Adolescent social defeat decreases spatial working memory performance in adulthood.

PubMed

Novick, Andrew M; Miiller, Leah C; Forster, Gina L; Watt, Michael J

2013-10-17

Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.

40 CFR 86.1809-12 - Prohibition of defeat devices.

Code of Federal Regulations, 2014 CFR

2014-07-01

... manufacturer must provide an explanation containing detailed information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies..., with the Part II certification application, an engineering evaluation demonstrating to the satisfaction...

Adolescent Social Defeat Induced Alterations in Social Behavior and Cognitive Flexibility in Adult Mice: Effects of Developmental Stage and Social Condition

PubMed Central

Zhang, Fan; Yuan, Sanna; Shao, Feng; Wang, Weiwen

2016-01-01

Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using “resident-intruder” stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In Experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, postnatal days [PND] 28–37), late adolescence (LA, PND 38–47), and adulthood (ADULT, PND 70–79) and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST), were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning (RL) on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting (EDS) in adulthood but not during adolescence. In Experiment 2, we further examined the effects of social condition (isolation or social housing after stress) on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in Experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive function are differentially affected by the developmental stage and social condition. EA may comprise a particularly sensitive developmental period in which social defeat may produce a delayed impairment in cognitive flexibility during adulthood, and the social condition following stress appears to play an important intermediary role in the development of these cognitive deficits. PMID:27489540

40 CFR 86.1809-10 - Prohibition of defeat devices.

Code of Federal Regulations, 2012 CFR

2012-07-01

... detailed information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies incorporated for operation both during and... HLDT/MDPVs the manufacturer must submit, with the Part II certification application, an engineering...

Resveratrol as MDR reversion molecule in breast cancer: An overview.

PubMed

Alamolhodaei, Nafiseh Sadat; Tsatsakis, Aristidis M; Ramezani, Mohammad; Hayes, A Wallace; Karimi, Gholamreza

2017-05-01

Breast cancer is the most common cause of cancer mortality among women worldwide; therefore, a strategy to defeat breast cancer is an extremely important medical issue. One of the major challenges in this regard is multidrug resistance (MDR). Resveratrol, a well-known phytoestrogen, may be helpful as part of an overall strategy to defeat breast cancer. The mixed agonist and antagonist role of resveratrol for the estrogen receptor makes it a controversial but interesting molecule in cancer therapy, especially in hormone dependent cancers. Several in vitro investigations have suggested that resveratrol can reverse multidrug resistance. However, poor bioavailability of resveratrol is a potential limitation for resveratrol treatment and cancer outcome in vivo. Fortunately, combination therapy with other selected compounds improves resveratrol's bioavailability and/or a delay in its metabolism. This review summaries the available published literature dealing with the effects of resveratrol on multidrug resistance in cancer and more specifically, breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adolescent social defeat decreases spatial working memory performance in adulthood

PubMed Central

2013-01-01

Background Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Methods Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Results Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. Conclusions The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits. PMID:24134918

40 CFR 86.004-16 - Prohibition of defeat devices.

Code of Federal Regulations, 2012 CFR

2012-07-01

... information which the Administrator may request to be submitted) regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies...

40 CFR 86.004-16 - Prohibition of defeat devices.

Code of Federal Regulations, 2014 CFR

2014-07-01

... information which the Administrator may request to be submitted) regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies...

40 CFR 86.004-16 - Prohibition of defeat devices.

Code of Federal Regulations, 2013 CFR

2013-07-01

... information which the Administrator may request to be submitted) regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies...

How to Teach the Unteachable.

ERIC Educational Resources Information Center

Ciaccio, Joseph

1997-01-01

Describes a strategy of total positive response which aims to reverse the self-defeating cycle of punishment and failure in high-risk and troubled students. Details how to identify those students who are at risk, how to respond before misbehavior occurs, and the importance of finding something positive in all situations. (RJM)

Urine Scent Marking (USM): A Novel Test for Depressive-Like Behavior and a Predictor of Stress Resiliency in Mice

PubMed Central

Lehmann, Michael L.; Geddes, Claire E.; Lee, Jennifer L.; Herkenham, Miles

2013-01-01

Decreased interest in pleasurable stimuli including social withdrawal and reduced libido are some of the key symptomatic criteria for major depression, and thus assays that measure social and sexual behavior in rodents may be highly appropriate for modeling depressive states. Here we present a novel approach for validating rodent models of depression by assessing male urine scent marking (USM) made in consequence to a spot of urine from a proestrous female. USM is an ethologically important form of sexual communication expressed by males to attract females. The expression of this behavior is highly sensitive and adaptive to environmental cues and social status. We hypothesized that male USM behavior offers a naturalistic measure of social motivation that can be used to evaluate hedonic behaviors relevant to the study of mood disorders. We demonstrated that 1) adult male mice displayed a strong preference for marking proestrous female urine with a high degree of specificity, 2) exposure to chronic social defeat profoundly decreased USM whereas exposure to environmental enrichment increased USM, 3) the standard antidepressant fluoxetine reversed declines in USM induced by social defeat, 4) USM behavior closely correlated with other hedonic measures, and 5) USM scores in non-stressed mice predicted behavioral outcomes after defeat exposure such that mice displaying high preference for marking female urine prior to social defeat showed behavioral resiliency after social defeat. The findings indicate that the USM test is a sensitive, validated measure of psychosocial stress effects that has high predictive value for examination of stress resiliency and vulnerability and their neurobiological substrates. PMID:23875001

Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats.

PubMed

Sévoz-Couche, Caroline; Brouillard, Charly; Camus, Françoise; Laude, Dominique; De Boer, Sietse F; Becker, Chrystel; Benoliel, Jean-Jacques

2013-04-01

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders.

Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats

PubMed Central

Sévoz-Couche, Caroline; Brouillard, Charly; Camus, Françoise; Laude, Dominique; De Boer, Sietse F; Becker, Chrystel; Benoliel, Jean-Jacques

2013-01-01

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders. PMID:23297312

Antagonism of corticotropin-releasing factor CRF1 receptors blocks the enhanced response to cocaine after social stress.

PubMed

Ferrer-Pérez, Carmen; Reguilón, Marina D; Manzanedo, Carmen; Aguilar, M Asunción; Miñarro, José; Rodríguez-Arias, Marta

2018-03-15

Numerous studies have shown that social defeat stress induces an increase in the rewarding effects of cocaine. In this study we have investigated the role played by the main hypothalamic stress hormone, corticotropin-releasing factor (CRF), in the effects that repeated social defeat (RSD) induces in the conditioned rewarding effects and locomotor sensitization induced by cocaine. A total of 220 OF1 mice were divided into experimental groups according to the treatment received before each social defeat: saline, 5 or 10 mg/kg of the nonpeptidic corticotropin-releasing factor CRF 1 receptor antagonist CP-154,526, or 15 or 30 µg/kg of the peptidic corticotropin-releasing factor CRF 2 receptor antagonist Astressin 2 -B. Three weeks after the last defeat, conditioned place preference (CPP) induced by 1 mg/kg of cocaine was evaluated. Motor response to 10 mg/kg of cocaine was also studied after a sensitization induction. Blockade of corticotropin-releasing factor CRF 1 receptor reversed the increase in cocaine CPP induced by social defeat. Conversely, peripheral corticotropin-releasing factor CRF 2 receptor blockade produced similar effects to those observed in socially stressed animals. The effect of RSD on cocaine sensitization was again blocked by the corticotropin-releasing factor CRF 1 receptor antagonist, while peripheral CRF 2 receptor antagonist did not show effect. Acute administration of Astressin 2 -B induced an anxiogenic response. Our results confirm that CRF modulates the effects of social stress on reinforcement and sensitization induced by cocaine in contrasting ways. These findings highlight CRF receptors as potential therapeutic targets to be explored by research about stress-related addiction problems. Copyright © 2018 Elsevier B.V. All rights reserved.

Orexin signaling mediates the antidepressant-like effect of calorie restriction.

PubMed

Lutter, Michael; Krishnan, Vaishnav; Russo, Scott J; Jung, Saendy; McClung, Colleen A; Nestler, Eric J

2008-03-19

During periods of reduced food availability, animals must respond with behavioral adaptations that promote survival. Despite the fact that many psychiatric syndromes include disordered eating patterns as a component of the illness, little is known about the neurobiology underlying behavioral changes induced by short-term calorie restriction. Presently, we demonstrate that 10 d of calorie restriction, corresponding to a 20-25% weight loss, causes a marked antidepressant-like response in two rodent models of depression and that this response is dependent on the hypothalamic neuropeptide orexin (hypocretin). Wild-type mice, but not mice lacking orexin, show longer latency to immobility and less total immobility in the forced swim test after calorie restriction. In the social defeat model of chronic stress, calorie restriction reverses the behavioral deficits seen in wild-type mice but not in orexin knock-out mice. Additionally, chronic social defeat stress induces a prolonged reduction in the expression of prepro-orexin mRNA via epigenetic modification of the orexin gene promoter, whereas calorie restriction enhances the activation of orexin cells after social defeat. Together, these data indicate that orexin plays an essential role in mediating reduced depression-like symptoms induced by calorie restriction.

2006 Joint Chemical Biological, Radiological and Nuclear (CBRN) Conference and Exhibition

DTIC Science & Technology

2006-06-28

methods that might counter or cancel our current military advantages • Defeat terrorist networks • Defend homeland in depth • Prevent acquisition or...Systems approach to the detection of chemical and biological agents with a focus on genetically engineered organisms ( GMOs )/genetically engineered...and possessing breakthrough technological capabilities intended to supplant U.S. advantages in particular operational domains. (capsize our power

Amended Complaint for Volkswagen

EPA Pesticide Factsheets

The settlement partially resolves allegations that Volkswagen violated the Clean Air Act (“CAA”) by the sale of approximately 500,000 model year 2009 to 2015 motor vehicles containing 2.0 liter diesel engines equipped with “defeat devices” (“CAA 2.0 liter.

Reversible brazing process

DOEpatents

Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

1999-01-01

A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

40 CFR 86.1809-01 - Prohibition of defeat devices.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... emission control, the Administrator will use a guideline to determine the appropriateness of the CO...

40 CFR 86.1809-12 - Prohibition of defeat devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... device. (c) For cold temperature CO and cold temperature NMHC emission control, the Administrator will...

40 CFR 86.1809-10 - Prohibition of defeat devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... device. (c) For cold temperature CO and cold temperature NMHC emission control, the Administrator will...

40 CFR 86.1809-01 - Prohibition of defeat devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... emission control, the Administrator will use a guideline to determine the appropriateness of the CO...

40 CFR 86.1809-01 - Prohibition of defeat devices.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... emission control, the Administrator will use a guideline to determine the appropriateness of the CO...

40 CFR 86.1809-12 - Prohibition of defeat devices.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... device. (c) For cold temperature CO and cold temperature NMHC emission control, the Administrator will...

40 CFR 86.1809-10 - Prohibition of defeat devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... device. (c) For cold temperature CO and cold temperature NMHC emission control, the Administrator will...

40 CFR 86.1809-01 - Prohibition of defeat devices.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light-Duty Trucks... control, the Administrator will use a guideline to determine the appropriateness of the CO emission...

40 CFR 86.1809-10 - Prohibition of defeat devices.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... device. (c) For cold temperature CO and cold temperature NMHC emission control, the Administrator will...

40 CFR 86.1809-01 - Prohibition of defeat devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... emission control, the Administrator will use a guideline to determine the appropriateness of the CO...

40 CFR 86.1809-12 - Prohibition of defeat devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air Pollution From New and In-Use Light-Duty Vehicles, Light... device. (c) For cold temperature CO and cold temperature NMHC emission control, the Administrator will...

40 CFR 86.094-16 - Prohibition of defeat devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Provisions for Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles, Light-Duty Trucks and Heavy-Duty Engines, and for 1985 and Later Model Year New Gasoline Fueled, Natural Gas-Fueled... congruity across the intermediate temperature range is the linear interpolation between the CO standard...

Expedient Gap Definition Using 3D LADAR

DTIC Science & Technology

2006-09-01

Research and Development Center (ERDC), ASI has developed an algorithm to reduce the 3D point cloud acquired with the LADAR system into sets of 2D...ATO IV.GC.2004.02. The GAP Program is conducted by the U.S. Army Engineer Research and Development Center (ERDC) in conjunction with the U.S. Army...Introduction 1 1 Introduction Background The Battlespace Gap Definition and Defeat ( GAP ) Program is conducted by the U.S. Army Engineer Research and

Consequences of continuous social defeat stress on anxiety- and depressive-like behaviors and ethanol reward in mice.

PubMed

Macedo, Giovana Camila; Morita, Gleice Midori; Domingues, Liz Paola; Favoretto, Cristiane Aparecida; Suchecki, Deborah; Quadros, Isabel Marian Hartmann

2018-01-01

This study employed the intruder-resident paradigm to evaluate the effects of continuous social defeat on depressive- and anxiety-like behaviors and the reinforcing and motivational actions of ethanol in male Swiss mice. Male Swiss mice were exposed to a 10-day social defeat protocol, while control mice cohabitated with a non-aggressive animal. Continuous defeat stress consisted of episodes of defeat, followed by 24h or 48h cohabitation with the aggressor until the following defeat. Mice were assessed for sucrose drinking (anhedonia), social investigation test, elevated plus-maze, conditioned place preference to ethanol, and locomotor response to ethanol. Plasma corticosterone was measured prior to, after the first and the final defeat, and 10days after the end of defeat. Defeated mice exhibited a depressive-like phenotype as indicated by social inhibition and reduced sucrose preference, relative to non-defeated controls. Defeated mice also displayed anxiety-like behavior when tested in the elevated plus-maze. Stressed animals failed to present ethanol-induced locomotor stimulation, but showed increased sensitivity for ethanol-induced conditioned place preference. Corticosterone response to defeat was the highest after the first defeat, but was still elevated after the last defeat (day 10) when compared to non-stressed controls. Baseline corticosterone levels were unchanged 10days after the final defeat. These data suggest that social defeat stress increased depressive- and anxiety-like behavior as well increased vulnerability to ethanol reward in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

The Unauthorized Movement of Nuclear Weapons and Mistaken Shipment of Classified Missile Components: An Assessment

DTIC Science & Technology

2012-01-01

options to defeat any aggressor .44 The 2002 National Security Strategy further articulated the Administration‘s focus on WMD. It is this change...Review that reduced the role of U.S. nuclear weapons to largely, but not completely, a retaliatory role against any nuclear aggressor , reversing the...the Air Force‘s nuclear cognitive -dissonance that interviewees relayed to the Study Team. In addition to addressing joint operations, Goldwater

Third Partial and 3.0L Second Partial and 2.0L Partial and Amended Consent Decree

EPA Pesticide Factsheets

The settlement partially resolves allegations that Volkswagen violated the Clean Air Act (“CAA”) by the sale of approximately 500,000 model year 2009 to 2015 motor vehicles containing 2.0 liter diesel engines equipped with “defeat devices” (“CAA 2.0 liter.

Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice.

PubMed

Bondar, Natalya; Bryzgalov, Leonid; Ershov, Nikita; Gusev, Fedor; Reshetnikov, Vasiliy; Avgustinovich, Damira; Tenditnik, Mikhail; Rogaev, Evgeny; Merkulova, Tatiana

2018-04-01

Chronic stress is a risk factor for major depression. Social defeat stress is a well-validated murine model of depression. However, little is known about the gene activity dynamics during the development of a depression-like state. We analyzed the effects of social defeat stress of varying duration (10 and 30 days) on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice. The 10-day exposure to social defeat stress resulted in a high level of social avoidance with no signs of depression-associated behavior. Most animals exposed to 30 days of social defeat stress demonstrated clear hallmarks of depression, including a higher level of social avoidance, increased immobility in the forced swimming test, and anhedonic behavior. The monitoring of transcriptome changes revealed widespread alterations in gene expression on the 10th day. Surprisingly, the expression of only a few genes were affected by the 30th day of stress, apparently due to a reversal of the majority of the early stress-induced changes to the original basal state. Moreover, we have found that glucocorticoid-sensitive genes are clearly stimulated targets on the 10th day of stress, but these genes stop responding to the elevated corticosterone level by the 30th day of stress. The majority of genes altered by the 30-day stress were downregulated, with the most relevant ones participating in chromatin modifications and neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of GTPases). Very different molecular responses occur during short-term and long-term social stress in mice. The early-stress response is associated with social avoidance and with upregulation and downregulation of many genes, including those related to signal transduction and cell adhesion pathways. Downregulation of a few genes, in particular, genes for histone-modifying methyltransferases, is a signature response to prolonged stress that induces symptoms of depression. Altogether, our data show that the development of depression under social stress conditions is correlated with suppression of the overactive molecular response to induced stress, involving gene regulatory resistance to glucocorticoid molecules, potentially via a chromatin remodeling mechanism.

