomenon was present in the somatosensory system, and also whether this suppression reflected an inhibitory process. We recorded somatosensory-evoked magnetic fields following stimulation of the median nerve and evaluated the extent by which they were suppressed by inserting leading stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold (ST) in healthy participants (Experiment 1). The results obtained demonstrated that activity in the secondary somatosensory cortex in the hemisphere contralateral to the stimulated side (cSII) was significantly suppressed by a weak leading stimulus with the intensity larger than 1.1-fold ST. This result implied that the somatosensory system had an inhibitory process similar to that of PPI. We then presented two successive leading stimuli before the test stimulus, and compared the extent of suppression between the test stimulus-evoked responses and those obtained with the second prepulse alone and with two prepulses (first and second) (Experiment 2). When two prepulses were preceded, cSII responses to the second prepulse were suppressed by the first prepulse, whereas the ability of the second prepulse to suppress the test stimulus remained unchanged. These results suggested the presence of at least two individual pathways; response-generating and inhibitory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. New Tsunami Response, Mitigation, and Recovery Planning "Playbooks" for California (USA) Maritime Communities

    Science.gov (United States)

    Wilson, R. I.; Lynett, P. J.; Miller, K.; Eskijian, M.; Dengler, L. A.; Ayca, A.; Keen, A.; Admire, A. R.; Siegel, J.; Johnson, L. A.; Curtis, E.; Hornick, M.

    2015-12-01

    The 2010 Chile and 2011 Japan tsunamis both struck the California coast offering valuable experience and raised a number of significant issues for harbor masters, port captains, and other maritime entities. There was a general call for more planning products to help guide maritime communities in their tsunami response, mitigation, and recovery activities. The State of California is working with the U.S. Federal Emergency Management Agency (FEMA), the U.S. National Tsunami Hazard Mitigation Program (NTHMP), and other tsunami experts to provide communities with new tsunami planning tools to address these issues: Response Playbooks and plans have been developed for ports and harbors identifying potential tsunami current hazards and related damage for various size events. Maps have been generated showing minor, moderate, and severe damage levels that have been linked to current velocity thresholds of 3, 6, and 9 knots, respectively. Knowing this information allows harbor personnel to move ships or strengthen infrastructure prior to the arrival of distant source tsunamis. Damage probability tools and mitigation plans have been created to help reduce tsunami damage by evaluating the survivability of small and large vessels in harbors and ports. These results were compared to the actual damage assessments performed in California and Japan following the 2011 Japanese tsunami. Fragility curves were developed based on current velocity and direction to help harbor and port officials upgrade docks, piles, and related structures. Guidance documents are being generated to help in the development of both local and statewide recovery plans. Additional tools, like post-tsunami sediment and debris movement models, will allow harbors and ports to better understand if and where recovery issues are most likely to occur. Streamlining the regulatory and environmental review process is also a goal of the guidance. These maritime products and procedures are being integrated into guidance

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  14. Regulation of spatial selectivity by crossover inhibition.

    Science.gov (United States)

    Cafaro, Jon; Rieke, Fred

    2013-04-10

    Signals throughout the nervous system diverge into parallel excitatory and inhibitory pathways that later converge on downstream neurons to control their spike output. Converging excitatory and inhibitory synaptic inputs can exhibit a variety of temporal relationships. A common motif is feedforward inhibition, in which an increase (decrease) in excitatory input precedes a corresponding increase (decrease) in inhibitory input. The delay of inhibitory input relative to excitatory input originates from an extra synapse in the circuit shaping inhibitory input. Another common motif is push-pull or "crossover" inhibition, in which increases (decreases) in excitatory input occur together with decreases (increases) in inhibitory input. Primate On midget ganglion cells receive primarily feedforward inhibition and On parasol cells receive primarily crossover inhibition; this difference provides an opportunity to study how each motif shapes the light responses of cell types that play a key role in visual perception. For full-field stimuli, feedforward inhibition abbreviated and attenuated responses of On midget cells, while crossover inhibition, though plentiful, had surprisingly little impact on the responses of On parasol cells. Spatially structured stimuli, however, could cause excitatory and inhibitory inputs to On parasol cells to increase together, adopting a temporal relation very much like that for feedforward inhibition. In this case, inhibitory inputs substantially abbreviated a cell's spike output. Thus inhibitory input shapes the temporal stimulus selectivity of both midget and parasol ganglion cells, but its impact on responses of parasol cells depends strongly on the spatial structure of the light inputs.

  15. Experience Report: Constraint-Based Modelling and Simulation of Railway Emergency Response Plans

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Sandberg, Lene

    2016-01-01

    ways to proceed, including ways not necessarily anticipated in the paper-based emergency response plans. The case study was undertaken as part of a short research, ProSec, project funded by the Danish Defence Agency, with the aim of applying and developing methods for collaborative mapping of emergency...

  16. Deficits in response inhibition correlate with oculomotor control in children with fetal alcohol spectrum disorder and prenatal alcohol exposure.

    Science.gov (United States)

    Paolozza, Angelina; Rasmussen, Carmen; Pei, Jacqueline; Hanlon-Dearman, Ana; Nikkel, Sarah M; Andrew, Gail; McFarlane, Audrey; Samdup, Dawa; Reynolds, James N

    2014-02-01

    Children with fetal alcohol spectrum disorder (FASD) or prenatal alcohol exposure (PAE) frequently exhibit impairment on tasks measuring inhibition. The objective of this study was to determine if a performance-based relationship exists between psychometric tests and eye movement tasks in children with FASD. Participants for this dataset were aged 5-17 years and included those diagnosed with an FASD (n=72), those with PAE but no clinical FASD diagnosis (n=21), and typically developing controls (n=139). Participants completed a neurobehavioral test battery, which included the NEPSY-II subtests of auditory attention, response set, and inhibition. Each participant completed a series of saccadic eye movement tasks, which included the antisaccade and memory-guided tasks. Both the FASD and the PAE groups performed worse than controls on the subtest measures of attention and inhibition. Compared with controls, the FASD group made more errors on the antisaccade and memory-guided tasks. Among the combined FASD/PAE group, inhibition and switching errors were negatively correlated with direction errors on the antisaccade task but not on the memory-guided task. There were no significant correlations in the control group. These data suggests that response inhibition deficits in children with FASD/PAE are associated with difficulty controlling saccadic eye movements which may point to overlapping brain regions damaged by prenatal alcohol exposure. The results of this study demonstrate that eye movement control tasks directly relate to outcome measures obtained with psychometric tests that are used during FASD diagnosis, and may therefore help with early identification of children who would benefit from a multidisciplinary diagnostic assessment. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Public comments and responses to the 1993 Hanford cleanup five-year plan

    International Nuclear Information System (INIS)

    1993-08-01

    In March 1993, the US Department of Energy, Richland Operations Office (DOE-RL) published its annual Site-Specific Five-Year Plan. The Site-Specific Plan is published to inform the public about the background, status, and plans for Environmental Restoration (ER) and Waste Management (WM) activities at the Hanford site. It is the only document that seeks to bring all ER and WM elements together in one document. The Site-Specific Plan is a companion document to the National Five-Year Plan that deals with all the sites within the DOE complex on a summary level. This Response to Comments document does not try to address every question or concern raised during the public comment period. Some questions were outside the scope of the Five-Year Plan, some we could not decipher, others were variations of the same question. The initial round of public meetings was held in Portland, Oregon, and Seattle, Pasco, and Olympia, Washington. At the request of the Oregon Department of Energy (ODOE) and the Washington State Department of Ecology (Ecology), a second round of meetings was held in Portland and Olympia. Both agencies felt that the first two meetings were held with too little advance notice, and before the Plan could be distributed. Once the public meetings were over and the comment period closed, we then compiled the public comments, largely from audio tapes of the meetings. Individual functions within Hanford were asked to consider and respond to the comments

  18. Ontario Hydro's transportation of radioactive material and emergency response plan

    International Nuclear Information System (INIS)

    Karmali, N.

    1993-01-01

    Ontario Hydro has been transporting radioactive material for almost 30 years without any exposure to the public or release to the environment. However, there have been three accidents involving Hydro's shipments of radioactive material. In addition to the quality packaging and shipping program, Ontario Hydro has an Emergency Response Plan and capability to deal with an accident involving a shipment of radioactive material. The Corporation's ability to respond, to effectively control and contain the situation, site remediation, and to provide emergency public information in the event of a road accident minimizes the risk to the public and the environment. This emphasizes their commitment to worker safety, public safety and impact to the environment. Response capability is mandated under various legislation and regulations in Canada

  19. Food-cue affected motor response inhibition and self-reported dieting success: a pictorial affective shifting task

    Directory of Open Access Journals (Sweden)

    Adrian eMeule

    2014-03-01

    Full Text Available Behavioral inhibition is one of the basic facets of executive functioning and is closely related to self-regulation. Impulsive reactions, i.e. low inhibitory control, have been associated with higher body-mass-index (BMI, binge eating, and other problem behaviors (e.g. substance abuse, pathological gambling, etc.. Nevertheless, studies which investigated the direct influence of food-cues on behavioral inhibition have been fairly inconsistent. In the current studies, we investigated food-cue affected behavioral inhibition in young women. For this purpose, we used a go/no-go task with pictorial food and neutral stimuli in which stimulus-response mapping is reversed after every other block (affective shifting task. In study 1, hungry participants showed faster reaction times to and omitted fewer food than neutral targets. Low dieting success and higher BMI were associated with behavioral disinhibition in food relative to neutral blocks. In study 2, both hungry and satiated individuals were investigated. Satiation did not influence overall task performance, but modulated associations of task performance with dieting success and self-reported impulsivity. When satiated, increased food craving during the task was associated with low dieting success, possibly indicating a preload-disinhibition effect following food intake. Food-cues elicited automatic action and approach tendencies regardless of dieting success, self-reported impulsivity, or current hunger levels. Yet, associations between dieting success, impulsivity, and behavioral food-cue responses were modulated by hunger and satiation. Future research investigating clinical samples and including other salient non-food stimuli as control category is warranted.

  20. Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhi, Wenbing; Liu, Fang; He, Zehong; Wang, Xiuei; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn

    2017-04-01

    Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I. - Highlights: • AO-I inhibited Ox-LDL-induced VSMCs proliferation and migration. • AO-I alleviated inflammatory response via inhibiting TNF-α, IL-6 and NO production. • AO-I restored HO-1 expression and down-regulated PCNA expression. • MCP-1 overexpression is potentially regulated by NF-κB and p38 MAPK pathway. • AO-I possesses strong anti-lipid peroxidation effect.

  1. Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

    Science.gov (United States)

    Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

    2011-01-01

    Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

  2. Report to Congress on status of emergency response planning for nuclear power plants

    International Nuclear Information System (INIS)

    1981-03-01

    This report responds to a request (Public Law 96-295, Section 109) for the Nuclear Regulatory Commission (NRC) to report to Congress on the status of emergency response planning in support of nuclear power reactors. The report includes information on the status of this planning as well as on the Commission actions relating to emergency preparedness. These actions include a summary of the new regulatory requirements and the preliminary results of two comprehensive Evacuation Time Estimate studies; one requested by the NRC including 50 nuclear power plant sites and one conducted by the Federal Emergency Management Agency (FEMA) for 12 high population density sites. FEMA provided the information in this report on the status of State and local planning, including projected schedules for joint State/county/licensee emergency preparedness exercises. Included as Appendicies are the NRC Emergency Planning Final Regulations, 10 CFR Part 50 (45 FR 55402), the FEMA Proposed Rule, 'Review and Approval of State and Local Radiological Emergency Plans and Preparedness', 44 CFR Part 350 (45 FR 42341) and the NRC/FEMA Memorandums of Understanding

  3. Introduction of an Emergency Response Plan for flood loading of Sultan Abu Bakar Dam in Malaysia

    Science.gov (United States)

    Said, N. F. Md; Sidek, L. M.; Basri, H.; Muda, R. S.; Razad, A. Z. Abdul

    2016-03-01

    Sultan Abu Bakar Dam Emergency Response Plan (ERP) is designed to assist employees for identifying, monitoring, responding and mitigation dam safety emergencies. This paper is outlined to identification of an organization chart, responsibility for emergency management team and triggering level in Sultan Abu Bakar Dam ERP. ERP is a plan that guides responsibilities for proper operation of Sultan Abu Bakar Dam in respond to emergency incidents affecting the dam. Based on this study four major responsibilities are needed for Abu Bakar Dam owing to protect any probable risk for downstream which they can be Incident Commander, Deputy Incident Commander, On-Scene Commander, Civil Engineer. In conclusion, having organization charts based on ERP studies can be helpful for decreasing the probable risks in any projects such as Abu Bakar Dam and it is a way to identify and suspected and actual dam safety emergencies.