An Aversion to Risk; A Warning from the Past

DTIC Science & Technology

2014-06-02

Macmillan, 2010), 79, accessed August 27, 2013, http://web.ebscohost.com/ehost/ebookviewr/ ebook /nlebk328583AN?sid"Ŝc887269-f5dc-46b0-887e· ed5222a43afe...McDowell’s defeated army in November 1861. McClellan quickly reversed the army’s poor morale through applications of discipline, organization, training...politicians.30 The ignoble civilian-military issues that swirled through the Mexican War Theater also influenced McClellan. During the Mexican War

Panacea or Perestroika: A Socio-Economic Analysis of the Equity and Efficiency Effects of Choice in Education

DTIC Science & Technology

1991-12-01

better educational resources. Schools cannot be expected to win The War on Poverty, to defeat drugs, racism and sexism , when the school is but a...Equal Education Opportunity, Human Capital Theory 19 Ah$TPACT Continue on reverse if necessary and identify by block number) This paper looks at the ...attainments at the primary and secondary level is obvious. The measures used by the National Center for Education Statistics to deter- mine the efficacy

Pressure for a select committee on human embryo research and genetic engineering.

PubMed

McKie, David

1985-11-02

By a commanding majority of almost five million votes, this year's Labour Party conference agreed that Labour Members of Parliament should not be permitted to let their consciences decide their votes on "issues affecting the reproductive rights of women." The targets for this censure were the 44 Labour MPs who backed Enoch Powell's bill to outlaw experiments on embryos. Conservative supporters of the Powell bill are countering their defeat by advocating a Parliamentary select committee to examine "matters of human embryo research and human genetic engineering." McKie comments that they are thus shifting emphasis from "fertility," which has public support, to genetic engineering, which generates fear.

Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: Role of social experience and adaptive coping behavior

PubMed Central

Burke, Andrew R.; Miczek, Klaus A.

2015-01-01

Background The link between adolescent social stress and substance abuse is modeled in social defeat of adolescent male rats, at an age when social experiences are essential for neurobehavioral maturation. Objective We investigated the role of social experience and social defeat stress during adolescence on social behavior and cocaine self administration (CocSelfAd) in early adulthood. Methods We manipulated social experience by housing male rats in pairs (PH) or singly (SH) on postnatal day (P) 21. In addition, rats were subjected to social defeat from P35-44. Social behavior was measured during the first and last social defeat in PH and SH adolescents and PH adults. After assessing the behavioral response to novelty and cocaine (P57-61), intra-jugular catheters were implanted and CocSelfAd was analyzed. Results Residents were less aggressive toward PH adolescent intruders compared to PH adult intruders. Adults were submissive and defensive when attacked, whereas PH adolescents froze. In the course of repeated defeats, adolescent PH rats increased freezing, while SH rats decreased freezing. Longer attack-induced freezing after repeated defeats predicted escalated CocSelfAd in adulthood. PH controls acquired CocSelfAd more slowly than PH defeated and SH rats. Defeated PH rats increased CocSelfAd during progressive ratio schedules of reinforcement and during a 24-hour continuous access binge compared to PH controls and SH defeated rats. Conclusions Social defeat in adolescence of PH rats caused persistent increases in adult CocSelfAd. Adolescent PH rats coped with attacks adaptively by increasing freezing behavior after repeated social defeats, a measure that predicted CocSelfAd in adulthood. PMID:25943168

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice.

PubMed

Ito, Naoki; Hirose, Eiji; Ishida, Tatsuya; Hori, Atsushi; Nagai, Takayuki; Kobayashi, Yoshinori; Kiyohara, Hiroaki; Oikawa, Tetsuro; Hanawa, Toshihiko; Odaguchi, Hiroshi

2017-05-03

Kososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS. In the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1-10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1-12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13-15. Oral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment. Our findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.

Repeated, Intermittent Social Defeat across the Entire Juvenile Period Resulted in Behavioral, Physiological, Hormonal, Immunological, and Neurochemical Alterations in Young Adult Male Golden Hamsters

PubMed Central

Yu, Wei-Chun; Liu, Ching-Yi; Lai, Wen-Sung

2016-01-01

The developing brain is vulnerable to social defeat during the juvenile period. As complements of human studies, animal models of social defeat provide a straightforward approach to investigating the functional and neurobiological consequences of social defeats. Taking advantage of agonist behavior and social defeat in male golden hamster, a set of 6 experiments was conducted to investigate the consequences at multiple levels in young adulthood resulting from repeated, intermittent social defeats or “social threats” across the entire juvenile period. Male hamsters at postnatal day 28 (P28) were randomly assigned to either the social defeat, “social threat”, or arena control group, and they correspondingly received a series of nine social interaction trials (i.e., either social defeat, “social threat”, or arena control conditions) from P33 to P66. At the behavioral level (Experiment 1), we found that repeated social defeats (but not “social threats”) significantly impacted locomotor activity in the familiar context and social interaction in the familiar/unfamiliar social contexts. At the physiological and hormonal levels (Experiments 2 and 3), repeated social defeat significantly enhanced the cortisol and norepinephrine concentrations in blood. Enlargement of the spleen was also found in the social defeat and “social threat” groups. At the immunological level (Experiment 4), the social defeat group showed lower levels of pro-inflammatory cytokines in the hypothalamus and hippocampus but higher concentration of IL-6 in the striatum compared to the other two groups. At the neurochemical level (Experiment 5), the socially defeated hamsters mainly displayed reductions of dopamine, dopamine metabolites, and 5-HT levels in the striatum and decreased level of 5-HT in the hippocampus. In Experiment 6, an increase in the spine density of hippocampal CA1 pyramidal neurons was specifically observed in the “social threat” group. Collectively, our findings indicate that repeated, intermittent social defeats throughout entire adolescence in hamsters impact their adult responses at multiple levels. Our results also suggest that the “social threat” group may serve as an appropriate control. This study further suggest that the alterations of behavioral responses and neurobiological functions in the body and brain might provide potential markers to measure the negative consequences of chronic social defeats. PMID:27375450

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

PubMed

Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

2014-05-01

Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice

PubMed Central

Iñiguez, Sergio D.; Riggs, Lace M.; Nieto, Steven J.; Dayrit, Genesis; Zamora, Norma N.; Shawhan, Kristi L.; Cruz, Bryan; Warren, Brandon L.

2016-01-01

Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35–44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7–12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence. PMID:24689732

Testing a Conceptual Model of Working through Self-Defeating Patterns

ERIC Educational Resources Information Center

Wei, Meifen; Ku, Tsun-Yao

2007-01-01

The present study developed and examined a conceptual model of working through self-defeating patterns. Participants were 390 college students at a large midwestern university. Results indicated that self-defeating patterns mediated the relations between attachment and distress. Also, self-esteem mediated the link between self-defeating patterns…

Correlations between self-handicapping and self-defeating personality.

PubMed

Schill, T; Morales, J; Beyler, J; Tatter, T; Swigert, L

1991-10-01

In this study scores on Strube's self-handicapping scale were correlated with scores on Schill's self-defeating personality scale. Berglas believes there are subtypes of self-defeating personality and that his concept of self-handicapping should be correlated with the three criteria which represent a self-protective component of self-defeating personality. Some support for Berglas' proposition was found, particularly for men. However, correlations with other components of self-defeating personality suggest the criteria thought to be self-protective may need to be reconsidered.

Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory.

PubMed

Eacret, Darrell; Grafe, Laura A; Dobkin, Jane; Gotter, Anthony L; Rengerb, John J; Winrow, Christopher J; Bhatnagar, Seema

2018-06-11

Orexins are neuropeptides synthesized in the lateral hypothalamus that influence arousal, feeding, reward pathways, and the response to stress. However, the role of orexins in repeated stress is not fully characterized. Here, we examined how orexins and their receptors contribute to the coping response during repeated social defeat and subsequent anxiety-like and memory-related behaviors. Specifically, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to stimulate orexins prior to each of five consecutive days of social defeat stress in adult male rats. Additionally, we determined the role of the orexin 2 receptor in these behaviors by using a selective orexin 2 receptor antagonist (MK-1064) administered prior to each social defeat. Following the 5 day social defeat conditioning period, rats were evaluated in social interaction and novel object recognition paradigms to assess anxiety-like behavior and recognition memory, respectively. Activation of orexin neurons by DREADDs prior to each social defeat decreased the average latency to become defeated across 5 days, indicative of a passive coping strategy that we have previously linked to a stress vulnerable phenotype. Moreover, stimulation of orexin signaling during defeat conditioning decreased subsequent social interaction and performance in the novel object recognition test indicating increased subsequent anxiety-like behavior and reduced working memory. Blocking the orexin 2 receptor during repeated defeat did not alter these effects. Together, our results suggest that orexin neuron activation produces a passive coping phenotype during social defeat leading to subsequent anxiety-like behaviors and memory deficits. Copyright © 2018. Published by Elsevier B.V.

Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice.

PubMed

Nasanbuyan, Naranbat; Yoshida, Masahide; Takayanagi, Yuki; Inutsuka, Ayumu; Nishimori, Katsuhiko; Yamanaka, Akihiro; Onaka, Tatsushi

2018-02-01

Social stress has deteriorating effects on various psychiatric diseases. In animal models, exposure to socially dominant conspecifics (i.e., social defeat stress) evokes a species-specific defeat posture via unknown mechanisms. Oxytocin neurons have been shown to be activated by stressful stimuli and to have prosocial and anxiolytic actions. The roles of oxytocin during social defeat stress remain unclear. Expression of c-Fos, a marker of neuronal activation, in oxytocin neurons and in oxytocin receptor‒expressing neurons was investigated in mice. The projection of oxytocin neurons was examined with an anterograde viral tracer, which induces selective expression of membrane-targeted palmitoylated green fluorescent protein in oxytocin neurons. Defensive behaviors during double exposure to social defeat stress in oxytocin receptor‒deficient mice were analyzed. After social defeat stress, expression of c-Fos protein was increased in oxytocin neurons of the bed nucleus of the stria terminalis, supraoptic nucleus, and paraventricular hypothalamic nucleus. Expression of c-Fos protein was also increased in oxytocin receptor‒expressing neurons of brain regions, including the ventrolateral part of the ventromedial hypothalamus and ventrolateral periaqueductal gray. Projecting fibers from paraventricular hypothalamic oxytocin neurons were found in the ventrolateral part of the ventromedial hypothalamus and in the ventrolateral periaqueductal gray. Oxytocin receptor‒deficient mice showed reduced defeat posture during the second social defeat stress. These findings suggest that social defeat stress activates oxytocin-oxytocin receptor systems, and the findings are consistent with the view that activation of the oxytocin receptor in brain regions, including the ventrolateral part of the ventromedial hypothalamus and the ventrolateral periaqueductal gray, facilitates social defeat posture.

Repeated social defeat-induced neuroinflammation, anxiety-like behavior and resistance to fear extinction were attenuated by the cannabinoid receptor agonist WIN55,212-2.

PubMed

Lisboa, Sabrina Francesca; Niraula, Anzela; Resstel, Leonardo Barbosa; Guimaraes, Francisco Silveira; Godbout, Jonathan P; Sheridan, John F

2018-04-17

Psychosocial stress contributes to the development of psychiatric disorders. Repeated social defeat (RSD) is a murine stressor that causes a release of inflammatory monocytes into circulation. Moreover, RSD-induced anxiety-like behavior is dependent on the recruitment of these monocytes to the brain. Activation of the endocannabinoid (ECB) system may modulate both neuroendocrine and inflammatory responses mediated by stress. Therefore, we hypothesized that a cannabinoid receptor agonist would attenuate RSD-induced inflammation, anxiety, and stress sensitization. To test this hypothesis, mice received an injection of the synthetic cannabinoid 1/2 receptor agonist, WIN55,212-2 (WIN; 1 mg/kg, intraperitoneally) daily for six consecutive days, 30 min before each exposure to RSD. Anxiety-like behavior, immune activation, neuroinflammation, and microglial reactivity were determined 14 h after RSD. RSD-induced anxiety-like behavior in the open field and in the EPM was reversed by WIN55,212-2. Moreover, WIN55,212-2 reduced the accumulation of inflammatory monocytes in circulation and brain after RSD and attenuated RSD-induced interleukin-1β (IL-1β) messenger RNA (mRNA) expression in microglia/macrophages. Increased ex vivo reactivity of microglia/monocytes to lipopolysaccharides (LPS) after RSD was also attenuated by WIN55,212-2. Next, fear expression, extinction, and recall were evaluated 24 and 48 h, respectively, after contextual fear conditioning, which took place 7 days after RSD. Here, RSD caused prolonged fear expression and impaired fear extinction recall, which was associated with increased IL-1β mRNA in the brain. Moreover, these stress-induced effects were reversed by WIN55,212-2. In conclusion, activation of cannabinoid receptors limited the immune and neuroinflammatory responses to RSD and reversed the short-term and long-term behavioral deficits associated with RSD.

Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice.

PubMed

García-Pardo, Maria P; Rodríguez-Arias, Marta; Maldonado, Concepcion; Manzanedo, Carmen; Miñarro, Jose; Aguilar, Maria A

2014-09-01

Exposure to social defeat stress increases the rewarding effects of psychostimulants in animal models, but its effect on 3,4-methylenedioxymethylamphetamine (MDMA) reward has received little attention. In the present study, we evaluated the influence of social defeat on the rewarding effects of MDMA in adolescent [postnatal day (PND) 29-40] and adult (PND 50-61) male mice using the conditioned place preference paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1.25 or 10 mg/kg of MDMA. The effects of social defeat on corticosterone levels and the motor or the anxiogenic effects of MDMA were also evaluated. Mice exposed to social defeat during adulthood did not show conditioned place preference after conditioning with either dose of MDMA. Conversely, social defeat did not affect the anxiogenic and motor effects of MDMA. Adult mice exposed to social defeat showed higher levels of corticosterone than their controls and adolescent mice. Social stress did not induce behavioural effects in adolescent mice. Our results show that stress induced by social defeat decreases the sensitivity of adult mice to the rewarding effects of MDMA.

Maintenance of dominance status is necessary for resistance to social defeat stress in Syrian hamsters

PubMed Central

Morrison, Kathleen E.; Bader, Lauren R.; Clinard, Catherine T.; Gerhard, Danielle M.; Gross, Sonya E.; Cooper, Matthew A.

2014-01-01

Resilience is an active process that involves a discrete set of neural substrates and cellular mechanisms and enables individuals to avoid some of the negative consequences of extreme stress. We have previously shown that dominant individuals show less stress-induced changes in behavior compared to subordinates using a conditioned defeat model in male Syrian hamsters (Mesocricetus auratus). To rule out pre-existing differences between dominants and subordinates, we examined whether 14 days of dominance experience is required to reduce the conditioned defeat response and whether the development of conditioned defeat resistance correlates with defeat-induced neural activation in select brain regions. We paired hamsters in daily 5-min aggressive encounters for 1, 7, or 14 days and then exposed animals to 3, 5-min social defeat episodes. The next day animals received conditioned defeat testing which involved a 5-min social interaction test with a non-aggressive intruder. In separate animals brains were collected after social defeat for c-Fos immunohistochemistry. We found that 14-day dominants showed a decreased conditioned defeat response compared to 14-day subordinates and controls, while 1-day and 7-day dominants did not differ from their subordinate counterparts. Also, the duration of dominance relationship was associated with distinct patterns of defeat-induced neural activation such that only 14-day dominants showed elevated c-Fos immunoreactivity in the ventral medial prefrontal cortex, medial amygdala, and lateral portions of the ventral medial hypothalamus. Our data suggest that resistance to social stress develops during the maintenance of dominance relationships and is associated with experience-dependent neural plasticity in select brain regions. PMID:24875769

Guideposts for the U.S. Military in the Twenty-first Century

DTIC Science & Technology

2000-01-01

emphasizes cost over value , administration over output, and the separation of operators from engineers. To defeat complacency and regain superiority...teaching military values and culture. Increasingly, the lure of attractive, non-military careers poses a serious challenge to military retention. If we are...future conflicts-the vision that air power would be primarily of strategic value , carrying the war quickly and decisively to the heart of the enemy’s

Social defeat in adolescent mice increases vulnerability to alcohol consumption.

PubMed

Rodriguez-Arias, Marta; Navarrete, Francisco; Blanco-Gandia, Maria Carmen; Arenas, Maria Carmen; Bartoll-Andrés, Adrián; Aguilar, Maria A; Rubio, Gabriel; Miñarro, José; Manzanares, Jorge

2016-01-01

This study employs an oral operant conditioning paradigm to evaluate the effects of repeated social defeat during adolescence on the reinforcing and motivational actions of ethanol in adult OF1 mice. Social interaction, emotional and cognitive behavioral aspects were also analyzed, and real-time polymerase chain reaction (PCR) experiments were performed to study gene expression changes in the mesocorticolimbic and hypothalamus-hypophysis-adrenal (HHA) axis. Social defeat did not alter anxiety-like behavior in the elevated plus maze or cognitive performance in the passive avoidance and Hebb-Williams tests. A social interaction test revealed depression-like symptoms and social subordination behavior in defeated OF1 mice. Interestingly, social defeat in adolescence significantly increased the number of effective responses, ethanol consumption values and motivation to drink. Finally, real-time PCR analyses revealed that social defeat significantly increased tyrosine hydroxylase and corticotropin-releasing hormone in the ventral tegmental area and paraventricular nucleus, respectively. In contrast, mu-opioid receptor gene expression was decreased in the nucleus accumbens of socially defeated mice. In summary, these findings suggest that exposure to social defeat during adolescence increases vulnerability to the rewarding effects of ethanol without affecting emotional or cognitive performance. The gene expression alterations we have observed in the mesocorticolimbic and HHA axis systems of defeated mice could be related with their increased ethanol consumption. These results endorse future research into pharmacological strategies that modulate these systems for the treatment of social stress-related alcohol consumption problems. © 2014 Society for the Study of Addiction.