  4. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

    Directory of Open Access Journals (Sweden)

    Jody Groenendyk

    Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

  5. Inhibition of EGFR or IGF-1R signaling enhances radiation response in head and neck cancer models but concurrent inhibition has no added benefit

    International Nuclear Information System (INIS)

    Raju, Uma; Molkentine, David P; Valdecanas, David R; Deorukhkar, Amit; Mason, Kathryn A; Buchholz, Thomas A; Meyn, Raymond E; Ang, Kie-Kian; Skinner, Heath

    2015-01-01

    Interaction between the epidermal growth factor receptor (EGFR) and the insulin-like growth factor receptor (IGF-1R) has been well established in many cancer types. We investigated the effects of cetuximab (EGFR antibody) and IMC-A12 (IGF-1R antibody) on the response of head and neck squamous cell carcinoma (HNSCC) to radiation therapy (RT). The effects of cetuximab and IMC-A12 on cell viability and radiosensitivity were determined by clonogenic cell survival assay. Formation of nuclear γ-H2AX and 53BP1 foci was monitored by immunofluorescence. Alterations in target signaling were analyzed by Western blots. In vivo tumor growth delay assay was performed to determine the efficacy of triple therapy with IMC-A12, cetuximab, and RT. In vitro data showed that cetuximab differentially affected the survival and the radiosensitivity of HNSCC cells. Cetuximab suppressed DNA repair that was evident by the prolonged presence of nuclear γ-H2AX and 53BP1 foci. IMC-A12 did not have any effect on the cell survival. However, it increased the radiosensitivity of one of the cell lines. EGFR inhibition increased IGF-1R expression levels and also the association between EGFR and IGF-1R. Addition of IMC-A12 to cetuximab did not increase the radiosensitivity of these cells. Tumor xenografts exhibited enhanced response to RT in the presence of either cetuximab or IMC-A12. Concurrent treatment regimen failed to further enhance the tumor response to cetuximab and/or RT. Taken together our data suggest that concomitant inhibition of both EGFR and IGF-1R pathways did not yield additional therapeutic benefit in overcoming resistance to RT

  6. Lactoferricin B Inhibits the Phosphorylation of the Two-Component System Response Regulators BasR and CreB*

    Science.gov (United States)

    Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng

    2012-01-01

    Natural antimicrobial peptides provide fundamental protection for multicellular organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have shown that Lfcin B penetrates the cell membrane and has intracellular activities. To elucidate the intracellular behavior of Lfcin B, we first used Escherichia coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system. For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli's tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of a two-component system directly. PMID:22138548

  7. Lactoferricin B inhibits the phosphorylation of the two-component system response regulators BasR and CreB.

    Science.gov (United States)

    Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng

    2012-04-01

    Natural antimicrobial peptides provide fundamental protection for multicellular organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have shown that Lfcin B penetrates the cell membrane and has intracellular activities. To elucidate the intracellular behavior of Lfcin B, we first used Escherichia coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system. For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli's tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of a two-component system directly.

  8. Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.

    Science.gov (United States)

    Albariño, César G; Wiggleton Guerrero, Lisa; Spengler, Jessica R; Uebelhoer, Luke S; Chakrabarti, Ayan K; Nichol, Stuart T; Towner, Jonathan S

    2015-02-01

    Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses. Published by Elsevier Inc.

  9. Inhibition in the Human Auditory Cortex.

    Directory of Open Access Journals (Sweden)

    Koji Inui

    Full Text Available Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

  10. 20 CFR 641.310 - May the Governor delegate responsibility for developing and submitting the State Plan?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false May the Governor delegate responsibility for developing and submitting the State Plan? 641.310 Section 641.310 Employees' Benefits EMPLOYMENT AND TRAINING... developing and submitting the State Plan, provided that any such delegation is consistent with State law and...

  11. Screening of traditional Chinese medicines with therapeutic potential on chronic obstructive pulmonary disease through inhibiting oxidative stress and inflammatory response.

    Science.gov (United States)

    Zhou, Ming-Xing; Wei, Xuan; Li, Ai-Ling; Wang, Ai-Min; Lu, Ling-Zi; Yang, Yue; Ren, Dong-Mei; Wang, Xiao-Ning; Wen, Xue-Sen; Lou, Hong-Xiang; Shen, Tao

    2016-09-13

    Chronic obstructive pulmonary disease (COPD) is a major public health problem and gives arise to severe chronic morbidity and mortality in the world. Inflammatory response and oxidative stress play dominant roles in the pathological mechanism of COPD, and have been regarded to be two important targets for the COPD therapy. Traditional Chinese medicines (TCMs) possess satisfying curative effects on COPD under guidance of the TCM theory in China, and merit in-depth investigations as a resource of lead compounds. One hundred ninety-six of TCMs were collected, and extracted to establish a TCM extract library, and then further evaluated for their potency on inhibitions of oxidative stress and inflammatory response using NADP(H):quinone oxidoreductase (QR) assay and nitric oxide (NO) production assay, respectively. Our investigation observed that 38 of the tested TCM extracts induced QR activity in hepa 1c1c7 murine hepatoma cells, and 55 of them inhibited NO production in RAW 264.7 murine macrophages at the tested concentrations. Noteworthily, 20 of TCM extracts simultaneously inhibited oxidative stress and inflammatory responses. The observed bioactive TCMs, particularly these 20 TCMs with dual inhibitory effects, might be useful for the treatment of COPD. More importantly, the results of the present research afford us an opportunity to discover new lead molecules as COPD therapeutic agents from these active TCMs.

  12. ANSI/ANS-8.23-1997: nuclear criticality accident emergency planning and response

    International Nuclear Information System (INIS)

    Baker, J.S.

    2004-01-01

    American National Standard ANSUANS-8.23 was developed to expand upon the basic emergency response guidance given in American National Standard, 'Administrative Practices for Nuclear Criticality Safety' ANSI/ANS-8.19-1996 (Ref. 1). This standard provides guidance for minimizing risks to personnel during emergency response to a nuclear criticality accident outside reactors. This standard is intended to apply to those facilities for which a criticality accident alarm system, as specified in American National Standard, 'Criticality Accident Alarm System', ANSI/ANS-8.3-1997 (Ref. 2) is in use. The Working Group was established in 1990, with Norman L. Pruvost as chairman. The Working Group had up to twenty-three members representing a broad range of the nuclear industry, and has included members from Canada, Japan and the United Kingdom. The initial edition of ANSI/ANS-8.23 was approved by the American National Standards Institute on December 30, 1997. It provides guidance for the following topics: (1) Management and technical staff responsibilities; (2) Evaluation of a potential criticality accident; (3) Emergency plan provisions; (4) Evacuation; (5) Re-entry, rescue and stabilization; and (6) Classroom training, exercises and evacuation drills. This guidance is not for generic emergency planning issues, but is specific to nuclear criticality accidents. For example, it assumes that an Emergency Plan is already established at facilities that implement the standard. During the development of the initial edition of ANSI/ANS-8.23, each Working Group member evaluated potential use of the standard at a facility with which the member was familiar. This revealed areas where a facility could have difficulty complying with the standard. These reviews helped identify and eliminate many potential problems and ambiguities with the guidance. The Working Group has received very limited feedback from the user community since the first edition of the standard was published. Suggestions

  13. Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Hassan, Saima; Esch, Amanda; Liby, Tiera; Gray, Joe W; Heiser, Laura M

    2017-12-01

    Effective treatment of patients with triple-negative (ER-negative, PR-negative, HER2-negative) breast cancer remains a challenge. Although PARP inhibitors are being evaluated in clinical trials, biomarkers are needed to identify patients who will most benefit from anti-PARP therapy. We determined the responses of three PARP inhibitors (veliparib, olaparib, and talazoparib) in a panel of eight triple-negative breast cancer cell lines. Therapeutic responses and cellular phenotypes were elucidated using high-content imaging and quantitative immunofluorescence to assess markers of DNA damage (53BP1) and apoptosis (cleaved PARP). We determined the pharmacodynamic changes as percentage of cells positive for 53BP1, mean number of 53BP1 foci per cell, and percentage of cells positive for cleaved PARP. Inspired by traditional dose-response measures of cell viability, an EC 50 value was calculated for each cellular phenotype and each PARP inhibitor. The EC 50 values for both 53BP1 metrics strongly correlated with IC 50 values for each PARP inhibitor. Pathway enrichment analysis identified a set of DNA repair and cell cycle-associated genes that were associated with 53BP1 response following PARP inhibition. The overall accuracy of our 63 gene set in predicting response to olaparib in seven breast cancer patient-derived xenograft tumors was 86%. In triple-negative breast cancer patients who had not received anti-PARP therapy, the predicted response rate of our gene signature was 45%. These results indicate that 53BP1 is a biomarker of response to anti-PARP therapy in the laboratory, and our DNA damage response gene signature may be used to identify patients who are most likely to respond to PARP inhibition. Mol Cancer Ther; 16(12); 2892-901. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Constraining Influence Diagram Structure by Generative Planning: An Application to the Optimization of Oil Spill Response

    OpenAIRE

    Agosta, John Mark

    2013-01-01

    This paper works through the optimization of a real world planning problem, with a combination of a generative planning tool and an influence diagram solver. The problem is taken from an existing application in the domain of oil spill emergency response. The planning agent manages constraints that order sets of feasible equipment employment actions. This is mapped at an intermediate level of abstraction onto an influence diagram. In addition, the planner can apply a surveillance operator that...

  15. Autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

    Science.gov (United States)

    Xie, Xiaolei; Le, Li; Fan, Yanxin; Lv, Lin; Zhang, Junjie

    2012-07-01

    Mitoribosome in mammalian cells is responsible for synthesis of 13 mtDNA-encoded proteins, which are integral parts of four mitochondrial respiratory chain complexes (I, III, IV and V). ERAL1 is a nuclear-encoded GTPase important for the formation of the 28S small mitoribosomal subunit. Here, we demonstrate that knockdown of ERAL1 by RNA interference inhibits mitochondrial protein synthesis and promotes reactive oxygen species (ROS) generation, leading to autophagic vacuolization in HeLa cells. Cells that lack ERAL1 expression showed a significant conversion of LC3-I to LC3-II and an enhanced accumulation of autophagic vacuoles carrying the LC3 marker, all of which were blocked by the autophagy inhibitor 3-MA as well as by the ROS scavenger NAC. Inhibition of mitochondrial protein synthesis either by ERAL1 siRNA or chloramphenicol (CAP), a specific inhibitor of mitoribosomes, induced autophagy in HTC-116 TP53 (+/+) cells, but not in HTC-116 TP53 (-/-) cells, indicating that tumor protein 53 (TP53) is essential for the autophagy induction. The ROS elevation resulting from mitochondrial protein synthesis inhibition induced TP53 expression at transcriptional levels by enhancing TP53 promoter activity, and increased TP53 protein stability by suppressing TP53 ubiquitination through MAPK14/p38 MAPK-mediated TP53 phosphorylation. Upregulation of TP53 and its downstream target gene DRAM1, but not CDKN1A/p21, was required for the autophagy induction in ERAL1 siRNA or CAP-treated cells. Altogether, these data indicate that autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

  16. Indian Point Nuclear Power Station: verification analysis of County Radiological Emergency-Response Plans

    International Nuclear Information System (INIS)

    Nagle, J.; Whitfield, R.

    1983-05-01

    This report was developed as a management tool for use by the Federal Emergency Management Agency (FEMA) Region II staff. The analysis summarized in this report was undertaken to verify the extent to which procedures, training programs, and resources set forth in the County Radiological Emergency Response Plans (CRERPs) for Orange, Putnam, and Westchester counties in New York had been realized prior to the March 9, 1983, exercise of the Indian Point Nuclear Power Station near Buchanan, New York. To this end, a telephone survey of county emergency response organizations was conducted between January 19 and February 22, 1983. This report presents the results of responses obtained from this survey of county emergency response organizations

  17. Oak Ridge National Laboratory Corrective Action Plan in response to Tiger Team assessment. Volume 1, Revision 5

    Energy Technology Data Exchange (ETDEWEB)

    Kuliasha, Michael A.

    1991-08-23

    This report presents a complete response to the Tiger Team assessment that was conducted at Oak Ridge National Laboratory (ORNL) and at the US Department of Energy (DOE) Oak Ridge Operations Office (ORO) from October 22, 1990, through November 30, 1990. The action plans have undergone both a discipline review and a cross-cutting review with respect to root cause. In addition, the action plans have been integrated with initiatives being pursued across Martin Marietta Energy Systems, Inc., in response to Tiger Team findings at other DOE facilities operated by Energy Systems. The root cause section is complete and describes how ORNL intends to address the root causes of the findings identified during the assessment. The action plan has benefited from a complete review by various offices at DOE Headquarters as well as review by the Tiger Team that conducted the assessment to ensure that the described actions are responsive to the observed problems.

  18. Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

    International Nuclear Information System (INIS)

    Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi; Rhim, Hyangshuk; Bae, Yong Soo; Choi, Soo Young; Park, Jinseu

    2014-01-01

    HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction

  19. Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Rhim, Hyangshuk [Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Bae, Yong Soo [Department of Biological Science, College of Natural Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Choi, Soo Young [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Park, Jinseu, E-mail: jinpark@hallym.ac.kr [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2014-10-01

    HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction.

  20. High surface adsorption properties of carbon-based nanomaterials are responsible for mortality, swimming inhibition, and biochemical responses in Artemia salina larvae

    International Nuclear Information System (INIS)

    Mesarič, Tina; Gambardella, Chiara; Milivojević, Tamara; Faimali, Marco; Drobne, Damjana; Falugi, Carla; Makovec, Darko; Jemec, Anita; Sepčić, Kristina

    2015-01-01

    Highlights: • Carbon-based nanomaterials adsorb onto the body surface of A. salina larvae. • Surface adsorption results in concentration–dependent inhibition of larval swimming. • Carbon-based nanomaterials induce no significant mortality of A. salina larvae. - Abstract: We investigated the effects of three different carbon-based nanomaterials on brine shrimp (Artemia salina) larvae. The larvae were exposed to different concentrations of carbon black, graphene oxide, and multiwall carbon nanotubes for 48 h, and observed using phase contrast and scanning electron microscopy. Acute (mortality) and behavioural (swimming speed alteration) responses and cholinesterase, glutathione-S-transferase and catalase enzyme activities were evaluated. These nanomaterials were ingested and concentrated in the gut, and attached onto the body surface of the A. salina larvae. This attachment was responsible for concentration–dependent inhibition of larval swimming, and partly for alterations in the enzyme activities, that differed according to the type of tested nanomaterials. No lethal effects were observed up to 0.5 mg/mL carbon black and 0.1 mg/mL multiwall carbon nanotubes, while graphene oxide showed a threshold whereby it had no effects at 0.6 mg/mL, and more than 90% mortality at 0.7 mg/mL. Risk quotients calculated on the basis of predicted environmental concentrations indicate that carbon black and multiwall carbon nanotubes currently do not pose a serious risk to the marine environment, however if uncontrolled release of nanomaterials continues, this scenario can rapidly change

  1. High surface adsorption properties of carbon-based nanomaterials are responsible for mortality, swimming inhibition, and biochemical responses in Artemia salina larvae

    Energy Technology Data Exchange (ETDEWEB)

    Mesarič, Tina, E-mail: tina.mesaric84@gmail.com [Department of Biology, Biotechnical Faculty, University of Ljubljana (Slovenia); Gambardella, Chiara, E-mail: chiara.gambardella@ge.ismar.cnr.it [Institute of Marine Sciences, National Research Council, Genova (Italy); Milivojević, Tamara, E-mail: milivojevictamara@gmail.com [Department of Biology, Biotechnical Faculty, University of Ljubljana (Slovenia); Faimali, Marco, E-mail: marco.faimali@ismar.cnr.it [Institute of Marine Sciences, National Research Council, Genova (Italy); Drobne, Damjana, E-mail: damjana.drobne@bf.uni-lj.si [Department of Biology, Biotechnical Faculty, University of Ljubljana (Slovenia); Centre of Excellence in Nanoscience and Nanotechnology (CO Nanocentre), Ljubljana (Slovenia); Centre of Excellence in Advanced Materials and Technologies for the Future (CO NAMASTE), Ljubljana (Slovenia); Falugi, Carla, E-mail: carlafalugi@hotmail.it [Department of Earth, Environment and Life Sciences, University of Genova, Genova (Italy); Makovec, Darko, E-mail: darko.makovec@ijs.si [Jožef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Jemec, Anita, E-mail: anita.jemec@bf.uni-lj.si [Department of Biology, Biotechnical Faculty, University of Ljubljana (Slovenia); Sepčić, Kristina, E-mail: kristina.sepcic@bf.uni-lj.si [Department of Biology, Biotechnical Faculty, University of Ljubljana (Slovenia)

    2015-06-15

    Highlights: • Carbon-based nanomaterials adsorb onto the body surface of A. salina larvae. • Surface adsorption results in concentration–dependent inhibition of larval swimming. • Carbon-based nanomaterials induce no significant mortality of A. salina larvae. - Abstract: We investigated the effects of three different carbon-based nanomaterials on brine shrimp (Artemia salina) larvae. The larvae were exposed to different concentrations of carbon black, graphene oxide, and multiwall carbon nanotubes for 48 h, and observed using phase contrast and scanning electron microscopy. Acute (mortality) and behavioural (swimming speed alteration) responses and cholinesterase, glutathione-S-transferase and catalase enzyme activities were evaluated. These nanomaterials were ingested and concentrated in the gut, and attached onto the body surface of the A. salina larvae. This attachment was responsible for concentration–dependent inhibition of larval swimming, and partly for alterations in the enzyme activities, that differed according to the type of tested nanomaterials. No lethal effects were observed up to 0.5 mg/mL carbon black and 0.1 mg/mL multiwall carbon nanotubes, while graphene oxide showed a threshold whereby it had no effects at 0.6 mg/mL, and more than 90% mortality at 0.7 mg/mL. Risk quotients calculated on the basis of predicted environmental concentrations indicate that carbon black and multiwall carbon nanotubes currently do not pose a serious risk to the marine environment, however if uncontrolled release of nanomaterials continues, this scenario can rapidly change.

  2. Methanol Extract of Myelophycus caespitosus Inhibits the ...

    African Journals Online (AJOL)

    Methanol Extract of Myelophycus caespitosus Inhibits the Inflammatory Response in Lipopolysaccharidestimulated BV2 Microglial Cells by Downregulating NF-kB via Inhibition of the Akt Signaling Pathway.

  3. 40 CFR 300.440 - Procedures for planning and implementing off-site response actions.

    Science.gov (United States)

    2010-07-01

    ... unless the Remedial Project Manager or OSC assures the proper management of the CERCLA waste samples or... OIL AND HAZARDOUS SUBSTANCES POLLUTION CONTINGENCY PLAN Hazardous Substance Response § 300.440... § 300.440(d). (5) Off-site transfers of those laboratory samples and treatability study CERCLA wastes...

  4. Influence of norepinephrine transporter inhibition on hemodynamic response to hypergravitation

    OpenAIRE

    Strempel, Sebastian

    2011-01-01

    Background: Sympathetically-mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness (g-LOC). Norepinephrine transporter (NET) inhibition prevents neurally-mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus, it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. Methods. We performed a double-blind, randomized...

  5. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  6. 20 CFR 1002.261 - Who is responsible for funding any plan obligation to provide the employee with pension benefits?

    Science.gov (United States)

    2010-04-01

    ... obligation to provide the employee with pension benefits? 1002.261 Section 1002.261 Employees' Benefits... and Benefits Pension Plan Benefits § 1002.261 Who is responsible for funding any plan obligation to provide the employee with pension benefits? With the exception of multiemployer plans, which have separate...

  7. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  8. Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

    Science.gov (United States)

    Yang, Zhong-Bao; He, Chunmei; Ma, Yanqi; Herde, Marco; Ding, Zhaojun

    2017-02-01

    Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. © 2017 American Society of Plant Biologists. All Rights Reserved.

  9. Review of off-site emergency preparedness and response plan of Indian NPPs based on experience of Fukushima nuclear accident

    International Nuclear Information System (INIS)

    Singh, Hukum; Dash, M.; Shukla, Vikas; Vijayan, P.; Krishnamurthy, P.R.

    2012-01-01

    Nuclear power plants in India are designed, constructed and operated based on the principle of the highest priority to nuclear safety. To deal with any unlikely situation of radiological emergency, the emergency preparedness and response plans are ensured to be in place at all NPPs prior to their commissioning. These plans are periodically reviewed and tested by conducting emergency exercise with the participation of various agencies such as Nuclear Power Corporation of India Limited, NDMA, district authorities, regulatory body and general public. On March 11, 2011 an earthquake of magnitude 9.0 hit the Fukushima Dai-ichi and Dai-ni followed by tsunami waves of height 15 meters above reference sea level. This resulted in large scale release of radioactive material from Fukushima Dai-ichi NPS. This led to the evacuation of a large number of people from the areas surrounding the affected nuclear power plants. The event was rated as level 7 event in International Nuclear Event Scale (INES). The event also revealed the challenges in handling radiological emergency situation in adverse environmental conditions, The experience of managing radiological emergency situation during Fukushima nuclear accident provides opportunities to review and improve emergency preparedness and response programme. The present paper presents the chronology of the emergency situation, challenges faced and handled in Fukushima. Even though the possibility of a Fukushima type nuclear accident in India is very remote due to the low probability of a high intensity earthquake followed by tsunami at NPP sites, the efforts needs to be initiated from the regulatory point of view for an effective Nuclear and Radiological Emergency Preparedness and Response Plans. The Emergency Preparedness and Response Plans of NPP sites were reviewed in the light of unique challenges of accident at Fukushima. It is realized that multi unit events are the realities that must be addressed as part of Emergency

  10. Review of off-site emergency preparedness and response plan of Indian NPPs based on experience of Fukushima nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Hukum; Dash, M.; Shukla, Vikas; Vijayan, P.; Krishnamurthy, P.R., E-mail: vshukla@aerb.gov.in [Operating Plants Safety Division, Atomic Energy Regulatory Board, Mumbai (India)

    2012-07-01

    Nuclear power plants in India are designed, constructed and operated based on the principle of the highest priority to nuclear safety. To deal with any unlikely situation of radiological emergency, the emergency preparedness and response plans are ensured to be in place at all NPPs prior to their commissioning. These plans are periodically reviewed and tested by conducting emergency exercise with the participation of various agencies such as Nuclear Power Corporation of India Limited, NDMA, district authorities, regulatory body and general public. On March 11, 2011 an earthquake of magnitude 9.0 hit the Fukushima Dai-ichi and Dai-ni followed by tsunami waves of height 15 meters above reference sea level. This resulted in large scale release of radioactive material from Fukushima Dai-ichi NPS. This led to the evacuation of a large number of people from the areas surrounding the affected nuclear power plants. The event was rated as level 7 event in International Nuclear Event Scale (INES). The event also revealed the challenges in handling radiological emergency situation in adverse environmental conditions, The experience of managing radiological emergency situation during Fukushima nuclear accident provides opportunities to review and improve emergency preparedness and response programme. The present paper presents the chronology of the emergency situation, challenges faced and handled in Fukushima. Even though the possibility of a Fukushima type nuclear accident in India is very remote due to the low probability of a high intensity earthquake followed by tsunami at NPP sites, the efforts needs to be initiated from the regulatory point of view for an effective Nuclear and Radiological Emergency Preparedness and Response Plans. The Emergency Preparedness and Response Plans of NPP sites were reviewed in the light of unique challenges of accident at Fukushima. It is realized that multi unit events are the realities that must be addressed as part of Emergency

  11. The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model

    Directory of Open Access Journals (Sweden)

    Paiboon Jungsuwadee

    2012-08-01

    Full Text Available MnTE-2-PyP, a superoxide dismutase mimetic, inhibited OVA-induced airway inflammation in mice suggesting an effect on Th2 responsiveness. Thus, we hypothesized that MnTE-2-PyP may alter dendritic cell-Th2 interactions. Bone marrow derived dendritic cells (DC and OVA323-339-specific Th2 cells were cultured separately in the presence or absence of MnTE-2-PyP for 3 days prior to the co-culturing of the two cell types in the presence of an OVA323-339 peptide and in some cases stimulated with CD3/CD28. MnTE-2-PyP-pretreated DC inhibited IL-4, IL-5 and IFNγ production and inhibited Th2 cell proliferation in the DC-Th2 co-culturing system in the presence of the OVA323-339 peptide. Similar results were obtained using the CD3/CD28 cell-activation system; the addition of MnTE-2-PyP inhibited Th2 cell proliferation. MnTE-2-PyP suppressed CD25 expression on OVA-specific Th2 cells, which implied that MnTE-2-PyP can inhibit the activation of Th2 cells. MnTE-2-PyP also down-regulated co-stimulatory molecules: CD40, CD80 and CD86 on immature DC. Our studies suggest that the major mechanism by which MnTE-2-PyP inhibits airway inflammation is by acting on the DC and suppressing Th2 cell proliferation and activation.

  12. The active sequence in the acth molecule responsible for inhibition of the extinction of conditioned avoidance behaviour in rats

    NARCIS (Netherlands)

    Greven, H.M.; Wied, D. de

    1967-01-01

    The effect of structural analogues of the N-terminal decapeptide of ACTH on inhibition of extinction of a conditioned avoidance response in rats has been studied. Studies involving the relation between chain length and behavioural activity revealed that the sequence 4–10 is the shortest peptide

  13. Implementation of Capacity Planning Agent of Demand Responsive Planning Framework : Master’s Thesis in Production Engineering of The Royal Institute of Technology

    OpenAIRE

    Juhong, Nirut

    2013-01-01

    This master’s thesis is conducted as a conclusion of Master degree of Science in Production Engineering and Management at The Royal Institute of Technology. The focus of this thesis work is to implement a Capacity planning agent. Nowadays, companies need to adapt themselves to be as responsive to customers’ demand as possible. However, the responsiveness is usually limited by the fixed capacity of the production. Evolvable Production System (EPS), motivated by the limitation mentioned above, ...

  14. ARAC: a centralized computer assisted emergency planning, response, and assessment system for atmospheric releases of toxic material

    International Nuclear Information System (INIS)

    Dickerson, M.H.; Knox, J.B.

    1986-10-01

    The Atmospheric Release Advisory Capability (ARAC) is an emergency planning, response, and assessment service, developed by the US Departments of Energy and Defense, and focused, thus far, on atmospheric releases of nuclear material. For the past 14 years ARAC has responded to over 150 accidents, potential accidents, and major exercises. The most notable accident responses are the COSMOS 954 reentry, the Three Mile Island (TMI-2) accident and subsequent purge of 85 Kr from the containment vessel, the recent UF 6 accident at the Kerr-McGee Plant, Gore, Oklahoma, and the Chernobyl nuclear reactor accident in the Soviet Union. Based on experience in the area of emergency response, developed during the past 14 years, this paper describes the cost effectiveness and other advantages of a centralized emergency planning, response, and assessment service for atmospheric releases of nuclear material

  15. ARAC: a centralized computer-assisted emergency planning, response, and assessment system for atmospheric releases of toxic material

    International Nuclear Information System (INIS)

    Dickerson, M.H.; Knox, J.B.

    1987-01-01

    The Atmospheric Release Advisory Capability (ARAC) is an emergency planning, response, and assessment service, developed by the US Departments of Energy and Defense, and focused, thus far, on atmospheric releases of nuclear material. For the past 14 years ARAC has responded to over 150 accidents, potential accidents, and major exercises. The most notable accident responses are the COSMOS 954 reentry, the Three Mile Island (TMI-2) accident and subsequent purge of 85 Kr from the containment vessel, the recent UF 6 accident at the Kerr-McGee Plant, Gore, Oklahoma, and the Chernobyl nuclear reactor accident in the Soviet Union. Based on experience in the area of emergency response, developed during the past 14 years, this paper describes the cost effectiveness and other advantages of a centralized emergency planning, response, and assessment service for atmospheric releases of nuclear material

  16. Building a year 2000 emergency response plan

    International Nuclear Information System (INIS)

    Riopel, P.