The prospective role of defeat and entrapment in depression and anxiety: a 12-month longitudinal study.

PubMed

Griffiths, Alys Wyn; Wood, Alex M; Maltby, John; Taylor, Peter J; Tai, Sara

2014-04-30

The concepts of "defeat" (representing failed social struggle) and "entrapment" (representing an inability to escape from a situation) have emerged from the animal literature, providing insight into the health consequences of low social rank. Evolutionary models suggest that these constructs co-occur and can lead to the development of mental disorders, although there is limited empirical evidence supporting these predictions. Participants (N=172) were recruited from economically deprived areas in North England. Over half of participants (58%) met clinical cut-offs for depression and anxiety, therefore we conducted analyses to establish whether participant outcomes were dependent on baseline defeat and entrapment levels. Participants completed measures of defeat, entrapment, depression and anxiety at two time-points twelve months apart. Factor analysis demonstrated that defeat and entrapment were best defined as one factor, suggesting that the experiences co-occurred. Regression analyses demonstrated that changes in depression and anxiety between T1 and T2 were predicted from baseline levels of defeat and entrapment; however, changes in defeat and entrapment were also predicted from baseline depression and anxiety. There are implications for targeting perceptions of defeat and entrapment within psychological interventions for people experiencing anxiety and depression and screening individuals to identify those at risk of developing psychopathology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cognitive and neural correlates of depression-like behaviour in socially defeated mice: an animal model of depression with cognitive dysfunction.

PubMed

Yu, Tao; Guo, Ming; Garza, Jacob; Rendon, Samantha; Sun, Xue-Li; Zhang, Wei; Lu, Xin-Yun

2011-04-01

Human depression is associated with cognitive deficits. It is critical to have valid animal models in order to investigate mechanisms and treatment strategies for these associated conditions. The goal of this study was to determine the association of cognitive dysfunction with depression-like behaviour in an animal model of depression and investigate the neural circuits underlying the behaviour. Mice that were exposed to social defeat for 14 d developed depression-like behaviour, i.e. anhedonia and social avoidance as indicated by reduced sucrose preference and decreased social interaction. The assessment of cognitive performance of defeated mice demonstrated impaired working memory in the T-maze continuous alternation task and enhanced fear memory in the contextual and cued fear-conditioning tests. In contrast, reference learning and memory in the Morris water maze test were intact in defeated mice. Neuronal activation following chronic social defeat was investigated by c-fosin-situ hybridization. Defeated mice exhibited preferential neural activity in the prefrontal cortex, cingulate cortex, hippocampal formation, septum, amygdala, and hypothalamic nuclei. Taken together, our results suggest that the chronic social defeat mouse model could serve as a valid animal model to study depression with cognitive impairments. The patterns of neuronal activation provide a neural basis for social defeat-induced changes in behaviour.

Episodic Social Stress-Escalated Cocaine Self-Administration: Role of Phasic and Tonic Corticotropin Releasing Factor in the Anterior and Posterior Ventral Tegmental Area.

PubMed

Holly, Elizabeth N; Boyson, Christopher O; Montagud-Romero, Sandra; Stein, Dirson J; Gobrogge, Kyle L; DeBold, Joseph F; Miczek, Klaus A

2016-04-06

Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats.In vivo microdialysis of CRF in the VTA demonstrated that CRF is phasically released in the posterior VTA (pVTA) during acute defeat, but, with repeated defeat, CRF is recruited into the anterior VTA (aVTA) and CRF tone is increased in both subregions. Intra-VTA antagonism of CRF-R1 in the pVTA and CRF-R2 in the aVTA during each social defeat prevented escalated cocaine self-administration in a 24 h "binge." VTA CRF continues to influence cocaine seeking in stressed animals long after social defeat exposure. Unlike nonstressed controls, previously stressed rats show significant cocaine seeking after 15 d of forced abstinence. Previously stressed rats continue to express elevated CRF tone within the VTA and antagonism of pVTA CRF-R1 or aVTA CRF-R2 reverses cocaine seeking. In conclusion, these experiments demonstrate neuroadaptive changes in tonic and phasic CRF with repeated stress, that CRF release during stress may contribute to later escalated cocaine taking, and that persistently elevated CRF tone in the VTA may drive later cocaine seeking through increased activation of pVTA CRF-R1 and aVTA CRF-R2. Corticotropin releasing factor (CRF) within the ventral tegmental area (VTA) has emerged as a likely candidate molecule underlying the fundamental link between stress history and escalated drug self-administration. However, the nature of CRF release in the VTA during acute and repeated stress, as well as its role in enduring neuroadaptations driving later drug taking and seeking, are poorly understood. These experiments explore how CRF is released and interacts with its receptors in specific regions of the VTA both during and after stress to fuel later escalated cocaine taking and seeking behavior. Understanding these acute and persistent changes to the VTA CRF system may lead to better therapeutic interventions for addiction. Copyright © 2016 the authors 0270-6474/16/364094-13$15.00/0.

Episodic Social Stress-Escalated Cocaine Self-Administration: Role of Phasic and Tonic Corticotropin Releasing Factor in the Anterior and Posterior Ventral Tegmental Area

PubMed Central

Boyson, Christopher O.; Montagud-Romero, Sandra; Stein, Dirson J.; Gobrogge, Kyle L.; DeBold, Joseph F.; Miczek, Klaus A.

2016-01-01

Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats. In vivo microdialysis of CRF in the VTA demonstrated that CRF is phasically released in the posterior VTA (pVTA) during acute defeat, but, with repeated defeat, CRF is recruited into the anterior VTA (aVTA) and CRF tone is increased in both subregions. Intra-VTA antagonism of CRF-R1 in the pVTA and CRF-R2 in the aVTA during each social defeat prevented escalated cocaine self-administration in a 24 h “binge.” VTA CRF continues to influence cocaine seeking in stressed animals long after social defeat exposure. Unlike nonstressed controls, previously stressed rats show significant cocaine seeking after 15 d of forced abstinence. Previously stressed rats continue to express elevated CRF tone within the VTA and antagonism of pVTA CRF-R1 or aVTA CRF-R2 reverses cocaine seeking. In conclusion, these experiments demonstrate neuroadaptive changes in tonic and phasic CRF with repeated stress, that CRF release during stress may contribute to later escalated cocaine taking, and that persistently elevated CRF tone in the VTA may drive later cocaine seeking through increased activation of pVTA CRF-R1 and aVTA CRF-R2. SIGNIFICANCE STATEMENT Corticotropin releasing factor (CRF) within the ventral tegmental area (VTA) has emerged as a likely candidate molecule underlying the fundamental link between stress history and escalated drug self-administration. However, the nature of CRF release in the VTA during acute and repeated stress, as well as its role in enduring neuroadaptations driving later drug taking and seeking, are poorly understood. These experiments explore how CRF is released and interacts with its receptors in specific regions of the VTA both during and after stress to fuel later escalated cocaine taking and seeking behavior. Understanding these acute and persistent changes to the VTA CRF system may lead to better therapeutic interventions for addiction. PMID:27053215

Trait reappraisal amplifies subjective defeat, sadness, and negative affect in response to failure versus success in nonclinical and psychosis populations.

PubMed

Johnson, Judith; Gooding, Patricia A; Wood, Alex M; Taylor, Peter J; Tarrier, Nicholas

2011-11-01

Perceptions of defeat have been linked to a range of clinical disorders including psychosis. Perceived defeat sometimes increases in response to failure, but the strength of this association varies between individuals. The present research investigated whether trait reappraisal, a thought-focused coping style, amplified response to stressful events. Two studies (Study 1, n = 120 nonclinical participants; Study 2, n = 77 participants with schizophrenia-spectrum disorders) investigated whether trait reappraisal amplified feelings of defeat following an experience of failure versus success. Frequent reappraisers showed the largest increases in subjective defeat after failure versus success in both studies, with nonclinical participants with greater habitual reappraisal also showing larger increases in sadness and general negative affect. Frequent use of reappraisal may confer vulnerability to subjective defeat in response to stressful life events among nonclinical and clinical populations and could be an area for relapse prevention interventions to target.

14 CFR 25.934 - Turbojet engine thrust reverser system tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Turbojet engine thrust reverser system... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.934 Turbojet engine thrust reverser system tests. Thrust reversers installed on turbojet engines must meet the...

Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior

PubMed Central

Riga, Danai; Theijs, J. Trisna; De Vries, Taco J.; Smit, August B.; Spijker, Sabine

2015-01-01

Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g., reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction, and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of five social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. PMID:26300748

Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior.

PubMed

Riga, Danai; Theijs, J Trisna; De Vries, Taco J; Smit, August B; Spijker, Sabine

2015-01-01

Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g., reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction, and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of five social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct.

Effects of striatal ΔFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice.

PubMed

Donahue, Rachel J; Muschamp, John W; Russo, Scott J; Nestler, Eric J; Carlezon, William A

2014-10-01

Chronic social defeat stress (CSDS) produces persistent behavioral adaptations in mice. In many behavioral assays, it can be difficult to determine if these adaptations reflect core signs of depression. We designed studies to characterize the effects of CSDS on sensitivity to reward because anhedonia (reduced sensitivity to reward) is a defining characteristic of depressive disorders in humans. We also examined the effects of striatal ΔFosB overexpression and the N-methyl-D-aspartate receptor antagonist ketamine, both of which promote resilience, on CSDS-induced alterations in reward function and social interaction. Intracranial self-stimulation (ICSS) was used to quantify CSDS-induced changes in reward function. Mice were implanted with lateral hypothalamic electrodes, and ICSS thresholds were measured after each of 10 daily CSDS sessions and during a 5-day recovery period. We also examined if acute intraperitoneal administration of ketamine (2.5-20 mg/kg) reverses CSDS-induced effects on reward or, in separate mice, social interaction. ICSS thresholds were increased by CSDS, indicating decreases in the rewarding impact of lateral hypothalamic stimulation (anhedonia). This effect was attenuated in mice overexpressing ∆FosB in striatum, consistent with pro-resilient actions of this transcription factor. High, but not low, doses of ketamine administered after completion of the CSDS regimen attenuated social avoidance in defeated mice, although this effect was transient. Ketamine did not block CSDS-induced anhedonia in the ICSS test. This study found that CSDS triggers persistent anhedonia and confirms that ΔFosB overexpression produces stress resilience. The findings of this study also indicate that acute administration of ketamine fails to attenuate CSDS-induced anhedonia despite reducing other depression-related behavioral abnormalities. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?

PubMed

Nagata, Shinobu; Seki, Yoichi; Shibuya, Takayuki; Yokoo, Mizue; Murata, Tomokazu; Hiramatsu, Yoichi; Yamada, Fuminori; Ibuki, Hanae; Minamitani, Noriko; Yoshinaga, Naoki; Kusunoki, Muga; Inada, Yasushi; Kawasoe, Nobuko; Adachi, Soichiro; Oshiro, Keiko; Matsuzawa, Daisuke; Hirano, Yoshiyuki; Yoshimura, Kensuke; Nakazato, Michiko; Iyo, Masaomi; Nakagawa, Akiko; Shimizu, Eiji

2018-01-12

Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group. Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).

Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice.

PubMed

Wohleb, Eric S; Fenn, Ashley M; Pacenta, Ann M; Powell, Nicole D; Sheridan, John F; Godbout, Jonathan P

2012-09-01

Repeated social defeat (RSD) activates neuroendocrine pathways that have a significant influence on immunity and behavior. Previous studies from our lab indicate that RSD enhances the inflammatory capacity of CD11b⁺ cells in the brain and promotes anxiety-like behavior in an interleukin (IL)-1 and β-adrenergic receptor-dependent manner. The purpose of this study was to determine the degree to which mice subjected to RSD were more responsive to a secondary immune challenge. Therefore, RSD or control (HCC) mice were injected with saline or lipopolysaccharide (LPS) and activation of brain CD11b⁺ cells and behavioral responses were determined. Peripheral LPS (0.5 mg/kg) injection caused an extended sickness response with exaggerated weight loss and prolonged social withdrawal in socially defeated mice. LPS injection also amplified mRNA expression of IL-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD14 in enriched CD11b⁺ cells isolated from socially defeated mice. In addition, IL-1β mRNA levels in enriched CD11b⁺ cells remained elevated in socially defeated mice 24 h and 72 h after LPS. Moreover, microglia and CNS macrophages isolated from socially defeated mice had the highest CD14 expression after LPS injection. Both social defeat and LPS injection increased the percentage of CD11b⁺/CD45(high) macrophages in the brain and the number of inflammatory macrophages (CD11b⁺/CD45(high)/CCR2⁺) was highest in RSD-LPS mice. Anxiety-like behavior was increased by social defeat, but was not exacerbated by the LPS challenge. Nonetheless, reduced locomotor activity and increased social withdrawal were still present in socially defeated mice 72 h after LPS. Last, LPS-induced microglia activation was most evident in the hippocampus of socially defeated mice. Taken together, these findings demonstrate that repeated social defeat enhanced the neuroinflammatory response and caused prolonged sickness following innate immune challenge. Published by Elsevier Ltd.

Research Contributing to Psychological Health and Traumatic Brain Injury Programs and Guidance

DTIC Science & Technology

2011-01-24

AGP, 2004)  Panic disorder (e.g., Roy-Byrne et al, AGP 2005)  Somatic symptoms (e.g., Smith et al, AGP 1995)  Health anxiety (e.g., Barsky et al...management of concussed service members and those with recurrent concussion  Transition from symptom driven reporting to incident driven DESIRED END STATE...and Readiness DDR&E = Director, Defense Research & Engineering JIEDDO = Joint Improvised Explosive Device Defeat Organization BIR PCO = Blast Injury

The Secret of Future Defeat: The Evolution of US Joint and Army Doctrine 1993-2006 and the Flawed Conception of Stability Operations

DTIC Science & Technology

2007-05-24

The Secret of Future Defeat: the Evolution of US Joint and Army Doctrine 1993-2006 and the Flawed Conception of Stability Operations A...4. TITLE AND SUBTITLE The Secret of Future Defeat: the Evolution of US Joint and 5a. CONTRACT NUMBER Army Doctrine 1993-2006 and the Flawed... The Secret of Future Defeat: the Evolution of US Joint and Army Doctrine 1993-2006 and the Flawed Conception of Stability Operations Approved by

β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat.

PubMed

Wohleb, Eric S; Hanke, Mark L; Corona, Angela W; Powell, Nicole D; Stiner, La'Tonia M; Bailey, Michael T; Nelson, Randy J; Godbout, Jonathan P; Sheridan, John F

2011-04-27

Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.

β-Adrenergic Receptor Antagonism Prevents Anxiety-like Behavior and Microglial Reactivity Induced by Repeated Social Defeat

PubMed Central

Wohleb, Eric S.; Hanke, Mark L.; Corona, Angela W.; Powell, Nicole D.; Stiner, La'Tonia M.; Bailey, Michael T.; Nelson, Randy J.; Godbout, Jonathan P.; Sheridan, John F.

2011-01-01

Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of de-ramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes (GILZ and FKBP51). The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1) after stimulation with lipopolysaccharide (LPS) compared to microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1 deficient (IL-1r1-/-) mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors. PMID:21525267

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

PubMed

Duque, Aránzazu; Vinader-Caerols, Concepción; Monleón, Santiago

2017-01-01

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

PubMed Central

Duque, Aránzazu; Vinader-Caerols, Concepción

2017-01-01

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10–12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity. PMID:28278165

A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality.

PubMed

Siddaway, Andy P; Taylor, Peter J; Wood, Alex M; Schulz, Joerg

2015-09-15

There is a burgeoning literature examining perceptions of being defeated or trapped in different psychiatric disorders. The disorders most frequently examined to date are depression, anxiety problems, posttraumatic stress disorder (PTSD), and suicidality. To quantify the size and consistency of perceptions of defeat and entrapment in depression, anxiety problems, PTSD and suicidality, test for differences across psychiatric disorders, and examine potential moderators and publication bias. Random-effects meta-analyses based on Pearson's correlation coefficient r. Forty studies were included in the meta-analysis (n = 10,072). Perceptions of defeat and entrapment were strong (around r = 0.60) and similar in size across all four psychiatric disorders. Perceptions of defeat were particularly strong in depression (r = 0.73). There was no between-study heterogeneity; therefore moderator analyses were conducted in an exploratory fashion. There was no evidence of publication bias. Analyses were cross-sectional, which precludes establishing temporal precedence or causality. Some of the meta-analyses were based on relatively small numbers of effect sizes, which may limit their generalisability. Perceptions of defeat and entrapment are clinically important in depression, anxiety problems, PTSD, and suicidality. Similar-sized, strong relationships across four different psychiatric disorders could suggest that perceptions of defeat and entrapment are transdiagnostic constructs. The results suggest that clinicians and researchers need to become more aware of perceptions of defeat and entrapment. Copyright © 2015 Elsevier B.V. All rights reserved.

Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior.