    1998-01-01

    This presentation emphasized the importance of developing an emergency plan to minimize any impacts in the event that something may go wrong when the clock changes over at midnight on December 31, 1999. It is usually impossible to anticipate what kinds of emergencies will happen. Planning for emergencies does not have to be an intimidating task. Hazard analysis is a subjective way to investigate what can go wrong, the likelihood of it happening relative to some other potential emergency, and the seriousness of the event. In general, emergency planning for Y2K should not be significantly different from planning for any other type of emergency. Y2K is not the emergency. The events that occur as a consequence of Y2K are. It is these events that should be the focus of a Year 2000 emergency plan

  17. Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition

    NARCIS (Netherlands)

    van der Meer, Dennis; Hartman, Catharina A.; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

    2017-01-01

    Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that

  18. Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition

    NARCIS (Netherlands)

    Meer, D. van der; Hartman, C.A.; Rooij, D. van; Franke, B.; Heslenfeld, D.J.; Oosterlaan, J.; Faraone, S.V; Buitelaar, J.K.; Hoekstra, P.J.

    2017-01-01

    BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that

  19. Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition

    NARCIS (Netherlands)

    van der Meer, Dennis; Hartman, Catharina A.; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

    Background Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that

  20. Potentiation of the vascular response to kinins by inhibition of myocardial kininases.

    Science.gov (United States)

    Dendorfer, A; Wolfrum, S; Schäfer, U; Stewart, J M; Inamura, N; Dominiak, P

    2000-01-01

    Inhibitors of angiotensin I-converting enzyme (ACE) are very efficacious in the potentiation of the actions of bradykinin (BK) and are able to provoke a B(2) receptor-mediated vasodilation even after desensitization of this receptor. Because this activity cannot be easily explained only by an inhibition of kinin degradation, direct interactions of ACE inhibitors with the B(2) receptor or its signal transduction have been hypothesized. To clarify the significance of degradation-independent potentiation, we studied the vasodilatory effects of BK and 2 degradation-resistant B(2) receptor agonists in the isolated rat heart, a model in which ACE and aminopeptidase P (APP) contribute equally to the degradation of BK. Coronary vasodilation to BK and to a peptidic (B6014) and a nonpeptidic (FR190997) degradation-resistant B(2) agonist was assessed in the presence or absence of the ACE inhibitor ramiprilat, the APP inhibitor mercaptoethanol, or both. Ramiprilat or mercaptoethanol induced leftward shifts in the BK dose-response curve (EC(50)=3.4 nmol/L) by a factor of 4.6 or 4.9, respectively. Combined inhibition of ACE and APP reduced the EC(50) of BK to 0.18 nmol/L (ie, by a factor of 19) but potentiated the activity of B6014 (EC(50)=1.9 nmol/L) only weakly without altering that of FR190997 (EC(50)=0.34 nmol/L). Desensitization of B(2) receptors was induced by the administration of BK (0.2 micromol/L) or FR190997 (0.1 micromol/L) for 30 minutes; the vascular reactivity to ramiprilat or increasing doses of BK was tested thereafter. After desensitization with BK, but not FR190997, an additional application of ramiprilat provoked a B(2) receptor-mediated vasodilation. High BK concentrations were still effective at the desensitized receptor. The process of desensitization was not altered by ramiprilat. These results show that in this model, all potentiating actions of ACE inhibitors on kinin-induced vasodilation are exclusively related to the reduction in BK breakdown and are

  1. Motor deficits, impaired response inhibition, and blunted response to methylphenidate following neonatal exposure to decabromodiphenyl ether.

    Science.gov (United States)

    Markowski, Vincent P; Miller-Rhodes, Patrick; Cheung, Randy; Goeke, Calla; Pecoraro, Vincent; Cohen, Gideon; Small, Deena J

    2017-09-01

    Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that is widely-used in electronic equipment. After decades of use, decaBDE and other members of its polybrominated diphenyl ether class have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Although it has been banned in Europe and voluntarily withdrawn from the U.S. market, it is still used in Asian countries. Evidence from epidemiological and animal studies indicate that decaBDE exposure targets brain development and produces behavioral impairments. The current study examined an array of motor and learning behaviors in a C57BL6/J mouse model to determine the breadth of the developmental neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood. Exposed male mice had impaired forelimb grip strength, altered motor output in a circadian wheel-running procedure, increased response errors during an operant differential reinforcement of low rates (DRL) procedure and a blunted response to an acute methylphenidate challenge administered before DRL testing. With the exception of altered wheel-running output, exposed females were not affected. Neither sex had altered somatic growth, motor coordination impairments on the Rotarod, gross learning deficits during operant lever-press acquisition, or impaired food motivation. The overall pattern of effects suggests that males are more sensitive to developmental decaBDE exposure, especially when performing behaviors that require effortful motor output or when learning tasks that require sufficient response inhibition for their successful completion. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Impaired inhibition and working memory in response to internet-related words among adolescents with internet addiction: A comparison with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Nie, Jia; Zhang, Wei; Chen, Jia; Li, Wendi

    2016-02-28

    Impairments in response inhibition and working memory functions have been found to be closely associated with internet addiction (IA) symptoms and attention-deficit/hyperactivity disorder (ADHD) symptoms. In this study, we examined response inhibition and working memory processes with two different materials (internet-related and internet-unrelated stimuli) among adolescents with IA, ADHD and co-morbid IA/ADHD. Twenty-four individuals with IA, 28 individuals with ADHD, 17 individuals with IA/ADHD, and 26 matched normal controls (NC) individuals were recruited. All participants were measured with a Stop-Signal Task and 2-Back Task under the same experimental conditions. In comparison to the NC group, subjects with IA, ADHD and IA/ADHD demonstrated impaired inhibition and working memory. In addition, in comparison to internet-unrelated conditions, IA and co-morbid subjects performed worse on the internet-related condition in the Stop trials during the stop-signal task, and they showed better working memory on the internet-related condition in the 2-Back Task. The findings of our study suggest individuals with IA and IA/ADHD may be impaired in inhibition and working memory functions that might be linked to poor inhibition specifically related to internet-related stimuli, which will advance our understanding of IA and contribute to prevention and intervention strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Hanford Facility contingency plan

    International Nuclear Information System (INIS)

    Sutton, L.N.; Miskho, A.G.; Brunke, R.C.

    1993-10-01

    The Hanford Facility Contingency Plan, together with each TSD unit-specific contingency plan, meets the WAC 173-303 requirements for a contingency plan. This plan includes descriptions of responses to a nonradiological hazardous materials spill or release at Hanford Facility locations not covered by TSD unit-specific contingency plans or building emergency plans. This plan includes descriptions of responses for spills or releases as a result of transportation activities, movement of materials, packaging, and storage of hazardous materials

  4. Experience from implementing international standards in national emergency response planning national adjustments and suggestions for improvements

    International Nuclear Information System (INIS)

    Naadland Holo, E.

    2003-01-01

    Full text: A process has been going on for some time in Norway to establish a harmonized background for emergency response planning for any kind of nuclear or radiological accident. The national emergency preparedness organisation with the crisis committee for nuclear accident, consisting of representatives from civil defence, defence, police-, health-, and food control authorities, has the authority to implement countermeasures to protect health, environment and national interests in case of an accident or in case of nuclear terrorism. However, in an early phase, the response plans need to be fully harmonized to ensure that every operational level knows their responsibility and the responsibilities of others. Our intention is to implement the IAEA standard 'preparedness and response for a nuclear or radiological emergency'. We believe this will simplify national and international communication and also simplify the crisis management if an accident occurs. In revising the national plans, and also the planning basis at regional and local level, as well as the planning basis for response to accidents at national nuclear facilities and in connection with arrival of nuclear submarines in Norwegian harbours, we have seen the need to make national adjustments to the international standards. In addition to the standard, there exist several other processes and routines for reporting different kinds of incidents. We have seen a need to coordinate this internally at the competent authority to simplify the routines. This paper will focus on the challenges we have met, our national solutions and some suggestions for simplification. National adjustments to the international standard. - Firstly, the threat categorization needs to be adjusted. First of all, we do not have nuclear power plants in Norway. In the aftermath of 11 September 2001 we also have focused more an the potential for nuclear terrorism. Nuclear terrorism is unlikely but puts up some new requirements in the

  5. Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Nam [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Dae Won [Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Kangneung 210-702 (Korea, Republic of); Jo, Hyo Sang; Shin, Min Jea; Ahn, Eun Hee; Ryu, Eun Ji; Yong, Ji In; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Youn, Jong Kyu; Hwang, Jae Hyeok [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeong, Ji-Heon; Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2015-07-15

    Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases. - Highlights: • Transduced Tat-CBR1 reduces LPS-induced inflammatory mediators and cytokines. • Tat-CBR1 inhibits MAPK and NF-κB activation. • Tat-CBR1 ameliorates inflammation response in vitro and in vivo. • Tat-CBR1 may be useful as potential therapeutic agent for inflammation.

  6. Integrating ecosystem services and climate change responses in coastal wetlands development plans for Bangladesh

    NARCIS (Netherlands)

    Sarwar, M.H.; Hein, L.G.; Rip, F.I.; Dearing, J.A.

    2015-01-01

    This study explores the integration of ecosystem services and climate change adaptation in development plans for coastal wetlands in Bangladesh. A new response framework for adaptation is proposed, based on an empirical analysis and consultations with stakeholders, using a modified version of the

  7. Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Amanda C Foks

    Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

  8. 33 CFR 154.1030 - General response plan contents.

    Science.gov (United States)

    2010-07-01

    ... and health plan. (vi) List of acronyms and definitions. (vii) A geographic-specific appendix for each... the National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (40 CFR part 300) and the Area Contingency Plan(s) (ACP) covering the area in which the facility operates. Facility owners or...

  9. Influence of inhibitory control on planning abilities in children with mild intellectual disability

    Directory of Open Access Journals (Sweden)

    Gligorović Milica

    2016-01-01

    Full Text Available With regard to the fact that the tendency toward unsophisticated strategies is often related to difficulties with basic components of executive functions, the aim of this research was to determine the relation between planning abilities and inhibitory control in children with mild intellectual disability (MID. The sample included 56 children with idiopathic MID (IQ 50-69, M=61.13, SD=7.14, of both genders (26/46.3% of girls, between 9.11 and 14.03 years of age (M=11.61; SD=1.29. Go no Go Task and Day/Night Stroop Task were used for the assessment of inhibitory control (delayed response to the agreed signal, conflict provoking motor responses, and inhibition of arrogant verbal responses, while Tower of London Test (ToL was used for the assessment of planning abilities. Multivariate analysis of covariance (MANCOVA, paired samples t-test, Pearson's correlation, and partial correlation coefficients were used in statistical analysis of the results. The results showed that the mistakes in Response delay set of Go-no-Go task were the only significant factor of primary Total move score variable (ToL. The influence of the ability to delay motor activity, assessed by Response delay set, on all ToL variables was statistically significant (p=0.003. The results lead to a conclusion that, during the processes of planning and executing activities, children with MID primarily rely on simple inhibitory mechanisms.

  10. Joint radiation emergency management plan of the international organizations. Emergency preparedness and response. Date effective: 1 January 2007

    International Nuclear Information System (INIS)

    2007-01-01

    binding treaties and have directives and regulations that bear on emergency response arrangements among some States. There are also bilateral agreements between some international organizations that also have relevance to preparedness and response arrangements. In March 2002, the IAEA issued Safety Requirements, entitled 'Preparedness and Response for a Nuclear or Radiological Emergency' (GS-R-2), jointly sponsored by the FAO, IAEA, the International Labour Organization (ILO), the OECD Nuclear Energy Agency (OECD/NEA), the United Nations Office for the Coordination of Humanitarian Affairs (OCHA), the Pan American Health Organization (PAHO) and WHO. These safety standards imply additional expectations with regard to operational emergency response arrangements. It is recognized by the participating organizations, and reflected in the above requirements, that good planning in advance of an emergency can substantially improve the response. With this in mind, the IAEA, the organizations party to the Conventions, and some other international organizations that participate in the activities of the IACRNA develop and maintain this 'Joint Radiation Emergency Management Plan of the International Organizations' (the Joint Plan), which describes: the objectives of response; the organizations involved in response, their roles and responsibilities, and the interfaces among them and between them and States; operational concepts; and preparedness arrangements. The various organizations reflect these arrangements in their own emergency plans. The IAEA is the main co-ordinating body for development and maintenance of the Joint Plan. All States irrespective whether they are party to one or other of the two Conventions are invited to adopt arrangements that are compatible with those described here when providing relevant information about nuclear or radiological emergencies to relevant international organizations, in order to minimize the radiological consequences and to facilitate the

  11. Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis inhibits both the initial adaptive and innate immune responses in mice.

    Science.gov (United States)

    Yang, Huiying; Wang, Tong; Tian, Guang; Zhang, Qingwen; Wu, Xiaohong; Xin, Youqian; Yan, Yanfeng; Tan, Yafang; Cao, Shiyang; Liu, Wanbing; Cui, Yujun; Yang, Ruifu; Du, Zongmin

    2017-01-01

    Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Culturally Responsive Education: Developing Lesson Plans for Vietnamese Students in the American Diaspora

    Science.gov (United States)

    Douglas, Cynthia M.

    2015-01-01

    This article focuses on the application of the philosophical principles of John Dewey and Culturally Responsive Education in the creation of lesson plans for Vietnamese students in the American Diaspora. Through a Fulbright-Hayes Program a group of teachers from the New York City Public School System and Long Island spent six weeks in Vietnam…

  13. Application of Wildfire Risk Assessment Results to Wildfire Response Planning in the Southern Sierra Nevada, California, USA

    Directory of Open Access Journals (Sweden)

    Matthew P. Thompson

    2016-03-01

    Full Text Available How wildfires are managed is a key determinant of long-term socioecological resiliency and the ability to live with fire. Safe and effective response to fire requires effective pre-fire planning, which is the main focus of this paper. We review general principles of effective federal fire management planning in the U.S., and introduce a framework for incident response planning consistent with these principles. We contextualize this framework in relation to a wildland fire management continuum based on federal fire management policy in the U.S. The framework leverages recent advancements in spatial wildfire risk assessment—notably the joint concepts of in situ risk and source risk—and integrates assessment results with additional geospatial information to develop and map strategic response zones. We operationalize this framework in a geographic information system (GIS environment based on landscape attributes relevant to fire operations, and define Potential wildland fire Operational Delineations (PODs as the spatial unit of analysis for strategic response. Using results from a recent risk assessment performed on several National Forests in the Southern Sierra Nevada area of California, USA, we illustrate how POD-level summaries of risk metrics can reduce uncertainty surrounding potential losses and benefits given large fire occurrence, and lend themselves naturally to design of fire and fuel management strategies. To conclude we identify gaps, limitations, and uncertainties, and prioritize future work to support safe and effective incident response.

  14. Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury

    Science.gov (United States)

    Coburn, Luke; Lopez, Hender; Schouwenaar, Irin-Maya; Yap, Alpha S.; Lobaskin, Vladimir; Gomez, Guillermo A.

    2018-03-01

    Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.

  15. Application of wildfire risk assessment results to wildfire response planning in the southern Sierra Nevada, California, USA

    Science.gov (United States)

    Matthew P. Thompson; Phil Bowden; April Brough; Joe H. Scott; Julie Gilbertson-Day; Alan Taylor; Jennifer Anderson; Jessica Haas

    2016-01-01

    How wildfires are managed is a key determinant of long-term socioecological resiliency and the ability to live with fire. Safe and effective response to fire requires effective pre-fire planning, which is the main focus of this paper. We review general principles of effective federal fire management planning in the U.S., and introduce a framework for incident...

  16. A substance P antagonist, [D-Pro2, D-Trp7,9]SP, inhibits inflammatory responses in the rabbit eye

    International Nuclear Information System (INIS)

    Holmdahl, G.; Hakanson, R.; Leander, S.; Rosell, S.; Folkers, K.; Sundler, F.

    1981-01-01

    Neurogenic factors released by antidromic nerve stimulation are thought to be in part responsible for the vasodilation and breakdown of the blood-aqueous barrier that follows trauma to the eye. Substance P is one candidate for the mediation of the inflammatory response since it is thought to be a neurotransmitter in sensory afferents and since exogenous substance P is capable of eliciting a response characteristic of inflammation. In rabbits, intravitreal or topical application onto the eye of a specific substance P antagonist, [d-Pro2, D-Trp7,9]SP, inhibited not only the irritant effects of exogenous substance P but also the inflammatory response to a standardized trauma (infrared irradiation of the iris). These observations suggest that substance P, or a related peptide, is a neurogenic mediator of the inflammatory response in the eye

  17. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis.

    Science.gov (United States)

    Kapina, Marina A; Rubakova, Elvira I; Majorov, Konstantin B; Logunova, Nadezhda N; Apt, Alexander S

    2013-01-01

    The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC) are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg), an essential element of a general immune regulatory network. However, direct experimental data demonstrating inhibition of immune responses by stroma-instructed immature DCreg in infectious models are scarce, and virtually nothing is known about functioning of this axis of immunity during tuberculosis (TB) infection. In this study, we demonstrate that lung stromal cells are capable of supporting the development in culture of immature CD11b(+)CD11c(low)CD103(-) DCreg from lineage-negative (lin(-)) bone marrow precursors. DCreg developed on lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and relatively resistant B6 inbred strains inhibited proliferative response of mycobacteria-specific CD4(+) T-cell lines a dose-dependent manner. Importantly, the inhibitory activity of B6 DCreg was substantially higher than that of I/St Dcreg. Moreover, when the donors of stromal cells were chronically infected with virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in B6, but further diminished in I/St stromal cells. DCreg-provided suppression was mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of CD4(+)Foxp3(+) Treg cells in the mediastinal, lung-draining lymph nodes at the advanced stages of chronic infection did not change in I/St, but increased 2-fold in B6 mice, and lung pathology was much more pronounced in the former mice. Taken together, these data provide genetic evidence that the capacity to maintain populations of regulatory cells

  18. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis.

    Directory of Open Access Journals (Sweden)

    Marina A Kapina

    Full Text Available The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg, an essential element of a general immune regulatory network. However, direct experimental data demonstrating inhibition of immune responses by stroma-instructed immature DCreg in infectious models are scarce, and virtually nothing is known about functioning of this axis of immunity during tuberculosis (TB infection. In this study, we demonstrate that lung stromal cells are capable of supporting the development in culture of immature CD11b(+CD11c(lowCD103(- DCreg from lineage-negative (lin(- bone marrow precursors. DCreg developed on lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and relatively resistant B6 inbred strains inhibited proliferative response of mycobacteria-specific CD4(+ T-cell lines a dose-dependent manner. Importantly, the inhibitory activity of B6 DCreg was substantially higher than that of I/St Dcreg. Moreover, when the donors of stromal cells were chronically infected with virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in B6, but further diminished in I/St stromal cells. DCreg-provided suppression was mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of CD4(+Foxp3(+ Treg cells in the mediastinal, lung-draining lymph nodes at the advanced stages of chronic infection did not change in I/St, but increased 2-fold in B6 mice, and lung pathology was much more pronounced in the former mice. Taken together, these data provide genetic evidence that the capacity to maintain populations of regulatory

  19. The national radiological emergency preparedness and response plan in the Philippines

    International Nuclear Information System (INIS)

    Valdezco, Eulinia Mendoza

    2007-01-01

    The use of radiation sources of various types and activities is now widespread in the fields of industry, medicine, research and education in the Philippines. These radiation sources have been under the regulatory control of the Philippine Nuclear Research Institute (PNRI) to ensure that these materials are used in a safe manner and stored in a safe and secure location, and that those which have exceeded their useful life are appropriately disposed of. And while the safety record of the nuclear industry remains admirable compared to other industries, the occurrence of an accident affecting members of the public is always a possibility but with very low probability. In 2001, the National Disaster Coordinating Council (NDCC) approved the revised National Radiological Emergency Preparedness and Response Plan (RADPLAN). This plan outlines the activities and organizations necessary to mitigate the effects of nuclear emergencies or radiation related accidents. An important component of this plan is the education of the public as well as the emergency responders such as the police authorities fire emergency personnel, medical responders, community leaders and the general public. The threat of nuclear terrorism as an aftermath of the September 11 incident in the United States has also been considered in the latest revision of this document. (author)

  20. Influenza pandemic planning guide

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-11-15

    An influenza pandemic will have serious economic impacts on the natural gas industry due to absenteeism as well as downstream effects due to supply disruption.This guide was prepared to assist gas distribution companies in planning for an influenza epidemic. The guide aimed to minimize the risks that an influenza pandemic might pose to the health and safety of employees and the continuity of business operations. The guide discussed 5 critical aspects of emergency planning: (1) prevention and threat mitigation; (2) preparedness; (3) response; (4) business continuity; and (5) communication. The legal context of the emergency plans were discussed. The plans were also discussed to other essential infrastructure emergency response plans. Recommendations were presented for infection control, decentralization and access restriction. Outlines for pandemic response planning teams and training and exercise programs were provided. Issues related to alert, mobilization, and response procedures were also discussed. 10 refs., 3 tabs., 1 fig.

  1. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Victoria Ryg-Cornejo

    2016-01-01

    Full Text Available Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.

  2. Predicting People's Environmental Behaviour: Theory of Planned Behaviour and Model of Responsible Environmental Behaviour

    Science.gov (United States)

    Chao, Yu-Long

    2012-01-01

    Using different measures of self-reported and other-reported environmental behaviour (EB), two important theoretical models explaining EB--Hines, Hungerford and Tomera's model of responsible environmental behaviour (REB) and Ajzen's theory of planned behaviour (TPB)--were compared regarding the fit between model and data, predictive ability,…

  3. Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons.

    Science.gov (United States)

    Borisyuk, Alla; Semple, Malcolm N; Rinzel, John

    2002-10-01

    A mathematical model was developed for exploring the sensitivity of low-frequency inferior colliculus (IC) neurons to interaural phase disparity (IPD). The formulation involves a firing-rate-type model that does not include spikes per se. The model IC neuron receives IPD-tuned excitatory and inhibitory inputs (viewed as the output of a collection of cells in the medial superior olive). The model cell possesses cellular properties of firing rate adaptation and postinhibitory rebound (PIR). The descriptions of these mechanisms are biophysically reasonable, but only semi-quantitative. We seek to explain within a minimal model the experimentally observed mismatch between responses to IPD stimuli delivered dynamically and those delivered statically (McAlpine et al. 2000; Spitzer and Semple 1993). The model reproduces many features of the responses to static IPD presentations, binaural beat, and partial range sweep stimuli. These features include differences in responses to a stimulus presented in static or dynamic context: sharper tuning and phase shifts in response to binaural beats, and hysteresis and "rise-from-nowhere" in response to partial range sweeps. Our results suggest that dynamic response features are due to the structure of inputs and the presence of firing rate adaptation and PIR mechanism in IC cells, but do not depend on a specific biophysical mechanism. We demonstrate how the model's various components contribute to shaping the observed phenomena. For example, adaptation, PIR, and transmission delay shape phase advances and delays in responses to binaural beats, adaptation and PIR shape hysteresis in different ranges of IPD, and tuned inhibition underlies asymmetry in dynamic tuning properties. We also suggest experiments to test our modeling predictions: in vitro simulation of the binaural beat (phase advance at low beat frequencies, its dependence on firing rate), in vivo partial range sweep experiments (dependence of the hysteresis curve on

  4. Kefir-isolated bacteria and yeasts inhibit Shigella flexneri invasion and modulate pro-inflammatory response on intestinal epithelial cells.

    Science.gov (United States)

    Bolla, P A; Abraham, A G; Pérez, P F; de Los Angeles Serradell, M

    2016-02-01

    The aim of this work was to evaluate the ability of a kefir-isolated microbial mixture containing three bacterial and two yeast strains (MM) to protect intestinal epithelial cells against Shigella flexneri invasion, as well as to analyse the effect on pro-inflammatory response elicited by this pathogen. A significant decrease in S. flexneri strain 72 invasion was observed on both HT-29 and Caco-2 cells pre-incubated with MM. Pre-incubation with the individual strains Saccharomyces cerevisiae CIDCA 8112 or Lactococcus lactis subsp. lactis CIDCA 8221 also reduced the internalisation of S. flexneri into HT-29 cells although in a lesser extent than MM. Interestingly, Lactobacillus plantarum CIDCA 83114 exerted a protective effect on the invasion of Caco-2 and HT-29 cells by S. flexneri. Regarding the pro-inflammatory response on HT-29 cells, S. flexneri infection induced a significant activation of the expression of interleukin 8 (IL-8), chemokine (C-C motif) ligand 20 (CCL20) and tumour necrosis factor alpha (TNF-α) encoding genes (P<0.05), whereas incubation of cells with MM did not induce the expression of any of the mediators assessed. Interestingly, pre-incubation of HT-29 monolayer with MM produced an inhibition of S. flexneri-induced IL-8, CCL20 and TNF-α mRNA expression. In order to gain insight on the effect of MM (or the individual strains) on this pro-inflammatory response, a series of experiments using a HT-29-NF-κB-hrGFP reporter system were performed. Pre-incubation of HT-29-NF-κB-hrGFP cells with MM significantly dampened Shigella-induced activation. Our results showed that the contribution of yeast strain Kluyveromyces marxianus CIDCA 8154 seems to be crucial in the observed effect. In conclusion, results presented in this study demonstrate that pre-treatment with a microbial mixture containing bacteria and yeasts isolated from kefir, resulted in inhibition of S. flexneri internalisation into human intestinal epithelial cells, along with the

  5. Homeland Security is Hometown Security: Comparison and Case Studies of Vertically Synchronized Catastrophe Response Plans

    Science.gov (United States)

    2015-09-01

    Hurricanes Andrew, Hugo , and Katrina resonate as failures where there was little, if any, federal response in the initial hours, which left the depleted...was also initiated by several large scale incidents, including the Three Mile Island Disaster and Hurricanes Hugo and Andrew.67 This evolved at the...persist during large scale disasters, as was demonstrated during Hurricane Katrina and Super Storm Sandy. Catastrophe response planning at the

  6. Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

    International Nuclear Information System (INIS)

    Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

    2003-01-01

    To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of γ-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of γ-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced γ-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression

  7. Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

    2003-11-27

    To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of {gamma}-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of {gamma}-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced {gamma}-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression.