PubMed

Kabbaj, M; Norton, C S; Kollack-Walker, S; Watson, S J; Robinson, T E; Akil, H

2001-12-01

It is known that social defeat can modulate cocaine self-administration. However, it is unclear whether this psychosocial stressor affects drug-taking behavior to the same extent across all individual animals, particularly those with differing propensities to self-administer psychostimulants. This study examined the effect of social defeat on cocaine self-administration in animals that differ in novelty-seeking behavior that predicts differences in drug self-administration. Male Sprague-Dawley rats were first classified into high-responder (HR) and low-responder (LR) groups. HR and LR rats were categorized based on their locomotor activity in a novel environment, with HR rats exhibiting higher locomotor activity than LR rats. Then, male rats were exposed on four occasions to an aggressive Long Evans male rat over the course of 4 days. Control rats were not exposed to the social defeat. All rats were subsequently implanted with jugular catheters and 3 days later placed into the self-administration box to study the acquisition of cocaine self-administration (0.25 mg per infusion). HR non-defeated animals self-administered more cocaine than the LR non-defeated animals. Following social defeat, the acquisition of cocaine self-administration is significantly delayed in HR rats and enhanced in LR rats. CONCLUSION The unique patterns of responsiveness in the HR and LR animals suggest that social defeat plays a role of equalizer of individual differences in drug-taking behavior.

Defeating a Cause: Anatomy of Defeat for Conflicts Involving Non-Nation-States

DTIC Science & Technology

2006-06-16

Sigmund Freud , "Why War?" 19 The psychological and sociological impacts of defeat have two major trends. Firstly, the works predominantly focus...Department of Government, Harvard University. Freud , Sigmund . 1964. Why war? In War: Studies from psychology, sociology, anthropology. Edited by

Persistent escalation of alcohol consumption by mice exposed to brief episodes of social defeat stress: suppression by CRF-R1 antagonism.

PubMed

Newman, Emily L; Albrechet-Souza, Lucas; Andrew, Peter M; Auld, John G; Burk, Kelly C; Hwa, Lara S; Zhang, Eric Y; DeBold, Joseph F; Miczek, Klaus A

2018-06-01

Episodic bouts of social stress can precede the initiation, escalation, or relapse to disordered alcohol intake. Social stress may engender neuroadaptations in the hypothalamic-pituitary-adrenal (HPA) axis and in extrahypothalamic stress circuitry to promote the escalation of alcohol intake. We aimed to (1) confirm a pattern of escalated drinking in socially defeated mice and to (2) test drugs that target distinct aspects of the HPA axis and extrahypothalamic neural substrates for their effectiveness in reducing murine, stress-escalated drinking. Male C57BL/6J (B6) mice were socially defeated by resident Swiss-derived males for ten consecutive days receiving 30 bites/day. Ten days after the final defeat, cohorts of B6 mice received continuous or intermittent access to 20% EtOH (w/v) and water. After 4 weeks of drinking, mice were injected with weekly, systemic doses of the CRF-R1 antagonist, CP376395; the glucocorticoid receptor antagonist, mifepristone; the 11-beta-hydroxylase inhibitor, metyrapone; or the 5-alpha-reductase inhibitor, finasteride. Prior to drug treatments, defeated mice reliably consumed more EtOH than non-defeated controls, and mice given alcohol intermittently consumed more EtOH than those with continuous access. CP376395 (17-30 mg/kg) reduced continuous, but not intermittent EtOH intake (g/kg) in socially defeated mice. Mifepristone (100 mg/kg), however, increased drinking by defeated mice with intermittent access to alcohol while reducing drinking during continuous access. When administered finasteride (100 mg/kg) or metyrapone (50 mg/kg), all mice reduced their EtOH intake while increasing their water consumption. Mice with a history of episodic social defeat stress were selectively sensitive to the effects of CRF-R1 antagonism, suggesting that CRF-R1 may be a potential target for treating alcohol use disorders in individuals who escalate their drinking after exposure to repeated bouts of psychosocial stress. Future studies will clarify how social defeat stress may alter the expression of extrahypothalamic CRF-R1 and glucocorticoid receptors.

Sex Differences in Social Interaction Behavior Following Social Defeat Stress in the Monogamous California Mouse (Peromyscus californicus)

PubMed Central

Trainor, Brian C.; Pride, Michael C.; Villalon Landeros, Rosalina; Knoblauch, Nicholas W.; Takahashi, Elizabeth Y.; Silva, Andrea L.; Crean, Katie K.

2011-01-01

Stressful life experiences are known to be a precipitating factor for many mental disorders. The social defeat model induces behavioral responses in rodents (e.g. reduced social interaction) that are similar to behavioral patterns associated with mood disorders. The model has contributed to the discovery of novel mechanisms regulating behavioral responses to stress, but its utility has been largely limited to males. This is disadvantageous because most mood disorders have a higher incidence in women versus men. Male and female California mice (Peromyscus californicus) aggressively defend territories, which allowed us to observe the effects of social defeat in both sexes. In two experiments, mice were exposed to three social defeat or control episodes. Mice were then behaviorally phenotyped, and indirect markers of brain activity and corticosterone responses to a novel social stimulus were assessed. Sex differences in behavioral responses to social stress were long lasting (4 wks). Social defeat reduced social interaction responses in females but not males. In females, social defeat induced an increase in the number of phosphorylated CREB positive cells in the nucleus accumbens shell after exposure to a novel social stimulus. This effect of defeat was not observed in males. The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test. These data suggest that California mice could be a useful model for studying sex differences in behavioral responses to stress, particularly in neurobiological mechanisms that are involved with the regulation of social behavior. PMID:21364768

Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio

PubMed Central

Henriques-Alves, Aron M.; Queiroz, Claudio M.

2016-01-01

In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress. PMID:26869895

The effects of social defeat on behavior and dopaminergic markers in mice.

PubMed

Jin, H-M; Shrestha Muna, S; Bagalkot, T R; Cui, Y; Yadav, B K; Chung, Y-C

2015-03-12

The present study investigated the effects of chronic social defeat stress on several behavioral parameters, and the expression of dopaminergic markers, i.e., dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse brains. After 10days of social defeat stress, the defeated mice were divided into two groups: one group underwent a series of behavioral tests. The other group was sacrificed on the 11th day and tissue samples were collected for Western blotting. The behavioral tests comprised tests of locomotion, light/dark preference, social interaction, as well as the novel object recognition test (NORT), Morris water maze, and forced swimming test (FST). We measured the expression of D1Rs, D2Rs, total DARPP-32, phospho-Thr34 or Thr75-DARPP-32 using Western blotting. The defeated mice showed increased anxiety- and depression-like behaviors, and impaired cognition. No significant differences in D1Rs and D2Rs expression were shown between defeated and control mice in any area studied. A significantly increased expression in total DARPP-32, and phospho-DARPP-32 was observed in the PFC or AMY of defeated mice. These data suggest that alterations in dopaminergic markers may be involved in anxiety- and depression-like behaviors, and cognitive impairment induced by social defeat stress. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio.

PubMed

Henriques-Alves, Aron M; Queiroz, Claudio M

2015-01-01

In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress.

Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice.

PubMed

Zhao, Tong; Huang, Guang-Biao; Muna, Sushma Shrestha; Bagalkot, Tarique Rajasaheb; Jin, Hong-Mei; Chae, Han-Jung; Chung, Young-Chul

2013-07-01

Social defeat stress induces physiological and behavioral symptoms, including anxiety, anhedonia, immune deficits, and altered expression of key brain genes. The present study investigated the effects of social defeat stress on the behaviors and expressions of Chat, Grp78, and chop in the brains of adult mice. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. In experiment 1, behavioral tests were conducted, and brains were processed for Western blotting at day 27 after stress. In experiment 2, social avoidance tests were conducted, and brains were processed for Western blotting at day 12 after stress. The results indicate decreased and increased locomotion and anxiety behavior in all defeated mice. Decrease in social interaction, increased immobility, and impaired memory performance were only observed in susceptible mice. A decrease in the Chat level at days 12 and 27 was noted in the prefrontal cortex (PFC), amygdala (Amyg), and dorsal hippocampus (HIP) in defeated mice. The expression levels of Grp78 and chop measured on days 12 and 27 were significantly greater in the Amyg of susceptible mice. In the PFC and HIP, defeated mice displayed different patterns in the levels of Grp78 and chop expressions measured on days 12 and 27. The present study demonstrated that chronic social defeat stress in mice produces stress-related behaviors. Different response patterns were noted for Grp78 and chop expression among the groups in terms of brain regions and time-course effects.

Germany in Defeat, 1918 and 1945: Some Comparisons and Contrasts.

ERIC Educational Resources Information Center

Diehl, James M.

1989-01-01

Analyzes how Germans viewed defeat after the two world wars, and how these perceptions influenced subsequent political developments. Compares questions of guilt and responsibility following the two wars. Examines the growth of democracy, its defeat after World War I, and success after World War II. Discusses the influences of the occupation…

The Role of Defeat and Entrapment in Depression, Anxiety, and Suicide

ERIC Educational Resources Information Center

Taylor, Peter James; Gooding, Patricia; Wood, Alex M.; Tarrier, Nicholas

2011-01-01

Defeat and entrapment are psychological constructs that have played a central role in evolutionary accounts of depression. These concepts have since been implicated in theoretical accounts of anxiety disorders and suicidality. The current article reports on a systematic review of the existing research investigating the links among defeat,…

Chronic social defeat induces long-term behavioral depression of aggressive motivation in an invertebrate model system.

PubMed

Rose, Jacqueline; Rillich, Jan; Stevenson, Paul A

2017-01-01

Losing a fight against a conspecific male (social defeat) induces a period of suppressed aggressiveness and general behaviour, often with symptoms common to human psychiatric disorders. Agonistic experience is also discussed as a potential cause of consistent, behavioral differences between individuals (animal "personality"). In non-mammals, however, the impact of single agonistic encounters typically last only hours, but then again studies of repeated intermittent defeat (chronic social defeat) are seldom. We report the effect of chronic social defeat in adult male crickets (Gryllus bimaculatus), for which all known behavioral effects of defeat last only 3 h. Firstly, after 48 h social isolation, crickets that experienced 5 defeats at 24 h intervals against the same, weight-matched opponent exhibited suppressed aggressiveness lasting >24 h, which was still evident when the animals were matched against an unfamiliar opponent at the last trial. Secondly, this longer-term depression of aggression also occurred in 48 h isolated crickets that lost 6 fights at 1 h intervals against unfamiliar opponents at each trial. Thirdly, crickets isolated as larvae until adult maturity (>16 days) were significantly more aggressive, and less variable in their aggressiveness at their very first fight than 48 h isolates, and also significantly more resilient to the effects of chronic social defeat. We conclude that losing an aggressive encounter in crickets has a residual effect, lasting at least 24 h, that accumulates when repeated defeats are experienced, and leads to a prolonged depression of aggressive motivation in subordinates. Furthermore, our data indicate that social interactions between young adults and possibly larvae can have even longer, possibly lifelong influences on subsequent behavior. Social subjugation is thus likely to be a prime determinant of inter-individual behavioral differences in crickets. Our work also opens new avenues for investigating proximate mechanisms underlying depression-like phenomena.

Icaritin opposes the development of social aversion after defeat stress via increases of GR mRNA and BDNF mRNA in mice.

PubMed

Wu, Xiao; Wu, Jinfeng; Xia, Shijin; Li, Bei; Dong, Jingcheng

2013-11-01

Icariin is a major constituent of flavonoids isolated from Herba Epimedii. Several previous studies have demonstrated the antidepressant-like effects of icariin. After oral administration of icariin, 19 metabolites of icariin were detected in rat plasma. Icaritin is one such of metabolite of icariin. In this study, a chronic social defeat protocol is used as a mouse model for depression, and the effects of icaritin administration on social avoidance are investigated. The data indicates that icaritin (5mg/kg and 10mg/kg) oral administration opposes the development of social aversion after defeat stress. In vitro corticosterone sensitivity assay demonstrated that icaritin partially restored social defeat-induced impairment of glucocorticoid sensitivity. The expressions of GR mRNA and BDNFmRNA in the hippocampus were increased after icaritin treatment. Meanwhile, the social defeat-induced increases in CRH mRNA in hypothalamus were restored by icaritin administration. Our data also suggests that icaritin administration remarkably attenuated the increases in serum IL-6 and TNF-α level that occur following exposure to social defeat. In conclusion, icaritin is a novel antidepressant. It partially restored social defeat-induced impairment of glucocorticoid sensitivity, HPA axis hyperactivity. These effects are at least partially attributed to normalization of the GR function and increases in BDNF expression. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of Competitive Outcomes and Margins of Victory/Defeat on Practice Behavior and Performance Quality.

ERIC Educational Resources Information Center

Grove, J. Robert; And Others

To determine the influence of successful or unsuccessful competitive outcomes and small or large margins of victory/defeat on performance, pairs of female undergraduate students "competed" against each other in a dart tossing contest. False feedback about the outcomes and margin of victory/defeat led subjects to believe they were winning every…

Is the Medial Amygdala Part of the Neural Circuit Modulating Conditioned Defeat in Syrian Hamsters?

ERIC Educational Resources Information Center

Markham, Chris M.; Huhman, Kim L.

2008-01-01

Conditioned defeat is a model wherein hamsters that have previously experienced a single social defeat subsequently exhibit heightened levels of avoidance and submission in response to a smaller, non-aggressive intruder. While we have previously demonstrated the critical involvement of the basolateral and central nuclei of the amygdala in the…

Repeated social stress leads to contrasting patterns of structural plasticity in the amygdala and hippocampus.

PubMed

Patel, D; Anilkumar, S; Chattarji, S; Buwalda, B

2018-03-23

Previous studies have demonstrated that repeated immobilization and restraint stress cause contrasting patterns of dendritic reorganization as well as alterations in spine density in amygdalar and hippocampal neurons. Whether social and ethologically relevant stressors can induce similar patterns of morphological plasticity remains largely unexplored. Hence, we assessed the effects of repeated social defeat stress on neuronal morphology in basolateral amygdala (BLA), hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats experienced social defeat stress on 5 consecutive days during confrontation in the resident-intruder paradigm with larger and aggressive Wild-type Groningen rats. This resulted in clear social avoidance behavior one day after the last confrontation. To assess the morphological consequences of repeated social defeat, 2 weeks after the last defeat, animals were sacrificed and brains were stained using a Golgi-Cox procedure. Morphometric analyses revealed that, compared to controls, defeated Wistar rats showed apical dendritic decrease in spine density on CA1 but not BLA. Sholl analysis demonstrated a significant dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in defeated animals. Social stress failed to induce lasting structural changes in mPFC neurons. Our findings demonstrate for the first time that social defeat stress elicits divergent patterns of structural plasticity in the hippocampus versus amygdala, similar to what has previously been reported with repeated physical stressors. Therefore, brain region specific variations may be a universal feature of stress-induced plasticity that is shared by both physical and social stressors. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex differences in effects of dopamine D1 receptors on social withdrawal.

PubMed

Campi, Katharine L; Greenberg, Gian D; Kapoor, Amita; Ziegler, Toni E; Trainor, Brian C

2014-02-01

Dopamine signaling in the nucleus accumbens (NAc) plays a critical role in the regulation of motivational states. Recent studies in male rodents show that social defeat stress increases the activity of ventral tegmental dopamine neurons projecting to the NAc, and that this increased activity is necessary for stress-induced social withdrawal. Domestic female mice are not similarly aggressive, which has hindered complementary studies in females. Using the monogamous California mouse (Peromyscus californicus), we found that social defeat increased total dopamine, DOPAC, and HVA content in the NAc in both males and females. These results are generally consistent with previous studies in Mus, and suggest defeat stress also increases NAc dopamine signaling in females. However, these results do not explain our previous observations that defeat stress induces social withdrawal in female but not male California mice. Pharmacological manipulations provided more insights. When 500 ng of the D1 agonist SKF38393 was infused in the NAc shell of females that were naïve to defeat, social interaction behavior was reduced. This same dose of SKF38393 had no effect in males, suggesting that D1 receptor activation is sufficient to induce social withdrawal in females but not males. Intra-accumbens infusion of the D1 antagonist SCH23390 increased social approach behavior in females exposed to defeat but not in females naïve to defeat. This result suggests that D1 receptors are necessary for defeat-induced social withdrawal. Overall, our results suggest that sex differences in molecular pathways that are regulated by D1 receptors contribute to sex differences in social withdrawal behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

14 CFR 23.934 - Turbojet and turbofan engine thrust reverser systems tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Turbojet and turbofan engine thrust... CATEGORY AIRPLANES Powerplant General § 23.934 Turbojet and turbofan engine thrust reverser systems tests. Thrust reverser systems of turbojet or turbofan engines must meet the requirements of § 33.97 of this...

14 CFR 23.1155 - Turbine engine reverse thrust and propeller pitch settings below the flight regime.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Turbine engine reverse thrust and propeller... COMMUTER CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 23.1155 Turbine engine reverse thrust and propeller pitch settings below the flight regime. For turbine engine installations, each...

14 CFR 23.1155 - Turbine engine reverse thrust and propeller pitch settings below the flight regime.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Turbine engine reverse thrust and propeller... COMMUTER CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 23.1155 Turbine engine reverse thrust and propeller pitch settings below the flight regime. For turbine engine installations, each...