  8. Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

    Science.gov (United States)

    Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

    2012-01-01

    The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

  9. Joint radiation emergency management plan of the international organizations. Emergency preparedness and response. Date effective: 1 December 2002

    International Nuclear Information System (INIS)

    2002-11-01

    directives and regulations that bear on emergency response arrangements among some States. There are also bilateral agreements between some international organizations that also have relevance to preparedness and response arrangements. In March 2002, the IAEA Board of Governors approved a Safety Requirements document to be issued according to the IAEA's statutory function 'to establish ... standards of safety for protection of health and minimization of danger to life and property'. These Safety Requirements, entitled 'Preparedness and Response for a Nuclear or Radiological Emergency' (GS-R-2), are being jointly sponsored by the FAO, IAEA, the International Labour Organisation (ILO), the OECD Nuclear Energy Agency (NEA/OECD), the United Nations Office for the Co-ordination of Humanitarian Affairs (OCHA), the Pan American Health Organization (PAHO) and WHO. These safety standards imply additional expectations with regard to operational emergency response arrangements. It has been recognized by the organizations responsible for emergency response, and reflected in the above requirements, that good planning in advance of an emergency can substantially improve the response. Moreover, one of the most important features of emergency response plans is to have clear lines of responsibility and authority. With this in mind, the IAEA, the organizations party to the Conventions, and some other international organizations that participate in the activities of the IACRNA develop and maintain this 'Joint Radiation Emergency Management Plan of the International Organizations' (the Joint Plan), which describes: the objectives of response; the organizations involved in response, their roles and responsibilities, and the interfaces among them and between them and States; operational concepts; and preparedness arrangements. These practical arrangements are reflected in the various organizations own emergency plans. The IAEA is the main co-ordinating body for development and maintenance of the

  10. Post-error response inhibition in high math-anxious individuals: Evidence from a multi-digit addition task.

    Science.gov (United States)

    Núñez-Peña, M Isabel; Tubau, Elisabet; Suárez-Pellicioni, Macarena

    2017-06-01

    The aim of the study was to investigate how high math-anxious (HMA) individuals react to errors in an arithmetic task. Twenty HMA and 19 low math-anxious (LMA) individuals were presented with a multi-digit addition verification task and were given response feedback. Post-error adjustment measures (response time and accuracy) were analyzed in order to study differences between groups when faced with errors in an arithmetical task. Results showed that both HMA and LMA individuals were slower to respond following an error than following a correct answer. However, post-error accuracy effects emerged only for the HMA group, showing that they were also less accurate after having committed an error than after giving the right answer. Importantly, these differences were observed only when individuals needed to repeat the same response given in the previous trial. These results suggest that, for HMA individuals, errors caused reactive inhibition of the erroneous response, facilitating performance if the next problem required the alternative response but hampering it if the response was the same. This stronger reaction to errors could be a factor contributing to the difficulties that HMA individuals experience in learning math and doing math tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Human β-defensin 3 inhibits periodontitis development by suppressing inflammatory responses in macrophages.

    Science.gov (United States)

    Cui, Di; Lyu, Jinglu; Li, Houxuan; Lei, Lang; Bian, Tianying; Li, Lili; Yan, Fuhua

    2017-11-01

    Human β-defensin 3 (hBD3) is a cationic peptide with immunomodulatory effects on both innate and acquired immune responses. Periodontitis, an inflammatory disease that extends deep into periodontal tissues, causes the loss of supporting structures around the tooth. The present study assessed the effects of hBD3 as a monotherapy for periodontitis in mice and explored its potential mechanism. In vivo, hBD3 inhibited the levels of tumour necrosis factor (TNF)-α, interleukin-6, and matrix metalloprotease-9 in periodontium exposed to Porphyromonas gingivalis (P.g) in a mouse periodontitis model; reduced osteoclast formation and lower alveolar bone loss were also observed. In addition, hBD3 was related to the expression of polarization signature molecules in circulating monocytes. In vitro, hBD3 notably suppressed the production of TNF-α and interleukin-6 in RAW 264.7 cells stimulated by the lipopolysaccharide of P.g. Moreover, hBD3 attenuated polarization of RAW 264.7 cells into the M1 phenotype, with reduced activation of nuclear factor-κB signal transduction. In conclusion, hBD3 exhibits potent anti-periodontitis properties both in vitro and in vivo, and this effect may be correlated to inhibition of the nuclear factor-κB pathway and macrophage polarization. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Science-based response planning guidance for the first 100 minutes of the response to a radiological dispersal device

    International Nuclear Information System (INIS)

    Musolino, S.V.; Harper, F.T.

    2016-01-01

    The first 100 minutes of a response to a radiological dispersal device are critical as this period will set the stage for how the overall response will be executed. First responders will be tasked with multiple activities such as confirming a radiological release, conducting lifesaving rescue operations, issuing protective actions, and beginning characterization of the scene. These activities need to take place as soon as the responders arrive on the scene (the first few minutes). The effectiveness of these early activities will define how well or how poorly the response will be in the emergency phase. The document which is under development provides guidance that can be used for planning an effective response to an RDD that will result in protection of the responders and the members of the public. The information is based on research and results of extensive experiments conducted by the Department of Energy National Laboratories. This guidance provides a realistic estimate of the possible consequences of an RDD detonation and delineates five missions and ten tactics that should be executed by the first responders and local response agencies in the first 100 minutes of a response. The guidance includes recommendations on how to execute the strategy, equipment requirements including personal protective equipment and public messaging

  13. Inhibition of Action, Thought, and Emotion: A Selective Neurobiological Review

    OpenAIRE

    Dillon, Daniel; Pizzagalli, Diego

    2007-01-01

    The neural bases of inhibitory function are reviewed, covering data from paradigms assessing inhibition of motor responses (antisaccade, go/nogo, stop-signal), cognitive sets (e.g., Wisconsin Card Sort Test), and emotion (fear extinction). The frontal cortex supports performance on these paradigms, but the specific neural circuitry varies: response inhibition depends upon fronto-basal ganglia networks, inhibition of cognitive sets is supported by orbitofrontal cortex, and retention of fear ex...

  14. Lower Colorado River Geographic Response Plan Web Mapping Service, Region 9, 2012, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — This map service is comprised of data related to Geographic Response Plans (GRPs) for the Lower Colorado River. Data layers were obtained from nationwide GIS...

  15. Tick saliva inhibits dendritic cell migration, maturation and function, while promoting development of Th2 responses

    Czech Academy of Sciences Publication Activity Database

    Skallová, Anna; Iezzi, G.; Ampenberger, F.; Kopf, M.; Kopecký, Jan

    2008-01-01

    Roč. 180, č. 9 (2008), s. 6186-9192 ISSN 0022-1767 R&D Projects: GA ČR GA524/05/0811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : dendritic cell * tick saliva * Th2 * immune responses Subject RIV: EC - Immunology Impact factor: 6.000, year: 2008

  16. 33 CFR 155.1050 - Response plan development and evaluation criteria for vessels carrying groups I through IV...

    Science.gov (United States)

    2010-07-01

    ... qualified individual; and (2) Within 30 minutes of a discovery of a discharge or substantial threat of... a discharge in advance of the arrival of response resources identified in the plan for tiers 1, 2... shoreline protection operations. (1) The response resources must include the quantities of boom listed in...

  17. Radiological Assistance Program, DOE Region 6 response plan

    International Nuclear Information System (INIS)

    Jakubowski, F.M.

    1993-02-01

    This program plan meets all the requirements identified in DOE Order 5530.3, Radiological Assistance Program and supports those requirements leading to the establishment of a Federal Radiological Monitoring and Assessment Center (FRMAC) as required by DOE 5530-5. Requests for radiological assistance may come from other DOE facilities, Federal or state agencies, tribal officials, or from any private corporation or individual. Many of the requests will be handled by a telephone call, a conference or a letter, teletype or memorandum. Other requests for assistance may involve radioactive material in serious accidents, fire, personal injuries, contamination or possible hazards to the general public. Some occurrences may require the dispatch of trained personnel equipped with radiation monitoring instruments and related equipment necessary to evaluate, control and neutralize the hazard. The primary responsibility for incidents involving radioactive material always remains with the party having custody of the radioactive materials. In addition, the DOE recognizes that the assistance provided shall not in any way preempt state, tribal, or local authority and/or responsibility on state or tribal properties. Toward this end, DOE assistance for non-DOE radioactive materials, is limited to technical assistance, advice, measurement and other resources as deemed necessary by the local authorities but excludes DOE interface with the public media. This is a function handled by the local or state Incident Commander

  18. Rainfall intensity-duration thresholds for postfire debris-flow emergency-response planning

    Science.gov (United States)

    Cannon, S.H.; Boldt, E.M.; Laber, J.L.; Kean, J.W.; Staley, D.M.

    2011-01-01

    Following wildfires, emergency-response and public-safety agencies can be faced with evacuation and resource-deployment decisions well in advance of coming winter storms and during storms themselves. Information critical to these decisions is provided for recently burned areas in the San Gabriel Mountains of southern California. A compilation of information on the hydrologic response to winter storms from recently burned areas in southern California steeplands is used to develop a system for classifying magnitudes of hydrologic response. The four-class system describes combinations of reported volumes of individual debris flows, consequences of debris flows and floods in an urban setting, and spatial extents of the hydrologic response. The range of rainfall conditions associated with different magnitude classes is defined by integrating local rainfall data with the response magnitude information. Magnitude I events can be expected when within-storm rainfall accumulations (A) of given durations (D) fall above the threshold A = 0.4D0.5 and below A = 0.5D0.6 for durations greater than 1 h. Magnitude II events will be generated in response to rainfall accumulations and durations between A = 0.4D0.5 and A = 0.9D0.5 for durations less than 1 h, and between A = 0.5D0.6 and A = 0.9D0.5 or durations greater than 1 h. Magnitude III events can be expected in response to rainfall conditions above the threshold A = 0.9D0.5. Rainfall threshold-magnitude relations are linked with potential emergency-response actions as an emergency-response decision chart, which leads a user through steps to determine potential event magnitudes and identify possible evacuation and resource-deployment levels. Use of this information in planning and response decision-making process could result in increased safety for both the public and emergency responders. ?? 2011 US Government.

  19. Nuclear emergency response planning based on participatory decision analytic approaches

    International Nuclear Information System (INIS)

    Sinkko, K.

    2004-10-01

    This work was undertaken in order to develop methods and techniques for evaluating systematically and comprehensively protective action strategies in the case of a nuclear or radiation emergency. This was done in a way that the concerns and issues of all key players related to decisions on protective actions could be aggregated into decision- making transparently and in an equal manner. An approach called facilitated workshop, based on the theory of Decision Analysis, was tailored and tested in the planning of actions to be taken. The work builds on case studies in which it was assumed that a hypothetical accident in a nuclear power plant had led to a release of considerable amounts of radionuclides and therefore different types of protective actions should be considered. Altogether six workshops were organised in which all key players were represented, i.e., the authorities, expert organisations, industry and agricultural producers. The participants were those responsible for preparing advice or presenting matters for those responsible for the formal decision-making. Many preparatory meetings were held with various experts to prepare information for the workshops. It was considered essential that the set-up strictly follow the decision- making process to which the key players are accustomed. Key players or stakeholders comprise responsible administrators and organisations, politicians as well as representatives of the citizens affected and other persons who will and are likely to take part in decision-making in nuclear emergencies. The realistic nature and the disciplined process of a facilitated workshop and commitment to decision-making yielded up insight in many radiation protection issues. The objectives and attributes which are considered in a decision on protective actions were discussed in many occasions and were defined for different accident scenario to come. In the workshops intervention levels were derived according justification and optimisation

  20. The Influence of Executive Functioning on Facial and Subjective Pain Responses in Older Adults

    Science.gov (United States)

    2016-01-01

    Cognitive decline is known to reduce reliability of subjective pain reports. Although facial expressions of pain are generally considered to be less affected by this decline, empirical support for this assumption is sparse. The present study therefore examined how cognitive functioning relates to facial expressions of pain and whether cognition acts as a moderator between nociceptive intensity and facial reactivity. Facial and subjective responses of 51 elderly participants to mechanical stimulation at three intensities levels (50 kPa, 200 kPa, and 400 kPa) were assessed. Moreover, participants completed a neuropsychological examination of executive functioning (planning, cognitive inhibition, and working memory), episodic memory, and psychomotor speed. The results showed that executive functioning has a unique relationship with facial reactivity at low pain intensity levels (200 kPa). Moreover, cognitive inhibition (but not other executive functions) moderated the effect of pressure intensity on facial pain expressions, suggesting that the relationship between pressure intensity and facial reactivity was less pronounced in participants with high levels of cognitive inhibition. A similar interaction effect was found for cognitive inhibition and subjective pain report. Consequently, caution is needed when interpreting facial (as well as subjective) pain responses in individuals with a high level of cognitive inhibition. PMID:27274618

  1. The role of right prefrontal and medial cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation.

    Science.gov (United States)

    Dambacher, Franziska; Sack, Alexander T; Lobbestael, Jill; Arntz, Arnoud; Brugmann, Suzanne; Schuhmann, Teresa

    2014-08-01

    The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint versus action cancellation. These two conceptually different aspects of action inhibition were measured with a go/no-go task (action restraint) and a stop signal task (action cancellation). Localization of relevant prefrontal activation was based on fMRI data. Significant task-related activation during successful action restraint was localized for each participant individually in right anterior insula (rAI), right superior frontal gyrus, and pre-SMA. Activation during successful action cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA. Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these regions. Results showed that the disruption of neural activity in rAI reduced both the ability to restrain (go/no-go) and cancel (stop signal) responses. In contrast, continuous thetaburst stimulation-induced disruption of the right superior frontal gyrus specifically impaired the ability to restrain from responding (go/no-go), while leaving the ability for action cancellation largely intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not affect inhibitory processing in neither of the two tasks. These findings provide a more comprehensive perspective on the role of pFC in inhibition and cognitive control. The results emphasize the role of inferior frontal regions for global inhibition, whereas superior frontal regions seem to be specifically relevant for successful action restraint.