14 CFR 23.1155 - Turbine engine reverse thrust and propeller pitch settings below the flight regime.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Turbine engine reverse thrust and propeller... COMMUTER CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 23.1155 Turbine engine reverse thrust and propeller pitch settings below the flight regime. For turbine engine installations, each...

14 CFR 23.1155 - Turbine engine reverse thrust and propeller pitch settings below the flight regime.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Turbine engine reverse thrust and propeller... COMMUTER CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 23.1155 Turbine engine reverse thrust and propeller pitch settings below the flight regime. For turbine engine installations, each...

14 CFR 23.1155 - Turbine engine reverse thrust and propeller pitch settings below the flight regime.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Turbine engine reverse thrust and propeller... COMMUTER CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 23.1155 Turbine engine reverse thrust and propeller pitch settings below the flight regime. For turbine engine installations, each...

Restraint stress and social defeat: What they have in common.

PubMed

Motta, Simone Cristina; Canteras, Newton Sabino

2015-07-01

Bob Blanchard was a great inspiration for our studies on the neural basis of social defense. In the present study, we compared the hypothalamic pattern of activation between social defeat and restraint stress. As important stress situations, both defeated and immobilized animals displayed a substantial increase in Fos in the parvicellular part of the paraventricular nucleus,mostly in the region that contains the CRH neurons. In addition, socially defeated animals, but not restrained animals, recruited elements of the medial hypothalamic conspecific-responsive circuit, a region also engaged in other forms of social behavior. Of particular interest, both defeated and immobilized animals presented a robust increase in Fos expression in specific regions of the lateral hypothalamic area (i.e., juxtaparaventricular and juxtadorsomedial regions) likely to convey septo-hippocampal information encoding the environmental boundary restriction observed in both forms of stress, and in the dorsomedial part of the dorsal premammillary nucleus which seems to work as a key player for the expression of, at least, part of the behavioral responses during both restraint and social defeat. These results indicate interesting commonalities between social defeat and restraint stress, suggesting, for the first time, a septo-hippocampal–hypothalamic path likely to respond to the environmental boundary restriction that may act as common stressor component for both types of stress. Moreover, the comparison of the neural circuits mediating physical restraint and social defense revealed a possible path for encoding the entrapment component during social confrontation.

Extending the boundaries of reverse engineering

NASA Astrophysics Data System (ADS)

Lawrie, Chris

2002-04-01

In today's market place the potential of Reverse Engineering as a time compression tool is commonly lost under its traditional definition. The term Reverse Engineering was coined way back at the advent of CMM machines and 3D CAD systems to describe the process of fitting surfaces to captured point data. Since these early beginnings, downstream hardware scanning and digitising systems have evolved in parallel with an upstream demand, greatly increasing the potential of a point cloud data set within engineering design and manufacturing processes. The paper will discuss the issues surrounding Reverse Engineering at the turn of the millennium.

Proteolytic Cleavage of ProBDNF into Mature BDNF in the Basolateral Amygdala Is Necessary for Defeat-Induced Social Avoidance

ERIC Educational Resources Information Center

Dulka, Brooke N.; Ford, Ellen C.; Lee, Melissa A.; Donnell, Nathaniel J.; Goode, Travis D.; Prosser, Rebecca; Cooper, Matthew A.

2016-01-01

Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in…

Dominance relationships in Syrian hamsters modulate neuroendocrine and behavioral responses to social stress.

PubMed

Dulka, Brooke N; Koul-Tiwari, Richa; Grizzell, J Alex; Harvey, Marquinta L; Datta, Subimal; Cooper, Matthew A

2018-06-22

Stress is a well-known risk factor for psychopathology and rodent models of social defeat have strong face, etiological, construct and predictive validity for these conditions. Syrian hamsters are highly aggressive and territorial, but after an acute social defeat experience they become submissive and no longer defend their home territory, even from a smaller, non-aggressive intruder. This defeat-induced change in social behavior is called conditioned defeat (CD). We have shown that dominant hamsters show increased neural activity in the ventromedial prefrontal cortex (vmPFC) following social defeat stress and exhibit a reduced CD response at social interaction testing compared to subordinates. Although the vmPFC can inhibit the neuroendocrine stress response, it is unknown whether dominants and subordinates differ in stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that, following acute social defeat, dominants exhibit decreased submissive and defensive behavior compared to subordinates but do not differ from subordinates or social status controls (SSCs) in defeat-induced cortisol concentrations. Furthermore, both dominants and SSCs show greater corticotropin-releasing hormone (CRH) mRNA expression in the basolateral/central amygdala compared to subordinates, while there was no effect of social status on CRH mRNA expression in the paraventricular nucleus of the hypothalamus or bed nucleus of the stria terminalis. Overall, status-dependent differences in the CD response do not appear linked to changes in stress-induced cortisol concentrations or CRH gene expression, which is consistent with the view that stress resilience is not a lack of a physiological stress response but the addition of stress coping mechanisms. Lay summary Dominant hamsters show resistance to the behavioral effects of acute social defeat compared to subordinates, but it is unclear whether social status modulates the neuroendocrine stress response in Syrian hamsters. This study indicates that dominant social status does not alter stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis, which suggests that the ability of dominants to cope with social defeat stress is not associated with changes in their neuroendocrine stress response.

Large-Scale Wind-Tunnel Tests of Exhaust Ingestion Due to Thrust Reversal on a Four-Engine Jet Transport during Ground Roll

NASA Technical Reports Server (NTRS)

Tolhurst, William H., Jr.; Hickey, David H.; Aoyagi, Kiyoshi

1961-01-01

Wind-tunnel tests have been conducted on a large-scale model of a swept-wing jet transport type airplane to study the factors affecting exhaust gas ingestion into the engine inlets when thrust reversal is used during ground roll. The model was equipped with four small jet engines mounted in nacelles beneath the wing. The tests included studies of both cascade and target type reversers. The data obtained included the free-stream velocity at the occurrence of exhaust gas ingestion in the outboard engine and the increment of drag due to thrust reversal for various modifications of thrust reverser configuration. Motion picture films of smoke flow studies were also obtained to supplement the data. The results show that the free-stream velocity at which ingestion occurred in the outboard engines could be reduced considerably, by simple modifications to the reversers, without reducing the effective drag due to reversed thrust.

Cardiovascular disease 2005--the global picture.

PubMed

Callow, Allan D

2006-11-01

Although the past twenty years have seen a remarkable decline in the death rates of heart disease and stroke in the United States and several countries of western Europe, a reverse trend is occurring in other parts of the world. This is especially true in sub-Saharan Africa, India, China and Russia. World-wide, deaths from cardiovascular disease exceed those caused by cancer, infectious disease and trauma, constituting a deadly epidemic. Yet, in 1996 the Victoria Declaration stated that the world has the knowledge to eliminate cardiovascular disease as a major illness. Defeating such an initiative are other priorities such as education, housing, transportation, defense, as well as ignorance. The Earth Institute has labeled the needed effort, "A Race Against Time".

Reverse thrust performance of the QCSEE variable pitch turbofan engine

NASA Technical Reports Server (NTRS)

Samanich, N. E.; Reemsnyder, D. C.; Blodmer, H. E.

1980-01-01

Results of steady state reverse and forward to reverse thrust transient performance tests are presented. The original quiet, clean, short haul, experimental engine four segment variable fan nozzle was retested in reverse and compared with a continuous, 30 deg half angle conical exlet. Data indicated that the significantly more stable, higher pressure recovery flow with the fixed 30 deg exlet resulted in lower engine vibrations, lower fan blade stress, and approximately a 20 percent improvement in reverse thrust. Objective reverse thrust of 35 percent of takeoff thrust was reached. Thrust response of less than 1.5 sec was achieved for the approach and the takeoff to reverse thrust transients.

Impact of tobacco industry and other corporations in the defeat of the 1994 Clinton health care plan.

PubMed

Givel, Michael

2017-06-21

The primary reason cited by many scholars for the defeat of the Clinton Administration's 1994 health care reform bill has long been identified as Health Insurance Association of America and National Federation of Independent Businesses opposition to the bill. Given this predominant consensus combined with sizeable proposed funding for the bill by a large tobacco product tax, this manuscript examined what the tobacco industry's role was in whole or part in defeating the Clinton health care bill. This research occurred through crosschecking internal tobacco industry documents and Clinton White House documents. Prior to the passage of the bill, the tobacco industry accepted a compromise of 45 cents per pack increase phased in over five years. Due to this compromise, the industry or third party allies had no role in the ultimate defeat in the bill. The primary reason for the bill's ultimate defeat was general business (but not tobacco industry and third party ally) opposition, the bill running out of time, and conflicting bills. Secondary reasons for the bill's defeat included issues with: employer mandates, high taxes on insurance plans, impacts on medical research and education, Congressional attention to other issues, election year politics, and possible future excise tax possibilities.

Effect of social defeat in a territorial bird (Parus major) selected for different coping styles.

PubMed

Carere, C; Welink, D; Drent, P J; Koolhaas, J M; Groothuis, T G

2001-06-01

We addressed the questions (i) whether a social defeat triggers similar autonomic and behavioral responses in birds as is known from mammals and (ii) whether individuals that differ in coping style differ in their reaction to a social defeat. Adult captive male great tits (Parus major) from either of two different selection lines for coping style were used to test the effect of social defeat by an aggressive resident male conspecific on subsequent social and nonsocial behaviour, body temperature, breath rate and body mass. These parameters were measured 1 day before (baseline), immediately after and at Days 1 to 3 and 6 after the social interaction took place (Day 0). Social defeat decreased social exploration and increased body temperature substantially for at least 1 day in all birds. Breath rate and body mass were not affected. Birds belonging to the more aggressive and bolder line showed impairment in activity immediately after the social defeat. This is to our knowledge the first report showing that psychosocial stress in birds can have a similar impact as in rodents, but with a shorter recovery time. This might be due to species-specific differences in sensitivity to social stress, or to differences in the way social stress was induced.

Defeat and entrapment: more than meets the eye? Applying network analysis to estimate dimensions of highly correlated constructs.

PubMed

Forkmann, Thomas; Teismann, Tobias; Stenzel, Jana-Sophie; Glaesmer, Heide; de Beurs, Derek

2018-01-25

Defeat and entrapment have been shown to be of central relevance to the development of different disorders. However, it remains unclear whether they represent two distinct constructs or one overall latent variable. One reason for the unclarity is that traditional factor analytic techniques have trouble estimating the right number of clusters in highly correlated data. In this study, we applied a novel approach based on network analysis that can deal with correlated data to establish whether defeat and entrapment are best thought of as one or multiple constructs. Explanatory graph analysis was used to estimate the number of dimensions within the 32 items that make up the defeat and entrapment scales in two samples: an online community sample of 480 participants, and a clinical sample of 147 inpatients admitted to a psychiatric hospital after a suicidal attempt or severe suicidal crisis. Confirmatory Factor analysis (CFA) was used to test whether the proposed structure fits the data. In both samples, bootstrapped exploratory graph analysis suggested that the defeat and entrapment items belonged to different dimensions. Within the entrapment items, two separate dimensions were detected, labelled internal and external entrapment. Defeat appeared to be multifaceted only in the online sample. When comparing the CFA outcomes of the one, two, three and four factor models, the one factor model was preferred. Defeat and entrapment can be viewed as distinct, yet, highly associated constructs. Thus, although replication is needed, results are in line with theories differentiating between these two constructs.

14 CFR 23.933 - Reversing systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... analysis and testing completed by the engine and propeller manufacturers. [Doc. No. 26344, 58 FR 18971, Apr... only must be designed so that, during any reversal in flight, the engine will produce no more than... engine from producing more than idle thrust when the reversing system malfunctions; except that it may...

14 CFR 23.933 - Reversing systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... analysis and testing completed by the engine and propeller manufacturers. [Doc. No. 26344, 58 FR 18971, Apr... only must be designed so that, during any reversal in flight, the engine will produce no more than... engine from producing more than idle thrust when the reversing system malfunctions; except that it may...

14 CFR 23.933 - Reversing systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... analysis and testing completed by the engine and propeller manufacturers. [Doc. No. 26344, 58 FR 18971, Apr... only must be designed so that, during any reversal in flight, the engine will produce no more than... engine from producing more than idle thrust when the reversing system malfunctions; except that it may...

14 CFR 23.933 - Reversing systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... analysis and testing completed by the engine and propeller manufacturers. [Doc. No. 26344, 58 FR 18971, Apr... only must be designed so that, during any reversal in flight, the engine will produce no more than... engine from producing more than idle thrust when the reversing system malfunctions; except that it may...

14 CFR 23.933 - Reversing systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... analysis and testing completed by the engine and propeller manufacturers. [Doc. No. 26344, 58 FR 18971, Apr... only must be designed so that, during any reversal in flight, the engine will produce no more than... engine from producing more than idle thrust when the reversing system malfunctions; except that it may...

Stress-dependent changes in neuroinflammatory markers observed after common laboratory stressors are not seen following acute social defeat of the Sprague Dawley rat.

PubMed

Hueston, Cara M; Barnum, Christopher J; Eberle, Jaime A; Ferraioli, Frank J; Buck, Hollin M; Deak, Terrence

2011-08-03

Exposure to acute stress has been shown to increase the expression of pro-inflammatory cytokines in brain, blood and peripheral organs. However, the nature of the inflammatory response evoked by acute stress varies depending on the stressor used and species examined. The goal of the following series of studies was to characterize the consequences of social defeat in the Sprague Dawley (SD) rat using three different social defeat paradigms. In Experiments 1 and 2, adult male SD rats were exposed to a typical acute resident-intruder paradigm of social defeat (60 min) by placement into the home cage of a larger, aggressive Long Evans rat and brain tissue was collected at multiple time points for analysis of IL-1β protein and gene expression changes in the PVN, BNST and adrenal glands. In subsequent experiments, rats were exposed to once daily social defeat for 7 or 21 days (Experiment 3) or housed continuously with an aggressive partner (separated by a partition) for 7 days (Experiment 4) to assess the impact of chronic social stress on inflammatory measures. Despite the fact that social defeat produced a comparable corticosterone response as other stressors (restraint, forced swim and footshock; Experiment 5), acute social defeat did not affect inflammatory measures. A small but reliable increase in IL-1 gene expression was observed immediately after the 7th exposure to social defeat, while other inflammatory measures were unaffected. In contrast, restraint, forced swim and footshock all significantly increased IL-1 gene expression in the PVN; other inflammatory factors (IL-6, cox-2) were unaffected in this structure. These findings provide a comprehensive evaluation of stress-dependent inflammatory changes in the SD rat, raising intriguing questions regarding the features of the stress challenge that may be predictive of stress-dependent neuroinflammation. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of the Volkswagen emissions control defeat device on US public health

NASA Astrophysics Data System (ADS)

Barrett, Steven R. H.; Speth, Raymond L.; Eastham, Sebastian D.; Dedoussi, Irene C.; Ashok, Akshay; Malina, Robert; Keith, David W.

2015-11-01

The US Environmental Protection Agency (EPA) has alleged that Volkswagen Group of America (VW) violated the Clean Air Act (CAA) by developing and installing emissions control system ‘defeat devices’ (software) in model year 2009-2015 vehicles with 2.0 litre diesel engines. VW has admitted the inclusion of defeat devices. On-road emissions testing suggests that in-use NOx emissions for these vehicles are a factor of 10 to 40 above the EPA standard. In this paper we quantify the human health impacts and associated costs of the excess emissions. We propagate uncertainties throughout the analysis. A distribution function for excess emissions is estimated based on available in-use NOx emissions measurements. We then use vehicle sales data and the STEP vehicle fleet model to estimate vehicle distance traveled per year for the fleet. The excess NOx emissions are allocated on a 50 km grid using an EPA estimate of the light duty diesel vehicle NOx emissions distribution. We apply a GEOS-Chem adjoint-based rapid air pollution exposure model to produce estimates of particulate matter and ozone exposure due to the spatially resolved excess NOx emissions. A set of concentration-response functions is applied to estimate mortality and morbidity outcomes. Integrated over the sales period (2008-2015) we estimate that the excess emissions will cause 59 (95% CI: 10 to 150) early deaths in the US. When monetizing premature mortality using EPA-recommended data, we find a social cost of ˜450m over the sales period. For the current fleet, we estimate that a return to compliance for all affected vehicles by the end of 2016 will avert ˜130 early deaths and avoid ˜840m in social costs compared to a counterfactual case without recall.

Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance.

PubMed

Ramirez, Karol; Shea, Daniel T; McKim, Daniel B; Reader, Brenda F; Sheridan, John F

2015-05-01

Psychosocial stress is associated with altered immunity, anxiety and depression. Previously we showed that repeated social defeat (RSD) promoted microglia activation and social avoidance behavior that persisted for 24days after cessation of RSD. The aim of the present study was to determine if imipramine (a tricyclic antidepressant) would reverse RSD-inducedsocial avoidance and ameliorate neuroinflammatory responses. To test this, C57BL/6 mice were divided into treatment groups. One group from RSD and controls received daily injections of imipramine for 24days, following 6 cycles of RSD. Two other groups were treated with saline. RSD mice spent significantly less time in the interaction zone when an aggressor was present in the cage. Administration of imipramine reversed social avoidance behavior, significantly increasing the interaction time, so that it was similar to that of control mice. Moreover, 24days of imipramine treatment in RSD mice significantly decreased stress-induced mRNA levels for IL-6 in brain microglia. Following ex vivo LPS stimulation, microglia from mice exposed to RSD, had higher mRNA expression of IL-6, TNF-α, and IL-1β, and this was reversed by imipramine treatment. In a second experiment, imipramine was added to drinking water confirming the reversal of social avoidant behavior and decrease in mRNA expression of IL-6 in microglia. These data suggest that the antidepressant imipramine may exert its effect, in part, by down-regulating microglial activation. Copyright © 2015 Elsevier Inc. All rights reserved.

Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance

PubMed Central

Ramirez, Karol; Shea, Daniel T.; McKim, Daniel B.; B.F., Reader; Sheridan, John F.

2015-01-01

Psychosocial stress is associated with altered immunity, anxiety and depression. Previously we showed that repeated social defeat (RSD) promoted microglia activation and social avoidance behavior that persisted for 24 days after cessation of RSD. The aim of the present study was to determine if imipramine (a tricyclic antidepressant) would reverse RSD-induced social avoidance and ameliorate neuroinflammatory responses. To test this, C57BL/6 mice were divided into treatment groups. One group from RSD and controls received daily injections of imipramine for 24 days, following 6 cycles of RSD. Two other groups were treated with saline. RSD mice spent significantly less time in the interaction zone when an aggressor was present in the cage. Administration of imipramine reversed social avoidance behavior, significantly increasing the interaction time, so that it was similar to that of control mice. Moreover, 24 days of imipramine treatment in RSD mice significantly decreased stress-induced mRNA levels for IL-6 in brain microglia. Following ex vivo LPS stimulation, microglia from mice exposed to RSD, had higher mRNA expression of IL-6, TNF-α, and IL-1β, and this was reversed by imipramine treatment. In a second experiment, imipramine was added to drinking water confirming the reversal of social avoidant behavior and decrease in mRNA expression of IL-6 in microglia. These data suggest that the antidepressant imipramine may exert its effect, in part, by down-regulating microglial activation. PMID:25701613

Plan Colombia: A Case For Political Warfare To Defeat Transnational Criminal Organizations In The Gray Zone

DTIC Science & Technology

2016-05-26

Approved for public release; distribution is unlimited Plan Colombia: A Case for Political Warfare to Defeat Transnational Criminal Organizations ...to Defeat Transitional Criminal Organizations 5a. CONTRACT NUMBER in the Gray Zone 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...NUMBER 6. AUTHOR(S) MAJ Kyle M. Spade 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION

How Bacterial Population Soliton Waves Can Defeat a Funnel Ring

NASA Astrophysics Data System (ADS)

Austin, Robert; Morris, Ryan; Phan, Average; Black, Matthew; Lin, Ke-Chih; Bos, Julia

We have constructed using microfabrication a circular corral for bacteria made of rings of concentric funnels which channel motile bacteria outwards via non-hydrodynamic interactions with the funnel walls. Although initially bacteria do move rapidly outwards with the funnels, they are able with increasing cell density on the perimeter to defeat the physical constraints of the funnel by launching collective, soliton like waves of bacteria inwards against the funnel ring. We present the basic data and some non-linear modeling which can explain the basic way that bacterial population solitons propagate across a funnel landscape. There are three surprising aspects to the experiments: (1) The bifurcation of the population into motile bacteria which are pumped by the funnels and bacteria which are non-motile (i.e., not pumped); (2) The launching of a collective wave which rapidly circles the device and radiates inwards against the pumping action of the funnel; (3) the subsequent loss of motility by all the bacteria after this burst of very high motility. Engineering and Physical Sciences Research Council [EP/J007404/1], National Cancer Institute (Grant No U54CA143803), and NSF PoLS program NSF PHY1521553.

Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice

PubMed Central

Martin, Vincent; Allaïli, Najib; Euvrard, Marine; Marday, Tevrasamy; Riffaud, Armance; Franc, Bernard; Mocaër, Elisabeth; Gabriel, Cecilia; Fossati, Philippe; Lehericy, Stéphane; Lanfumey, Laurence

2017-01-01

Chronic stress is known to induce not only anxiety and depressive-like phenotypes in mice but also cognitive impairments, for which the action of classical antidepressant compounds remains unsatisfactory. In this context, we investigated the effects of chronic social defeat stress (CSDS) on anxiety-, social- and cognitive-related behaviors, as well as hippocampal Bdnf, synaptic plasticity markers (PSD-95, Synaptophysin, Spinophilin, Synapsin I and MAP-2), and epigenetic modifying enzymes (MYST2, HDAC2, HDAC6, MLL3, KDM5B, DNMT3B, GADD45B) gene expression in C57BL/6J mice. CSDS for 10 days provoked long-lasting anxious-like phenotype in the open field and episodic memory deficits in the novel object recognition test. While total Bdnf mRNA level was unchanged, Bdnf exon IV, MAP-2, HDAC2, HDAC6 and MLL3 gene expression was significantly decreased in the CSDS mouse hippocampus. In CSDS mice treated 3 weeks with 50 mg/kg/d agomelatine, an antidepressant with melatonergic receptor agonist and 5-HT2C receptor antagonist properties, the anxious-like phenotype was not reversed, but the treatment successfully prevented the cognitive impairments and hippocampal gene expression modifications. Altogether, these data evidenced that, in mice, agomelatine was effective in alleviating stress-induced altered cognitive functions, possibly through a mechanism involving BDNF signaling, synaptic plasticity and epigenetic remodeling. PMID:28374847

Escalated cocaine "binges" in rats: enduring effects of social defeat stress or intra-VTA CRF.

PubMed

Leonard, Michael Z; DeBold, Joseph F; Miczek, Klaus A

2017-09-01

Exposure to intermittent social defeat stress elicits corticotropin releasing factor (CRF) release into the VTA and induces long-term modulation of mesocorticolimbic dopamine activity in rats. These adaptations are associated with an intense cocaine-taking phenotype, which is prevented by CRF receptor antagonists. The present studies examine whether infusion of CRF into the VTA is sufficient to escalate cocaine-taking behavior, in the absence of social defeat experience. Additionally, we aimed to characterize changes in cocaine valuation that may promote binge-like cocaine intake. Male Long-Evans rats were microinjected into the VTA with CRF (50 or 500 ng/side), vehicle, or subjected to social defeat stress, intermittently over 10 days. Animals were then trained to self-administer IV cocaine (FR5). Economic demand for cocaine was evaluated using a within-session behavioral-economics threshold procedure, which was followed by a 24-h extended access "binge." Rats that experienced social defeat or received intra-VTA CRF microinfusions (50 ng) both took significantly more cocaine than controls over the 24-h binge but showed distinct patterns of intake. Behavioral economic analysis revealed that individual demand for cocaine strongly predicts binge-like consumption, and demand elasticity (i.e. α) is augmented by intra-VTA CRF, but not by social defeat. The effects of CRF on cocaine-taking were also prevented by intra-VTA pretreatment with CP376395, but not Astressin-2B. Repeated infusion of CRF into the VTA persistently alters cocaine valuation and intensifies binge-like drug intake in a CRF-R1-dependent manner. Conversely, the persistent pattern of cocaine bingeing induced by social defeat stress may suggest impaired inhibitory control, independent of reward valuation.

Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system.

PubMed

Montagud-Romero, Sandra; Nuñez, Cristina; Blanco-Gandia, M Carmen; Martínez-Laorden, Elena; Aguilar, María A; Navarro-Zaragoza, Javier; Almela, Pilar; Milanés, Maria-Victoria; Laorden, María-Luisa; Miñarro, José; Rodríguez-Arias, Marta

2017-07-01

Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice. Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine. In a second set of mice, the expressions of the abovementioned dopaminergic and proBDNF and TrkB receptor were measured in VTA and NAc, respectively. Adolescent mice experienced social defeats less intensely than their adult counterparts and produced lower levels of corticosterone. However, both adult and adolescent defeated mice developed conditioned place preference for the compartment associated with this low dose of cocaine. Furthermore, only adolescent defeated mice displayed diminished levels of the transcription factors Pitx3 in the VTA, without changes in the expression of DAT and D2DR in the NAc. In addition, stressed adult mice showed a decreased expression of proBDNF and the TrkB receptor, while stressed adolescent mice exhibited increased expression of latter without changes in the former. Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.

Role of dopamine neurotransmission in the long-term effects of repeated social defeat on the conditioned rewarding effects of cocaine.

PubMed

Montagud-Romero, S; Reguilon, M D; Roger-Sanchez, C; Pascual, M; Aguilar, M A; Guerri, C; Miñarro, J; Rodríguez-Arias, M

2016-11-03

Numerous studies report that social defeat stress alters dopamine (DA) neurotransmission in several areas of the brain. Alterations of the mesolimbic dopaminergic pathway are believed to be responsible for the increased vulnerability to drug use observed as a result of social stress. In the present study, we evaluated the influence of DA receptors on the long-term effect of repeated social defeat (RSD) on the conditioned rewarding and reinstating effects of cocaine. For this purpose, the D1R antagonist SCH 23390 and the D1R antagonist raclopride were administered 30min before each social defeat and a cocaine-induced CPP procedure was initiated three weeks later. The expression of the D1R and D2R was also measured in the cortex and hippocampus throughout the entire procedure. Mice exposed to RSD showed an increase in the conditioned rewarding effects of cocaine that was blocked by both DA receptors antagonists when a subthreshold dose of cocaine was employed. However, while the vulnerability to reinstatement of the preference induced by 25mg/kg cocaine-induced CPP was abolished by the D1R antagonist, it was practically unaffected by raclopride. Increases in D2R receptor levels were observed in the cortex of defeated animals after the first and fourth social defeats and in the hippocampus 3weeks later. Nevertheless, D1R receptor levels in the hippocampus decreased only after the last social defeat. Our results confirm that RSD enhances the conditioned rewarding effects of cocaine and that both DA receptors are involved in this enduring effect of social stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress.

PubMed

Weber, Matthew A; Graack, Eric T; Scholl, Jamie L; Renner, Kenneth J; Forster, Gina L; Watt, Michael J

2018-06-14

Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague-Dawley rats exposed to social defeat in mid-adolescence (P35-39) show impaired working memory in adulthood (P56-70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter-mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor-mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction. Control and previously defeated rats did not differ in either DOPA accumulation following amino acid decarboxylase inhibition (NSD-1015 100 mg/kg ip.) or total/phosphorylated tyrosine hydroxylase protein expression, suggesting dopamine synthesis in the adult mPFC is not altered by adolescent defeat. However, exposure to adolescent defeat caused greater decreases in extracellular dopamine release (measured using in vivo chronoamperometry) in the adult mPFC upon local infusion of the D2 receptor agonist quinpirole (3 nM), implying greater D2 autoreceptor function. Equally enhanced D2 autoreceptor-mediated inhibition of dopamine release is seen in the adolescent (P40 or P49) mPFC, which declines in control rats by adulthood. However, this developmental decrease in autoreceptor function is absent following adolescent defeat, suggesting retention of an adolescent-like phenotype into adulthood. Current and previous findings indicate adolescent defeat decreases extracellular dopamine availability in the adult mPFC via both enhanced inhibition of dopamine release and increased dopamine clearance, which may be viable targets for improving treatment of cognitive deficits seen in neuropsychiatric disorders promoted by adolescent stress. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cortical functional hyperconnectivity in a mouse model of depression and selective network effects of ketamine.

PubMed

McGirr, Alexander; LeDue, Jeffrey; Chan, Allen W; Xie, Yicheng; Murphy, Timothy H

2017-08-01

See Huang and Liston (doi:10.1093/awx166) for a scientific commentary on this article.Human depression is associated with glutamatergic dysfunction and alterations in resting state network activity. However, the indirect nature of human in vivo glutamate and activity assessments obscures mechanistic details. Using the chronic social defeat mouse model of depression, we determine how mesoscale glutamatergic networks are altered after chronic stress, and in response to the rapid acting antidepressant, ketamine. Transgenic mice (Ai85) expressing iGluSnFR (a recombinant protein sensor) permitted real-time in vivo selective characterization of extracellular glutamate and longitudinal imaging of mesoscale cortical glutamatergic functional circuits. Mice underwent chronic social defeat or a control condition, while spontaneous cortical activity was longitudinally sampled. After chronic social defeat, we observed network-wide glutamate functional hyperconnectivity in defeated animals, which was confirmed with voltage sensitive dye imaging in an independent cohort. Subanaesthetic ketamine has unique effects in defeated animals. Acutely, subanaesthetic ketamine induces large global cortical glutamate transients in defeated animals, and an elevated subanaesthetic dose resulted in sustained global increase in cortical glutamate. Local cortical inhibition of glutamate transporters in naïve mice given ketamine produced a similar extracellular glutamate phenotype, with both glutamate transients and a dose-dependent accumulation of glutamate. Twenty-four hours after ketamine, normalization of depressive-like behaviour in defeated animals was accompanied by reduced glutamate functional connectivity strength. Altered glutamate functional connectivity in this animal model confirms the central role of glutamate dynamics as well as network-wide changes after chronic stress and in response to ketamine. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

5-Hydroxytryptamine-Independent Antidepressant Actions of (R)-Ketamine in a Chronic Social Defeat Stress Model.

PubMed

Zhang, Kai; Dong, Chao; Fujita, Yuko; Fujita, Atsuhiro; Hashimoto, Kenji

2018-02-01

Previous reports suggest that 5-hydroxytryptamine might play a role in the antidepressant actions of (R,S)-ketamine. However, its role in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, is unknown. This study was conducted to examine whether 5-hydroxytryptamine depletion affects the antidepressant actions of (R)-ketamine in a chronic social defeat stress model. An inhibitor of 5-hydroxytryptamine synthesis, para-chlorophenylalanine methyl ester hydrochloride (300 mg/kg, twice daily for 3 consecutive days), or vehicle was administered to control and chronic social defeat stress-susceptible mice. Levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, in mouse brain regions were measured using high-performance liquid chromatography. Furthermore, antidepressant effects of (R)-ketamine (10 mg/kg) in the vehicle- and para-chlorophenylalanine methyl ester hydrochloride-treated susceptible mice were assessed using tail suspension test and 1% sucrose preference test. para-Chlorophenylalanine methyl ester hydrochloride treatment caused marked reductions of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the brain regions of control and chronic social defeat stress susceptible mice. In the tail suspension test, (R)-ketamine significantly attenuated the increased immobility time in the chronic social defeat stress-susceptible mice with or without 5-hydroxytryptamine depletion. In the sucrose preference test (2 and 5 days after a single dose), (R)-ketamine significantly enhanced reduced sucrose consumption in the chronic social defeat stress-susceptible mice with or without 5-hydroxytryptamine depletion. These findings show that 5-hydroxytryptamine depletion did not affect the antidepressant effects of (R)-ketamine in a chronic social defeat stress model. Therefore, it is unlikely that 5-hydroxytryptamine plays a major role in the antidepressant actions of (R)-ketamine. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

PubMed Central

Burke, Andrew R.; Watt, Michael J.; Forster, Gina L.

2011-01-01

Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc) and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence. PMID:21933700

Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood.

PubMed

Novick, Andrew M; Mears, Mackenzie; Forster, Gina L; Lei, Yanlin; Tejani-Butt, Shanaz M; Watt, Michael J

2016-05-01

Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-D-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing toward the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: Prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence

PubMed Central

Burke, Andrew R.; DeBold, Joseph F.; Miczek, Klaus A.

2016-01-01

Background Activation of corticotropin releasing factor type 1 receptors (CRF-R1) in the ventral tegmental area (VTA) represents a critical mechanism for social defeat to escalate cocaine self-administration in adult rats. Objective We determined the acute effect of a CRF-R1 antagonist (CP376395) microinfusion into the VTA prior to each episode of social defeat in adolescent rats and determined whether this drug treatment could prevent later escalation of cocaine taking in early adulthood. Methods Rats were implanted with bilateral cannulae aimed at the VTA five days before the first social defeat. Bilateral microinfusion of CP376395 (500ng/side) or vehicle occurred 20 min before each episode of social defeat on postnatal days (P) 35, 38, 41, and 44. Behavior was quantified on P35 and P44. On P57, rats were implanted with intra-jugular catheters, and subsequent cocaine self-administration was analyzed. Results CP376395-treated adolescent rats walked less and were attacked more slowly, but were socially investigated more than vehicle-treated adolescents. Vehicle-treated rats showed increased social and decreased non-social exploration from P35 to P44, while CP376395-treated rats did not. Socially defeated, vehicle-treated adolescents took more cocaine during a 24-hour unlimited access binge during adulthood. The latency to supine posture on P44 was inversely correlated with later cocaine self-administration during fixed and progressive ratio schedules of reinforcement and during the binge. Conclusions CP376395 treatment in adolescence blocked escalation of cocaine taking in adulthood. Episodes of social defeat stress engender neuroadaptation in CRF-R1s in the VTA that alter coping with social stress and that persist into adulthood. PMID:27251131

Sex differences in stress-induced social withdrawal: independence from adult gonadal hormones and inhibition of female phenotype by corncob bedding.