  2. Oil spill response planning, training and facilities for wildlife in Prince William Sound, Alaska

    International Nuclear Information System (INIS)

    Hillman, S.O.

    1996-01-01

    The special provisions of the SERVS System of the Alyeska Pipeline Service Company concerning the treatment of wildlife in the event of an oil spill, were described. The Company is prepared to mobilize a rapid response for protection and treatment of wildlife in the event of an oil spill anywhere along the trans-Alaska pipeline or in Prince William Sound. Equipment for hazing, capture, and treatment is pre-assembled and staged at facilities at the Valdez Marine Terminal. Veterinarians and wildlife treatment specialists are under contract for treating oiled birds. This complex of wildlife response capabilities meets or exceeds the guidelines and response planning standards set by wildlife agencies. 7 refs., 6 figs

  3. Yampa River Valley sub-area contingency plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-08-01

    The Yampa River Valley sub-area contingency plan (Contingency Plan) has been prepared for two counties in northwestern Colorado: Moffat County and Routt County. The Contingency Plan is provided in two parts, the Contingency Plan and the Emergency Response Action Plan (ERAP). The Contingency Plan provides information that should be helpful in planning to minimize the impact of an oil spill or hazardous material incident. It contains discussions of planning and response role, hazards identification, vulnerability analysis, risk analysis, cleanup, cost recovery, training, and health and safety. It includes information on the incident command system, notifications, response capabilities, emergency response organizations, evacuation and shelter-in-place, and immediate actions.

  4. Impaired inhibition of prepotent motor actions in patients with Tourette syndrome

    NARCIS (Netherlands)

    Wylie, S.A.; Claassen, D.O.; Kanoff, K.E.; Ridderinkhof, K.R.; van den Wildenberg, W.P.M.

    2013-01-01

    Background: Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses

  5. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Science.gov (United States)

    Bunnell, Bryan E; Escobar, Jillian F; Bair, Kirsten L; Sutton, Mark D; Crane, John K

    2017-01-01

    Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  6. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Bryan E Bunnell

    Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  7. Williamsport Area Community College Long Range Planning: The Long Range Plan, Update 1987.

    Science.gov (United States)

    Williamsport Area Community Coll., PA.

    This update to Williamsport Area Community College's (WACC's) 1984-89 long-range plan offers a status report on each of the plan's 78 objectives, reassigns responsibility for specific objectives to make the plan responsive to the current organizational structure of the college, and offers 11 new objectives for the 1986-87 academic year. After…

  8. Intraglomerular inhibition shapes the strength and temporal structure of glomerular output.

    Science.gov (United States)

    Shao, Zuoyi; Puche, Adam C; Liu, Shaolin; Shipley, Michael T

    2012-08-01

    Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MCs) and external tufted cells (ETCs). ETCs, in turn, provide feedforward excitatory input to MCs. MC and ETCs are also regulated by inhibition: intraglomerular and interglomerular inhibitory circuits act at MC and ETC apical dendrites; granule cells (GCs) inhibit MC lateral dendrites via the MC→GC→MC circuit. We investigated the contribution of intraglomerular inhibition to MC and ETCs responses to ON input. ON input evokes initial excitation followed by early, strongly summating inhibitory postsynaptic currents (IPSCs) in MCs; this is followed by prolonged, intermittent IPSCs. The N-methyl-d-aspartate receptor antagonist dl-amino-5-phosphovaleric acid, known to suppress GABA release by GCs, reduced late IPSCs but had no effect on early IPSCs. In contrast, selective intraglomerular block of GABA(A) receptors eliminated all early IPSCs and caused a 5-fold increase in ON-evoked MC spiking and a 10-fold increase in response duration. ETCs also receive intraglomerular inhibition; blockade of inhibition doubled ETC spike responses. By reducing ETC excitatory drive and directly inhibiting MCs, intraglomerular inhibition is a key factor shaping the strength and temporal structure of MC responses to sensory input. Sensory input generates an intraglomerular excitation-inhibition sequence that limits MC spike output to a brief temporal window. Glomerular circuits may dynamically regulate this input-output window to optimize MC encoding across sniff-sampled inputs.

  9. Ethylene not responsible for inhibition of conidium germination by soils volatiles

    Energy Technology Data Exchange (ETDEWEB)

    Schippers, B.; Boerwinkel, D.J.; Konings, H.

    1978-01-01

    Volatile factors inhibiting the germination of Botrytis cinerea and Cochlibolus sativus conidia on membrane filters were emanated from six alkaline and two acid soils of different organic content and origin. Addition of lime or chitin increased the inhibitory action. Evidence is presented that ethylene is not involved either directly or indirectly in the inhibition of conidium germination above the different soils tested. 16 references, 4 figures, 2 tables.

  10. Statins inhibit protein lipidation and induce the unfolded protein response in the non-sterol producing nematode Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Mörck, Catarina; Elmelund-Præstekær, Louise Cathrine Braun; Kurth, Caroline

    2009-01-01

    of lipid moieties for protein prenylation. The nematode Caenorhabditis elegans possesses a mevalonate pathway that lacks the branch leading to cholesterol synthesis, and thus represents an ideal organism to specifically study the noncholesterol roles of the pathway. Inhibiting HMG-CoA reductase in C....... elegans using statins or RNAi leads to developmental arrest and loss of membrane association of a GFP-based prenylation reporter. The unfolded protein response (UPR) is also strongly activated, suggesting that impaired prenylation of small GTPases leads to the accumulation of unfolded proteins and ER...... and fatty acid composition were unaffected in statin-treated worms, even though they showed reduced staining with Nile red. We conclude that inhibitors of HMG-CoA reductase or of farnesyl transferases induce the UPR by inhibiting the prenylation of M57.2 substrates, resulting in developmental arrest in C...

  11. Functional brain correlates of motor response inhibition in children with developmental coordination disorder and attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Thornton, Siobhan; Bray, Signe; Langevin, Lisa Marie; Dewey, Deborah

    2018-06-01

    Motor impairment is associated with developmental coordination disorder (DCD), and to a lesser extent with attention-deficit/hyperactivity disorder (ADHD). Previous functional imaging studies investigated children with DCD or ADHD only; however, these two disorders co-occur in up to 50% of cases, suggesting that similar neural correlates are associated with these disorders. This study compared functional brain activation in children and adolescents (age range 8-17, M = 11.73, SD = 2.88) with DCD (n = 9), ADHD (n = 20), co-occurring DCD and ADHD (n = 18) and typically developing (TD) controls (n = 20). When compared to TD controls, children with co-occurring DCD/ADHD showed decreased activation during response inhibition in primary motor and sensory cortices. These findings suggest that children with co-occurring DCD and ADHD display significant functional changes in brain activation that could interfere with inhibition of erroneous motor responses. In contrast to previous studies, significant alterations in brain activation relative to TD controls, were not found in children with isolated DCD or ADHD. These findings highlight the importance of considering co-occurring disorders when investigating brain function in children with neurodevelopmental disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 11. Strategic planning.

    Science.gov (United States)

    2014-05-01

    There are several types of planning processes and plans, including strategic, operational, tactical, and contingency. For this document, operational planning includes tactical planning. This chapter examines the strategic planning process and includes an introduction into disaster response plans. "A strategic plan is an outline of steps designed with the goals of the entire organisation as a whole in mind, rather than with the goals of specific divisions or departments". Strategic planning includes all measures taken to provide a broad picture of what must be achieved and in which order, including how to organise a system capable of achieving the overall goals. Strategic planning often is done pre-event, based on previous experience and expertise. The strategic planning for disasters converts needs into a strategic plan of action. Strategic plans detail the goals that must be achieved. The process of converting needs into plans has been deconstructed into its components and includes consideration of: (1) disaster response plans; (2) interventions underway or planned; (3) available resources; (4) current status vs. pre-event status; (5) history and experience of the planners; and (6) access to the affected population. These factors are tempered by the local: (a) geography; (b) climate; (c) culture; (d) safety; and (e) practicality. The planning process consumes resources (costs). All plans must be adapted to the actual conditions--things never happen exactly as planned.

  13. Design basis of off-site emergency response plans for fuel cycle installations

    International Nuclear Information System (INIS)

    Rzepka, J.P.; Dubiau, Ph.; Jouve, A.C.; Charles, T.; Mercier, J.P.

    1995-01-01

    In France, the term 'off-site emergency response plan' refers to all the arrangements which should be made by the government authorities to protect the population in the event of an accident affecting the installations of the site considered. The outline of the method of defining typical accidents, evaluation of 'source-terms' and health consequences is presented. Two applications to installations from the front-end and from the back-end of the fuel cycle are discussed. (K.A.). 1 tab

  14. Piriformospora indica root colonization triggers local and systemic root responses and inhibits secondary colonization of distal roots.

    Science.gov (United States)

    Pedrotti, Lorenzo; Mueller, Martin J; Waller, Frank

    2013-01-01

    Piriformosporaindica is a basidiomycete fungus colonizing roots of a wide range of higher plants, including crop plants and the model plant Arabidopsis thaliana. Previous studies have shown that P. indica improves growth, and enhances systemic pathogen resistance in leaves of host plants. To investigate systemic effects within the root system, we established a hydroponic split-root cultivation system for Arabidopsis. Using quantitative real-time PCR, we show that initial P. indica colonization triggers a local, transient response of several defense-related transcripts, of which some were also induced in shoots and in distal, non-colonized roots of the same plant. Systemic effects on distal roots included the inhibition of secondary P. indica colonization. Faster and stronger induction of defense-related transcripts during secondary inoculation revealed that a P. indica pretreatment triggers root-wide priming of defense responses, which could cause the observed reduction of secondary colonization levels. Secondary P. indica colonization also induced defense responses in distant, already colonized parts of the root. Endophytic fungi therefore trigger a spatially specific response in directly colonized and in systemic root tissues of host plants.

  15. Planning deficits in polysubstance dependent users: Differential associations with severity of drug use and intelligence.

    Science.gov (United States)

    Valls-Serrano, C; Verdejo-García, A; Caracuel, A

    2016-05-01

    Polysubstance use is associated with alterations in different components of executive functioning such as working memory and response inhibition. Nevertheless, less attention has been given to executive planning skills, which are required to benefit of low structured interventions. This study examines the association between severity of use of cocaine, heroin, alcohol, fluid and crystallized intelligence and planning tasks varying on degree of structure. Data were collected from 60 polysubstance users and 30 healthy controls. Cognitive assessment consisted of three planning tasks with different structure levels: Stockings of Cambridge, Zoo Map test, and Multiple Errands Test. Polysubstance users had significant planning deficits across the three tasks compared to healthy controls. Hierarchical regression models showed that severity of drug use and fluid and crystallized intelligence significantly explained performance in all the planning tasks. However, these associations were higher for low-structured real world tasks. These low-structured tasks also showed a unique association with crystallized but not fluid intelligence. Drug abuse is negatively associated with planning abilities, and intelligence is positively associated with planning performance in real-world tasks. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

    Directory of Open Access Journals (Sweden)

    Bin Dai

    2017-01-01

    Full Text Available We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK, eukaryotic initiation factor 2-alpha (eIF2α and activating transcription factor 4 (ATF4. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

  17. Differences in functional activity between boys with pure oppositional defiant disorder and controls during a response inhibition task: a preliminary study.

    Science.gov (United States)

    Zhu, Yan; Ying, Kui; Wang, Ji; Su, Linyan; Chen, Jingyuan; Lin, Fan; Cai, Dongyang; Zhou, Ming; Wu, Daxing; Guo, Courtney; Wang, Shi

    2014-12-01

    Functional Magnetic Resonance Imaging (fMRI) of inhibitory control has only been investigated in patients with attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD). The objective of this study was to investigate the differences of functional areas associated with inhibitory control between boys with pure oppositional defiant disorder (ODD) and controls during a response inhibition task using functional magnetic resonance imaging (fMRI). Eleven boys with pure ODD and ten control boys, aged 10 to 12, performed a GoStop response inhibition task in this study. The task has a series of "go" trials to establish a pre-potent response tendency and a number of "stop" trials to test subjects' ability to withhold their responses. During the GoStop task, greater activation in the dorsolateral parts of the bilateral inferior frontal gyrus, left middle frontal gyrus (lMFG) and right superior frontal gyrus (rSFG) activation was seen in the ODD boys. Additionally, reduced activation in regions of the right inferior frontal gyrus (rIFG) was seen in the ODD boys in comparison with the control group. The results may suggest that the higher activation in areas adjacent to the rIFG could be the cause of reduced activation in the rIFG; although this is speculative and requires additional supporting evidence. The findings further suggest that ODD is a less pronounced functional disorder compared to ADHD and CD.

  18. Foreign Affairs: Specific Action Plan Needed to Improve Response to Parental Child Abductions

    Science.gov (United States)

    2000-03-01

    the child or prejudice to interested parties; (3) secure the voluntary return of the child or to bring about an amicable resolution of the issues, and...FOREIGN AFFAIRS Specific Action Plan Needed to Improve Response to Parental Child Abductions DISTRIBUTION STATEMENT A Approved for Public Release...International Parental Child Abduction 17 Page 1 GAO/NSIAD-00-10 Parental Child Abduction Page 2 GAO/NSIAD-00-10 Parental Child Abduction GAP

  19. A model national emergency plan for radiological accidents; Plan modelo nacional de respuesta de emergencia para accidentes radiologicos

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    The IAEA has supported several projects for the development of a national response plan for radiological emergencies. As a result, the IAEA has developed a model National Emergency Response Plan for Radiological Accidents (RAD PLAN), particularly for countries that have no nuclear power plants. This plan can be adapted for use by countries interested in developing their own national radiological emergency response plan, and the IAEA will supply the latest version of the RAD PLAN on computer diskette upon request.