PubMed

Trainor, Brian C; Takahashi, Elizabeth Y; Campi, Katharine L; Florez, Stefani A; Greenberg, Gian D; Laman-Maharg, Abigail; Laredo, Sarah A; Orr, Veronica N; Silva, Andrea L; Steinman, Michael Q

2013-03-01

There is compelling evidence for important sex differences in behavioral and hormonal responses to psychosocial stress. Here we examined the effects of gonadal hormones on behavioral responses to social defeat stress in monogamous California mice (Peromyscus californicus). Three episodes of social defeat induced social withdrawal in intact females but not males. Gonadectomy blocked corticosterone responses to defeat in females and sensitized male corticosterone responses. However, gonadectomy had no effects on social interaction behavior, suggesting that social withdrawal is not dependent on gonadal hormones in the adult California mouse. In contrast, defeat reduced exploratory behavior in the open field test for intact but not castrated males. We also examined the effects of social defeat on social interaction behavior when California mice were raised on corncob bedding, which has estrogenic properties. In this dataset of over 300 mice, we observed that social defeat did not induce social withdrawal when females were raised on corncob bedding. This finding suggests that the use of corncob in rodent studies could mask important sex differences in the effects of stress on brain and behavior. Although gonadal hormones do not affect social withdrawal behavior in adults, our data suggest that hormones may act earlier in development to induce a more resilient social phenotype. Copyright © 2013 Elsevier Inc. All rights reserved.

Activation of kappa opioid receptors in the dorsal raphe have sex dependent effects on social behavior in California mice.

PubMed

Wright, Emily C; Parks, Tiffany V; Alexander, Jonathon O; Supra, Rajesh; Trainor, Brian C

2018-06-06

Kappa opioid receptor activation has been linked to stress and anxiety behavior, thus leading to kappa antagonists being popularized in research as potential anxiolytics. However, while these findings may hold true in standard models, the neuromodulatory effects of social defeat may change the behavioral outcome of kappa opioid receptor activation. Previous research has shown that social defeat can lead to hyperactivity of serotonergic neurons in the dorsal raphe nucleus, and that inhibition of this increase blocks the social deficits caused by defeat. Kappa opioid receptor activation in the dorsal raphe nucleus works to decrease serotonergic activity. We injected the kappa opioid receptor U50,488 directly into the dorsal raphe nucleus of male and female, defeat and control adult California mice. Here we show evidence that U50,488 induces anxiety behavior in control male California mice, but helps relieve it in defeated males. Consistent with previous literature, we find little effect in females adding evidence that there are marked and important sex differences in the kappa opioid system. Copyright © 2018 Elsevier B.V. All rights reserved.

A single social defeat reduces aggression in a highly aggressive strain of Drosophila

PubMed Central

Penn, Jill K. M.; Zito, Michael F.; Kravitz, Edward A.

2010-01-01

Genes and prior experience both influence the behavior of animals, but the relative contribution of each to fighting behavior in Drosophila remains unclear. To address this issue, we bred hyperaggressive flies by selecting winners of fights over 34–37 generations. Males of this strain initiate fights sooner, retaliate more often, and regularly defeat opponents from the nonselected parent Canton-S strain. After a defeat, however, these highly aggressive flies lose their second fights against socially naïve counterparts. Defeated flies also lunge and retaliate less after experiencing a loss, suggesting that the subsequent losses result from flies becoming less aggressive. Remarkably, flies that were once capable of engaging in high-intensity boxing and tussling patterns of behavior for extended periods of time often do not even engage in mid-intensity lunging after a single defeat. Furthermore, these formerly highly aggressive flies lose all competitive advantage over nonselected Canton-S after experiencing a loss. Lastly, females were more likely to copulate with males from the nonselected parent line than with the hyperaggressive strain. PMID:20616023

14 CFR 25.933 - Reversing systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... kind of failure is extremely remote. (3) Each system must have means to prevent the engine from... alone, under the most critical reversing condition expected in operation. (b) For propeller reversing...

14 CFR 25.933 - Reversing systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... kind of failure is extremely remote. (3) Each system must have means to prevent the engine from... alone, under the most critical reversing condition expected in operation. (b) For propeller reversing...

14 CFR 25.933 - Reversing systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... kind of failure is extremely remote. (3) Each system must have means to prevent the engine from... alone, under the most critical reversing condition expected in operation. (b) For propeller reversing...

ALS Association

MedlinePlus

... toward a world without ALS! Walk to Defeat ALS® Walk to Defeat ALS® draws people of all ... We need your help. I Will Advocate National ALS Registry The National ALS Registry is a congressionally ...

DIC-CAM recipe for reverse engineering

NASA Astrophysics Data System (ADS)

Romero-Carrillo, P.; Lopez-Alba, E.; Dorado, R.; Diaz-Garrido, F. A.

2012-04-01

Reverse engineering (RE) tries to model and manufacture an object from measurements one of a reference object. Modern optical measurement systems and computer aided engineering software have improved reverse engineering procedures. We detail the main RE steps from 3D digitalization by Digital Image Correlation to manufacturing. The previous description is complemented with an application example, which portrays the performance of RE. The differences between original and manufactured objects are less than 2 mm (close to the tool radius).

Flight Measurements of the Effect of a Controllable Thrust Reverser on the Flight Characteristics of a Single-Engine Jet Airplane

NASA Technical Reports Server (NTRS)

Anderson, Seth B.; Cooper, George E.; Faye, Alan E., Jr.

1959-01-01

A flight investigation was undertaken to determine the effect of a fully controllable thrust reverser on the flight characteristics of a single-engine jet airplane. Tests were made using a cylindrical target-type reverser actuated by a hydraulic cylinder through a "beep-type" cockpit control mounted at the base of the throttle. The thrust reverser was evaluated as an in-flight decelerating device, as a flight path control and airspeed control in landing approach, and as a braking device during the ground roll. Full deflection of the reverser for one reverser configuration resulted in a reverse thrust ratio of as much as 85 percent, which at maximum engine power corresponded to a reversed thrust of 5100 pounds. Use of the reverser in landing approach made possible a wide selection of approach angles, a large reduction in approach speed at steep approach angles, improved control of flight path angle, and more accuracy in hitting a given touchdown point. The use of the reverser as a speed brake at lower airspeeds was compromised by a longitudinal trim change. At the lower airspeeds and higher engine powers there was insufficient elevator power to overcome the nose-down trim change at full reverser deflection.

40 CFR 86.004-16 - Prohibition of defeat devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... exceptions set forth in the definition of “defeat device” in § 86.004-2 has been met. (2) Information... evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies...

40 CFR 86.004-16 - Prohibition of defeat devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... exceptions set forth in the definition of “defeat device” in § 86.004-2 has been met. (2) Information... evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies...

Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.

PubMed

Montagud-Romero, S; Aguilar, M A; Maldonado, C; Manzanedo, C; Miñarro, J; Rodríguez-Arias, M

2015-08-01

Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute social defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1mg/kg or 25mg/kg of cocaine. The effects of social defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25mg/kg. Adult mice exposed to social defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of social defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced. Copyright © 2015 Elsevier Inc. All rights reserved.

Engineering Encounters: Reverse Engineering

ERIC Educational Resources Information Center

McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

2017-01-01

This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests: A model for reward pathology with effects of agomelatine.

PubMed

Bergamini, Giorgio; Cathomas, Flurin; Auer, Sandra; Sigrist, Hannes; Seifritz, Erich; Patterson, Michael; Gabriel, Cecilia; Pryce, Christopher R

2016-09-01

A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Adolescent social defeat alters markers of adult dopaminergic function.

PubMed

Novick, Andrew M; Forster, Gina L; Tejani-Butt, Shanaz M; Watt, Michael J

2011-08-10

Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [(3)H]-GBR12935 binding to the dopamine transporter and [(3)H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult dopamine system, which may contribute to behavioral alterations and increased drug seeking. Copyright © 2011 Elsevier Inc. All rights reserved.

The Significance of the Bulgarian Senior Military Leadership in World War I: A Comparative Study of the Bulgarian Army Operations at Dobro Pole and Doiran in 1918

DTIC Science & Technology

2012-06-08

the 9th Infantry (Pleven) Division under the command of General Ivan Vazov not only defeated the combined British, French , and Greek offensive at...of General Ivan Vazov not only defeated the combined British, French , and Greek offensive at Doiran, but also created the conditions for what might...Pleven) Division in particular, not only defeated the joint British, French , and Greek offensive at Doiran, but also created the 2 conditions

Advanced dexterous manipulation for IED defeat : report on the feasibility of using the ShadowHand for remote operations.

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

Anderson, Robert J.

2011-01-01

Improvised Explosive Device (IED) defeat (IEDD) operations can involve intricate operations that exceed the current capabilities of the grippers on board current bombsquad robots. The Shadow Dexterous Hand from the Shadow Robot Company or 'ShadowHand' for short (www.shadowrobot.com) is the first commercially available robot hand that realistically replicates the motion, degrees-of-freedom and dimensions of a human hand (Figure 1). In this study we evaluate the potential for the ShadowHand to perform potential IED defeat tasks on a mobile platform.

Social skills of persons with self-defeating personality.

PubMed

Schill, T

1995-10-01

55 undergraduate men and 55 women took Schill's 1990 Self-defeating Personality Scale and Lorr, Youniss, and Stefic's (1991) multidimensional Social Relations Survey. As expected, persons who endorsed more self-defeating characteristics scored lower on scales which make up the Social Skills or Assertiveness Factor. However, these scores did not have significant correlations with the Empathy or Social Approval Need Scales; two of the three scales which make up the Empathy Factor. The results were discussed in terms of prior work relating deficits in social skills to dysfunctional early parenting.

A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

PubMed

Floares, Alexandru George

2008-01-01

Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

Losing without Fighting - Simple Aversive Stimulation Induces Submissiveness Typical for Social Defeat via the Action of Nitric Oxide, but Only When Preceded by an Aggression Priming Stimulus

PubMed Central

Rillich, Jan; Stevenson, Paul A.

2017-01-01

Losing a fight (social defeat) induces submissiveness and behavioral depression in many animals, but the mechanisms are unclear. Here we investigate how the social defeat syndrome can be established as a result of experiencing aversive stimuli and the roles of neuromodulators in the process. While biogenic amines and nitric oxide (NO) are associated with reduced aggression in mammals and insects, their specific actions during conflict are unknown. Although the social defeat syndrome normally results from complex interactions, we could induce it in male crickets simply by applying aversive stimuli (AS) in an aggressive context. Aggressive crickets became immediately submissive and behaved like losers after experiencing two brief AS (light wind puffs to the cerci), but only when preceded by a priming stimulus (PS, stroking the antenna with another male antenna). Notably, submissiveness was not induced when the PS preceded the AS by more than 1 min, or when the PS followed the AS, or using a female antenna as the preceding stimulus. These findings suggest that any potentially detrimental stimulus can acquire the attribute of an aversive agonistic signal when experienced in an aggressive context. Crickets, it seems, need only to evaluate their net sensory impact rather than the qualities of a variety of complex agonistic signals. Selective drug treatments revealed that NO, but not serotonin, dopamine or octopamine, is necessary to establish the submissive status following pairing of the priming and aversive stimuli. Moreover, treatment with an NO donor also induced the social defeat syndrome, but only when combined with the PS. This confirms our hypothesis that aversive agonistic experiences accumulated by crickets during fighting invoke social defeat via the action of NO and illustrates that a relatively simple mechanism underlies the seemingly complex social decision to flee. The simple stimulus regime described here for inducing social defeat opens new avenues for investigating the cellular control of subordinate behavior and post-conflict depression. PMID:28381994

Differential long-term effects of social stress during adolescence on anxiety in Wistar and wild-type rats.

PubMed

Vidal, Jose; Buwalda, Bauke; Koolhaas, Jaap M

2011-06-01

Severe and chronic stress may interfere with adolescent neuronal plasticity that turns the juvenile brain into an adult brain increasing the vulnerability to develop anxiety disorders. It is well-known from adult stress research that there is a large individual differentiation in stress vulnerability. The current study is aimed at the individual resilience and vulnerability to adolescent social stress. Two strains of rats that differ in social behavioral skills were subjected to social stress during adolescence. In three experiments we studied short and long term effects of adolescent social stress using a water conflict test in different contexts. Wistar rats which had been socially defeated on postnatal days 45 and 46 showed, following water deprivation, a strong decrease in the total amount of water consumed and time spent drinking when tested 2 days and 3 weeks later in the context where they received the defeat experience. Also a strong increase in drinking latency was noticed in the context of the previous defeat. No differences in these parameters were found between defeated and non-defeated wild-type rats. The results of the water conflict test in an environment where no association with the previous defeat experience was present showed that the adolescent social stress did not induce a generalized anxiety. In conclusion, the water conflict test is a useful tool to measure the influence of social defeat on the motivation to obtain resources under conditions with different stimulus properties. In addition, our data suggest the importance of the strain used in adolescent stress experiments. The fact that Wistar rats showed a strong association with the context at adulthood whereas no effect was observed in the wild-type rats shows that victim characteristics are important determining factors for the long term effects of adolescent social stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Un-Building Blocks: A Model of Reverse Engineering and Applicable Heuristics

DTIC Science & Technology

2015-12-01

CONCLUSIONS The machine does not isolate man from the great problems of nature but plunges him more deeply into them. Antoine de Saint-Exupery— Wind ...DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Reverse engineering is the problem -solving activity that ensues when one takes a...Douglas Moses, Vice Provost for Academic Affairs iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT Reverse engineering is the problem -solving

Reverse engineering of aircraft wing data using a partial differential equation surface model

NASA Astrophysics Data System (ADS)

Huband, Jacalyn Mann

Reverse engineering is a multi-step process used in industry to determine a production representation of an existing physical object. This representation is in the form of mathematical equations that are compatible with computer-aided design and computer-aided manufacturing (CAD/CAM) equipment. The four basic steps to the reverse engineering process are data acquisition, data separation, surface or curve fitting, and CAD/CAM production. The surface fitting step determines the design representation of the object, and thus is critical to the success or failure of the reverse engineering process. Although surface fitting methods described in the literature are used to model a variety of surfaces, they are not suitable for reversing aircraft wings. In this dissertation, we develop and demonstrate a new strategy for reversing a mathematical representation of an aircraft wing. The basis of our strategy is to take an aircraft design model and determine if an inverse model can be derived. A candidate design model for this research is the partial differential equation (PDE) surface model, proposed by Bloor and Wilson and used in the Rapid Airplane Parameter Input Design (RAPID) tool at the NASA-LaRC Geolab. There are several basic mathematical problems involved in reversing the PDE surface model: (i) deriving a computational approximation of the surface function; (ii) determining a radial parametrization of the wing; (iii) choosing mathematical models or classes of functions for representation of the boundary functions; (iv) fitting the boundary data points by the chosen boundary functions; and (v) simultaneously solving for the axial parameterization and the derivative boundary functions. The study of the techniques to solve the above mathematical problems has culminated in a reverse PDE surface model and two reverse PDE surface algorithms. One reverse PDE surface algorithm recovers engineering design parameters for the RAPID tool from aircraft wing data and the other generates a PDE surface model with spline boundary functions from an arbitrary set of grid points. Our numerical tests show that the reverse PDE surface model and the reverse PDE surface algorithms can be used for the reverse engineering of aircraft wing data.

Social stress models in depression research: what do they tell us?

PubMed Central

Chaouloff, Francis

2013-01-01

There has been a recent surge of interest in the use of social stress models, especially social defeat. Such an interest lies both on the recognition that stressors of social origin play a major role in human psychopathologies and on the acknowledgement that natural and hence ethologically-based stress models bear important translational value. The use of the most recent technology has allowed the recognition of the mechanisms through which social defeat may have enduring psychoneuroendocrine effects, especially social avoidance and anhedonia, two behaviours relevant to human depression. Taken with the sensitivity of these behavioural outcomes to repeated antidepressant treatments, it has been proposed that the social defeat model might be an animal model of depression. The present survey is aimed at examining the limits of such an interpretation, focusing on methodological aspects and on the relevance of social defeat to the study of anxiety-related pathologies. PMID:23532563

Subscale testing of prompt agent defeat formulations

NASA Astrophysics Data System (ADS)

Knott, A.; Stamatis, D.; Svingala, F.; Lightstone, J.; Miller, K.; Bensman, M.; Bohmke, M.

2017-01-01

There is a need to improve the current bioagent defeat systems with formulations that produce lower peak pressure and impulse, sustained high temperatures, and release of biocidal species for prompt defeat applications. In this work, explosive charge configurations similar to fuel-air explosives were detonated in a semi-enclosed chamber configuration. Binder type and fuel-to-oxidizer ratios were varied to observe the effects on combustion performance. Thermocouple measurements and high-speed video were used to monitor the combustion of the dispersed formulation. The down-selected formulations were then tested in a sub-scale vented agent defeat system developed to evaluate performance of formulations against aerosolized Bacillus thuringiensis (Bt) spores. Diagnostics including thermocouples and piezoelectric pressure gauges were utilized to characterize the detonation event. Biological sampling with surface coupons, liquid impingement, and filters of the post detonation environment were utilized to determine spore survivability and to rank the relative effectiveness of each formulation.

14 CFR 33.97 - Thrust reversers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Thrust reversers. 33.97 Section 33.97 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If the...