  20. The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks.

    Science.gov (United States)

    Eagle, Dawn M; Bari, Andrea; Robbins, Trevor W

    2008-08-01

    The term 'action inhibition' encapsulates the ability to prevent any form of planned physical response. Growing evidence suggests that different 'stages' or even subtypes of action inhibition activate subtly different neuropharmacological and neuroanatomical processes. In this review, we present evidence from two commonly used and apparently similar behavioural tests, the stop-signal task and the go/no-go task, to determine if these have similar neuroanatomical and neurochemical modulation. Whilst performance of the stop-signal and go/no-go tasks is modulated across only subtly different anatomical networks, serotonin (5-HT) is strongly implicated in inhibitory control on the go/no-go but not the stop-signal task, whereas the stop-signal reaction time appears more sensitive to the action of noradrenaline. There is clear neuropharmacological and neuroanatomical evidence that stop-signal and go/no-go tasks represent different forms of action inhibition. This evidence translates with remarkable consistency across species. We discuss the possible implications of this evidence with respect to the development of novel therapeutic treatments for disorders in which inhibitory deficits are prominent and debilitating.

  1. DOE responses to Ecology review comments for ''Sampling and analysis plans for the 100-D Ponds voluntary remediation project''

    International Nuclear Information System (INIS)

    1996-01-01

    The Sampling and Analysis Plan describes the sampling and analytical activities which will be performed to support closure of the 100-D Ponds at the Hanford Reservation. This report contains responses by the US Department of Energy to Ecology review for ''Sampling and Analysis Plan for the 100-D Ponds Voluntary Remediation Project.''

  2. Lower Colorado River Geographic Response Plan Restricted Web Mapping Service, Region 9, 2012, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — This map service is comprised of data related to Geographic Response Plans (GRPs) for the Lower Colorado River. Data layers were contributed by various stakeholders...

  3. Physiological markers of motor inhibition during human behavior

    Science.gov (United States)

    Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B.

    2017-01-01

    Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. PMID:28341235

  4. Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition

    International Nuclear Information System (INIS)

    Blattmann, Claudia; Oertel, Susanne; Ehemann, Volker

    2010-01-01

    Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. Results: SAHA induced an inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.

  5. Contingency plans and successful response strategies for oil spills into rivers

    Energy Technology Data Exchange (ETDEWEB)

    Owens, Edward H. [Polaris Applied Sciences Inc., Bainbridge Island, WA (United States)]. E-mail: ehowens@polarisappliedsciences.com

    2003-07-01

    Oil spilled into a river enters a dynamic environment. An effective response can only succeed if the dynamics of the river system are understood and if the strategies and tactics are designed to match these conditions. Oil is transported downstream at the speed of the current, therefore, an estimate of the rate of movement is essential to identify effective intercept locations. Boom performance is affected by local surface water velocities as entrainment of oil typically begins when velocities exceed 0.4 m/s. However, boom configurations can be effective in current velocities as great as 2.5 m/s. Response operations can be successful if staging or control locations have been identified as part of contingency planning and if booms are deployed to take into account local surface current characteristics. Tracking and control of submerged or sunken oil is difficult and may not be practical. Recovery operations for sunken oil depend on the channel depth, current velocities, and on the distribution and concentration of the oil. (author)

  6. NSs protein of Schmallenberg virus counteracts the antiviral response of the cell by inhibiting its transcriptional machinery.

    Science.gov (United States)

    Barry, Gerald; Varela, Mariana; Ratinier, Maxime; Blomström, Anne-Lie; Caporale, Marco; Seehusen, Frauke; Hahn, Kerstin; Schnettler, Esther; Baumgärtner, Wolfgang; Kohl, Alain; Palmarini, Massimo

    2014-08-01

    Bunyaviruses have evolved a variety of strategies to counteract the antiviral defence systems of mammalian cells. Here we show that the NSs protein of Schmallenberg virus (SBV) induces the degradation of the RPB1 subunit of RNA polymerase II and consequently inhibits global cellular protein synthesis and the antiviral response. In addition, we show that the SBV NSs protein enhances apoptosis in vitro and possibly in vivo, suggesting that this protein could be involved in SBV pathogenesis in different ways. © 2014 The Authors.

  7. Direct contact between dendritic cells and bronchial epithelial cells inhibits T cell recall responses towards mite and pollen allergen extracts in vitro

    DEFF Research Database (Denmark)

    Papazian, Dick; Wagtmann, Valery R; Hansen, Soren

    2015-01-01

    (DCs), we have investigated recall T cell responses in allergic patients sensitized to house dust mite, grass, and birch pollen. Conclusions: Using allergen extract-loaded DCs to stimulate autologous allergen-specific T cell lines, we show that AEC-imprinted DCs inhibit T cell proliferation...... production of both Th1 and Th2 cytokines upon re-challenge. The inhibitory effects of AECs' contact with DCs were absent when allergen extract-loaded DCs had only been exposed to AECs supernatants, but present after direct contact with AECs. We conclude that direct contact between DCs and AECs inhibits T...

  8. Fear inhibition in high trait anxiety.

    Directory of Open Access Journals (Sweden)

    Merel Kindt

    Full Text Available Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders.

  9. Sable Offshore Energy Inc.: Response to 'The Canada-Nova Scotia Offshore Petroleum Board Benefits Plan Decision Report' Condition No. 3: Employment and Training Plan; Condition No. 4: Research and Development Plan; Condition No. 6: Disadvantaged Individual or Groups; Condition No. 7: Technology Transfer

    International Nuclear Information System (INIS)

    1998-01-01

    Decisions of the Canada-Nova Scotia Offshore Petroleum Board, regarding the responses of Sable Offshore Energy Inc (SOEI) to conditions imposed by the Board in the Sable Offshore Energy Project Canada-Nova Scotia Benefit Plan Decision Report, have been announced. According to the press release (copy attached), the Board accepted the responses of SOEI regarding the establishment and staffing of an office in Nova Scotia for the implementation and project management and training of project personnel, the level of expenditures for research and development to be undertaken in Nova Scotia, proposed initiatives for employment and training opportunities for disadvantaged individuals and groups, and a technology transfer plan that will facilitate succession planning and create joint venturing opportunities for Nova Scotian and Canadian industry. tabs., figs

  10. Estradiol-induced vaginal mucus inhibits antigen penetration and CD8(+) T cell priming in response to intravaginal immunization.

    Science.gov (United States)

    Seavey, Matthew M; Mosmann, Tim R

    2009-04-14

    Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8(+) T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APCs) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8(+) T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8(+) T cell priming after insemination or vaginal vaccination.

  11. Estradiol-induced vaginal mucus inhibits antigen penetration and CD8+ T cell priming in response to intravaginal immunization

    Science.gov (United States)

    Seavey, Matthew M.; Mosmann, Tim R.

    2010-01-01

    Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8+ T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APC) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8+ T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8+ T cell priming after insemination or vaginal vaccination. PMID:19428849

  12. What contributes to action plan enactment? Examining characteristics of physical activity plans.

    Science.gov (United States)

    Fleig, Lena; Gardner, Benjamin; Keller, Jan; Lippke, Sonia; Pomp, Sarah; Wiedemann, Amelie U

    2017-11-01

    Individuals with chronic conditions can benefit from formulating action plans to engage in regular physical activity. However, the content and the successful translation of plans into action, so-called plan enactment, are rarely adequately evaluated. The aim of this study was to describe the content of user-specified plans and to examine whether participants were more likely to enact their plans if these plans were highly specific, viable, and instrumental. The study presents secondary analyses from a larger behavioural intervention in cardiac and orthopaedic rehabilitation. The content of 619 action plans from 229 participants was evaluated by two independent raters (i.e., qualitative analyses and ratings of specificity) and by participants themselves (i.e., instrumentality and viability). Plan enactment was also measured via self-reports. Multilevel analyses examined the relationship between these plan characteristics and subsequent plan enactment, and between plan enactment and aggregated physical activity. Participants preferred to plan leisure-time physical activities anchored around time-based cues. Specificity of occasion cues (i.e., when to act) and highly instrumental plans were positively associated with plan enactment. Interestingly, individuals who planned less specific behavioural responses (i.e., what to do) were more likely to enact their plans. Plan enactment was positively associated with aggregated behaviour. Interventions should not only emphasize the importance of planning, but also the benefits of formulating specific contextual cues. Planning of the behavioural response seems to require less precision. Allowing for some flexibility in executing the anticipated target behaviour seems to aid successful plan enactment. Statement of Contribution What is already known on this subject? Action planning interventions are efficacious in promoting health behaviour. Characteristics of plan content (i.e., specificity) matter for unconditional behaviour

  13. Radiological emergency response planning: Handbook for Federal Assistance to State and Local Governments

    International Nuclear Information System (INIS)

    1978-12-01

    The handbook is directed toward those federal agencies involved in providing direct field assistance to state and local governments in radiological emergency response planning. Its principal purpose is to optimize the effectiveness of this effort by specifying the functions of the following federal agencies: Nuclear Regulatory Commission, Environmental Protection Agency, Department of Energy, Department of Health, Education, and Welfare, Department of Transportation, Defense Civil Preparedness Agency, Federal Disaster Assistance Administration, and Federal Preparedness Agency

  14. Response inhibition and measures of psychopathology: a dimensional analysis.

    NARCIS (Netherlands)

    Kooijmans, R.; Scheres, A.; Oosterlaan, J.

    2000-01-01

    On the basis of Quay's (1988a, 1988b, 1993, 1997) model in which the Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) are linked to various forms of child psychopathology, predictions were made regarding the relation between inhibitory control and two dimensions of

  15. Response inhibition and measures of psychopathology: A dimensional analysis

    NARCIS (Netherlands)

    Kooijmans, R.; Scheres, A.P.J.; Oosterlaan, J.

    2000-01-01

    On the basis of Quay's (1988a, 1988b, 1993, 1997) model in which the Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) are Linked to various forms of child psychopathology, predictions were made regarding the relation between inhibitory control and two dimensions of

  16. Remedial investigation plan for Waste Area Grouping 1 at Oak Ridge National Laboratory, Oak Ridge, Tennessee: Responses to regulator comments

    International Nuclear Information System (INIS)

    1991-05-01

    This document, ES/ER-6 ampersand D2, is a companion document to ORNL/RAP/Sub-87/99053/4 ampersand R1, Remedial Investigation Plan for ORNL Waste Area Grouping 1, dated August 1989. This document lists comments received from the Environmental Protection Agency, Region 4 (EPA) and the Tennessee Department of Health and Environment (TDHE) and responses to each of these comments. As requested by EPA, a revised Remedial Investigation (RI) Plan for Waste Area Grouping (WAG) 1 will not be submitted. The document is divided into two Sections and Appendix. Section I contains responses to comments issued on May 22, 1990, by EPA's Region 4 program office responsible for implementing the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Section 2 contains responses to comments issued on April 7, 1989, by EPA's program office responsible for implementing the Resource Conservation and Recovery Act (RCRA); these comments include issues raised by the TDHE. The Appendix contains the attachments referenced in a number of the responses. 35 refs

  17. Cortical organization of inhibition-related functions and modulation by psychopathology.

    Science.gov (United States)

    Warren, Stacie L; Crocker, Laura D; Spielberg, Jeffery M; Engels, Anna S; Banich, Marie T; Sutton, Bradley P; Miller, Gregory A; Heller, Wendy

    2013-01-01

    Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.

  18. Cortical organization of inhibition-related functions and modulation by psychopathology

    Directory of Open Access Journals (Sweden)

    Stacie L. Warren

    2013-06-01

    Full Text Available Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG and worry (BA10. Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.

  19. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

    Science.gov (United States)

    Bastos, Marcele F; Kayano, Ana Carolina A V; Silva-Filho, João Luiz; Dos-Santos, João Conrado K; Judice, Carla; Blanco, Yara C; Shryock, Nathaniel; Sercundes, Michelle K; Ortolan, Luana S; Francelin, Carolina; Leite, Juliana A; Oliveira, Rafaella; Elias, Rosa M; Câmara, Niels O S; Lopes, Stefanie C P; Albrecht, Letusa; Farias, Alessandro S; Vicente, Cristina P; Werneck, Claudio C; Giorgio, Selma; Verinaud, Liana; Epiphanio, Sabrina; Marinho, Claudio R F; Lalwani, Pritesh; Amino, Rogerio; Aliberti, Julio; Costa, Fabio T M

    2018-03-20

    Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen

  20. Licensee safeguards contingency plans

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The Nuclear Regulatory Commission is amending its regulations to require that licensees authorized to operate a nuclear reactor (other than certain research and test reactors), and those authorized to possess strategic quantities of plutonium, uranium-233, or uranium-235 develop and implement acceptable plans for responding to threats, thefts, and industrial sabotage of licensed nuclear materials and facilities. The plans will provide a structured, orderly, and timely response to safeguards contingencies and will be an important segment of NRC's contingency planning programs. Licensee safeguards contingency plans will result in organizing licensee's safeguards resources in such a way that, in the unlikely event of a safeguards contingency, the responding participants will be identified, their several responsibilities specified, and their responses coordinated