14 CFR 33.97 - Thrust reversers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Thrust reversers. 33.97 Section 33.97 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If the...

14 CFR 33.97 - Thrust reversers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Thrust reversers. 33.97 Section 33.97 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If the...

14 CFR 33.97 - Thrust reversers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If the... this subpart must be run with the reverser installed. In complying with this section, the power control... regimes of control operations are incorporated necessitating scheduling of the power-control lever motion...

14 CFR 33.97 - Thrust reversers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If the... this subpart must be run with the reverser installed. In complying with this section, the power control... regimes of control operations are incorporated necessitating scheduling of the power-control lever motion...

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian Hamsters

PubMed Central

Clinard, Catherine T.; Barnes, Abigail K.; Adler, Samuel G.; Cooper, Matthew A.

2016-01-01

Winning aggressive disputes is one of several experiences that can alter responses to future stressful events. We have previously tested dominant and subordinate male Syrian hamsters in a conditioned defeat model and found that dominant individuals show less change in behavior following social defeat stress compared to subordinates and controls, indicating a reduced conditioned defeat response. Resistance to the effects of social defeat in dominants is experience-dependent and requires the maintenance of dominance relationships for 14 days. For this study we investigated whether winning aggressive interactions increases plasma testosterone and whether repeatedly winning increases androgen receptor expression. First, male hamsters were paired in daily 10-min aggressive encounters and blood samples were collected immediately before and 15-min and 30-min after the formation of dominance relationships. Dominants showed an increase in plasma testosterone at 15-min post-interaction compared to their pre-interaction baseline, whereas subordinates and controls showed no change in plasma testosterone. Secondly, we investigated whether 14 days of dominant social status increased androgen or estrogen alpha-receptor immunoreactivity in brain regions that regulate the conditioned defeat response. Dominants showed more androgen, but not estrogen alpha, receptor immuno-positive cells in the dorsal medial amygdala (dMeA) and ventral lateral septum (vLS) compared to subordinates and controls. Finally, we showed that one day of dominant social status was insufficient to increase androgen receptor immunoreactivity compared to subordinates. These results suggest that elevated testosterone signaling at androgen receptors in the dMeA and vLS might contribute to the reduced conditioned defeat response exhibited by dominant hamsters. PMID:27619945

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

PubMed

Liu, Yi-Yun; Zhou, Xin-Yu; Yang, Li-Ning; Wang, Hai-Yang; Zhang, Yu-Qing; Pu, Jun-Cai; Liu, Lan-Xiang; Gui, Si-Wen; Zeng, Li; Chen, Jian-Jun; Zhou, Chan-Juan; Xie, Peng

2017-01-01

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

Overlapping neurobiology of learned helplessness and conditioned defeat: Implications for PTSD and mood disorders

PubMed Central

Hammack, Sayamwong E.; Cooper, Matthew A.; Lezak, Kimberly R.

2012-01-01

Exposure to traumatic events can increase the risk for major depressive disorder (MDD) as well as posttraumatic stress disorder (PTSD), and pharmacological treatments for these disorders often involve the modulation of serotonergic (5-HT) systems. Several behavioral paradigms in rodents produce changes in behavior that resemble symptoms of MDD and these behavioral changes are sensitive to antidepressant treatments. Here we review two animal models in which MDD-like behavioral changes are elicited by exposure to an acute traumatic event during adulthood, learned helplessness (LH) and conditioned defeat. In LH, exposure of rats to inescapable, but not escapable, tailshock produces a constellation of behavioral changes that include deficits in fight/flight responding and enhanced anxiety-like behavior. In conditioned defeat, exposure of Syrian hamsters to a social defeat by a more aggressive animal leads to a loss of territorial aggression and an increase in submissive and defensive behaviors in subsequent encounters with non-aggressive conspecifics. Investigations into the neural substrates that control LH and conditioned defeat revealed that increased 5-HT activity in the dorsal raphe nucleus (DRN) is critical for both models. Other key brain regions that regulate the acquisition and/or expression of behavior in these two paradigms include the basolateral amygdala (BLA), central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST). In this review, we compare and contrast the role of each of these neural structures in mediating LH and conditioned defeat, and discuss the relevance of these data in developing a better understanding of the mechanisms underlying trauma-related depression. PMID:21396383

20 CFR 410.561c - Defeat the purpose of title IV.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Payment of Benefits § 410.561c Defeat the purpose... person from whom recovery is sought needs substantially all of his current income (including black lung...

Reverse Core Engine with Thrust Reverser

NASA Technical Reports Server (NTRS)

Chandler, Jesse M. (Inventor); Suciu, Gabriel L. (Inventor)

2017-01-01

An engine system has a gas generator, a bi-fi wall surrounding at least a portion of the gas generator, a casing surrounding a fan, and the casing having first and second thrust reverser doors which in a deployed position abut each other and the bi-fi wall.

Analysis of Ten Reverse Engineering Tools

NASA Astrophysics Data System (ADS)

Koskinen, Jussi; Lehmonen, Tero

Reverse engineering tools can be used in satisfying the information needs of software maintainers. Especially in case of maintaining large-scale legacy systems tool support is essential. Reverse engineering tools provide various kinds of capabilities to provide the needed information to the tool user. In this paper we analyze the provided capabilities in terms of four aspects: provided data structures, visualization mechanisms, information request specification mechanisms, and navigation features. We provide a compact analysis of ten representative reverse engineering tools for supporting C, C++ or Java: Eclipse Java Development Tools, Wind River Workbench (for C and C++), Understand (for C++), Imagix 4D, Creole, Javadoc, Javasrc, Source Navigator, Doxygen, and HyperSoft. The results of the study supplement the earlier findings in this important area.

Promoting Improved Ballistic Resistance of Transparent Armor

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

Wereszczak, Andrew A; Patel, P; Templeton, D W

2011-01-01

Transparent armor is a material or system of materials designed to be optically transparent, yet protect from fragmentation or ballistic impacts. Although engineered to defeat specific threats, or a range of threats, there are general requirements common to all of these designs. The primary requirement for a transparent armor system is to not only defeat the designated threat but also provide a multi-hit capability with minimized distortion of surrounding areas. Ground platforms have several parameters that must be optimized, such as weight, space efficiency, and cost versus performance. Glass exhibits tensile failure stress that is very much dependent on themore » amount of material being stressed, the side being tensile-stressed (i.e., air-versus tin-side if a float glass), and where it is being tensile stressed (i.e., in the middle or near an edge). An axiom arising from those effects is a greater amount of allowable deflection (i.e., higher failure stress) of a ballistically impacted transparent armor will result in improved ballistic resistance. Therefore, the interpretation and management of those tensile-failure-stress dependencies shall ultimately improve ballistic resistance and its predictability of transparent armor. Each of those three dependencies (size, side, and location) in a soda-lime silicate glass is described.« less

Reverse Engineering Validation using a Benchmark Synthetic Gene Circuit in Human Cells

PubMed Central

Kang, Taek; White, Jacob T.; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

2013-01-01

Multi-component biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network. PMID:23654266

Reverse engineering validation using a benchmark synthetic gene circuit in human cells.

PubMed

Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

2013-05-17

Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.

Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

PubMed

Willing, Ryan; King, Graham J W; Johnson, James A

2015-11-26

Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (p<0.001) and -14±2% (p=0.008) using commercially available, bone reverse engineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p<0.006) and -6±1% (p=0.020), and peak contact stresses increased by 75±52% (p>0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bexsero® chronicle.

PubMed

Vernikos, George; Medini, Duccio

2014-10-01

Neisseria meningitidis causes globally 1·2 million invasive disease cases and 135,000 deaths per year, mostly in infants and adolescents. A century of traditional vaccinology had failed the fight against the serogroup B meningococcus (MenB), mostly prevalent in developed countries. Eighteen years after the publication of the first complete genome sequence from a living organism, thanks to an innovative genome-based approach named 'reverse vaccinology', the first broadly effective MenB vaccine was licensed for use by the European Medical Agency and other authorities, and is being implemented worldwide. Here we review this long and passionate journey, from the disease epidemiology to novel antigen discovery, from vaccine clinical development to public health impact: two decades of scientific and technological innovation to defeat one of the most sudden and devastating invasive diseases.

The 727 airplane target thrust reverser static performance model test for refanned JT8D engines

NASA Technical Reports Server (NTRS)

Chow, C. T. P.; Atkey, E. N.

1974-01-01

The results of a scale model static performance test of target thrust reverser configurations for the Pratt and Whitney Aircraft JT8D-100 series engine are presented. The objective of the test was to select a series of suitable candidate reverser configurations for the subsequent airplane model wind tunnel ingestion and flight controls tests. Test results indicate that adequate reverse thrust performance with compatible engine airflow match is achievable for the selected configurations. Tapering of the lips results in loss of performance and only minimal flow directivity. Door pressure surveys were conducted on a selected number of lip and fence configurations to obtain data to support the design of the thrust reverser system.

Root canal debridement: an online study guide.

PubMed

2008-05-01

The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will present root canal debridement including subdivisions on canal access, canal debridement, orifice enlargement and preflaring, crown-down technique, balanced force, nickel titanium and other shape memory alloys, rotary engine-driven techniques, endodontic instruments, irrigation, electronic apex locators, sonics/ultrasonics, smear layer, and intracanal medicaments.

14 CFR 25.1305 - Powerplant instruments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... reverse pitch, for each reversing propeller. (c) For turbine engine-powered airplanes. In addition to the... required: (1) A gas temperature indicator for each engine. (2) A fuel flowmeter indicator for each engine... operated continuously but that is neither designed for continuous operation nor designed to prevent hazard...

14 CFR 25.1305 - Powerplant instruments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... reverse pitch, for each reversing propeller. (c) For turbine engine-powered airplanes. In addition to the... required: (1) A gas temperature indicator for each engine. (2) A fuel flowmeter indicator for each engine... operated continuously but that is neither designed for continuous operation nor designed to prevent hazard...

14 CFR 25.1305 - Powerplant instruments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... reverse pitch, for each reversing propeller. (c) For turbine engine-powered airplanes. In addition to the... required: (1) A gas temperature indicator for each engine. (2) A fuel flowmeter indicator for each engine... operated continuously but that is neither designed for continuous operation nor designed to prevent hazard...

14 CFR 25.1305 - Powerplant instruments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... reverse pitch, for each reversing propeller. (c) For turbine engine-powered airplanes. In addition to the... required: (1) A gas temperature indicator for each engine. (2) A fuel flowmeter indicator for each engine... operated continuously but that is neither designed for continuous operation nor designed to prevent hazard...

14 CFR 25.1305 - Powerplant instruments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... reverse pitch, for each reversing propeller. (c) For turbine engine-powered airplanes. In addition to the... required: (1) A gas temperature indicator for each engine. (2) A fuel flowmeter indicator for each engine... operated continuously but that is neither designed for continuous operation nor designed to prevent hazard...

Conditions Influencing Faculty Voting in Collective Bargaining Elections.

ERIC Educational Resources Information Center

Bornheimer, Deane G.

1985-01-01

The factors that influenced voting behavior in two faculty union defeats at New York University are examined. The importance of the swing votes cast in a run-off election by the members of a previously defeated third party is discussed. (Author/MLW)

Reverse engineering and identification in systems biology: strategies, perspectives and challenges.

PubMed

Villaverde, Alejandro F; Banga, Julio R

2014-02-06

The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology?

`Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine.

PubMed

Montagud-Romero, S; Montesinos, J; Pascual, M; Aguilar, M A; Roger-Sanchez, C; Guerri, C; Miñarro, J; Rodríguez-Arias, M

2016-10-03

Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, while there was an increase of HAT and a decrease of HDAC levels in the cortex. Three weeks after the last defeat, mice displayed an increase in histone H4(K12) acetylation and an upregulation of histone acetyl transferase (HAT) activity in the hippocampus. In addition, H3(K4)me3, which is closely associated with transcriptional initiation, was also augmented in the hippocampus three weeks after the last defeat. Inhibition of HAT by curcumin (100mg/kg) before each SD blocked the increase in the conditioned reinforcing effects of 1mg/kg of cocaine, while inhibition of HDAC by valproic acid (500mg/kg) before social stress potentiated cocaine-induced CPP. Preference was reinstated when animals received a priming dose of 0.5mg/kg of cocaine, an effect that was absent in untreated defeated mice. These results suggest that the experience of SD induces chromatin remodeling, alters histone acetylation and methylation, and modifies the effects of cocaine on place conditioning. They also point to epigenetic mechanisms as potential avenues leading to new treatments for the long-term effects of social stress on drug addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

PubMed

Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

2016-09-15

Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

PubMed

Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

2015-10-01

Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Involvement of the lateral septum and the ventral Hippocampus in the emotional sequelae induced by social defeat: role of glucocorticoid receptors.

PubMed

Calfa, Gastón; Bussolino, Daniela; Molina, Victor A

2007-07-19

An important area of the brain aversive circuitry is the lateral septum (LS), together with its principal connections to diverse Hippocampal regions. The aim of this work was to evaluate whether the LS-Hippocampus network participates in the increased anxiety-like behavior produced by a previous defeat experience. The neural activation of different regions of the Hippocampus was assessed by the number of Fos positive cells in animals previously defeated. A notable elevation in the expression of this protein was observed in CA1, CA2, CA3, and Dentate Gyrus, for both dorsal and ventral Hippocampus. The local administration of a glucocorticoid receptor (GR or type II) antagonist, but not of a mineralcorticoid receptor (MR or type II) antagonist, into the LS before the stressful stimuli prevented a rise in the number of Fos positive cells, especially in the ventral portion of the Hippocampus. Furthermore, to evaluate the role of these hippocampal portions in the modulation of the emotional sequelae induced by defeat, the dorsal or the ventral Hippocampus were inactivated by lidocaine at different times following the social confrontation, with the anxiety-like behavior being assessed in the elevated plus maze the next day. Only the inactivation of the ventral region attenuated the excessive anxiety exhibited by defeated animals. The infusion of lidocaine, 1h after the confrontation, did not affect this behavioral response. These data suggest a preferential participation of the LS and its connections to the ventral Hippocampus in the emotional sequelae induced by the social defeat. Moreover, the GR localized within the LS played an essential role in the modulation of this emotional state.

Gene Expression in Aminergic and Peptidergic Cells During Aggression and Defeat: Relevance to Violence, Depression and Drug Abuse

PubMed Central

Nikulina, Ella M.; Takahashi, Aki; Covington, Herbert E.; Yap, Jasmine J.; Boyson, Christopher O.; Shimamoto, Akiko; de Almeida, Rosa M. M.

2013-01-01

In this review, we examine how experiences in social confrontations alter gene expression in mesocorticolimbic cells. The focus is on the target of attack and threat due to the prominent role of social defeat stress in the study of coping mechanisms and victimization. The initial operational definition of the socially defeated mouse by Ginsburg and Allee (1942) enabled the characterization of key endocrine, cardiovascular, and metabolic events during the initial response to an aggressive opponent and during the ensuing adaptations. Brief episodes of social defeat stress induce an augmented response to stimulant challenge as reflected by increased locomotion and increased extracellular dopamine (DA) in the nucleus accumbens (NAC). Cells in the ventral tegmental area (VTA) that project to the NAC were more active as indicated by increased expression of c-fos and Fos-immunoreactivity and BDNF. Intermittent episodes of social defeat stress result in increased mRNA for MOR in brainstem and limbic structures. These behavioral and neurobiological indices of sensitization persist for several months after the stress experience. The episodically defeated rats also self-administered intravenous cocaine during continuous access for 24 h (“binge”). By contrast, continuous social stress, particularly in the form of social subordination stress, leads to reduced appetite, compromised endocrine activities, and cardiovascular and metabolic abnormalities, and prefer sweets less as index of anhedonia. Cocaine challenges in subordinate rats result in a blunted psychomotor stimulant response and a reduced DA release in NAC. Subordinate rats self-administer cocaine less during continuous access conditions. These contrasting patterns of social stress result from continuous vs. intermittent exposure to social stress, suggesting divergent neuroadaptations for increased vulnerability to cocaine self-administration vs. deteriorated reward mechanisms characteristic of depressive-like profiles. PMID:21416141

Overlapping neurobiology of learned helplessness and conditioned defeat: implications for PTSD and mood disorders.

PubMed

Hammack, Sayamwong E; Cooper, Matthew A; Lezak, Kimberly R

2012-02-01

Exposure to traumatic events can increase the risk for major depressive disorder (MDD) as well as posttraumatic stress disorder (PTSD), and pharmacological treatments for these disorders often involve the modulation of serotonergic (5-HT) systems. Several behavioral paradigms in rodents produce changes in behavior that resemble symptoms of MDD and these behavioral changes are sensitive to antidepressant treatments. Here we review two animal models in which MDD-like behavioral changes are elicited by exposure to an acute traumatic event during adulthood, learned helplessness (LH) and conditioned defeat. In LH, exposure of rats to inescapable, but not escapable, tailshock produces a constellation of behavioral changes that include deficits in fight/flight responding and enhanced anxiety-like behavior. In conditioned defeat, exposure of Syrian hamsters to a social defeat by a more aggressive animal leads to a loss of territorial aggression and an increase in submissive and defensive behaviors in subsequent encounters with non-aggressive conspecifics. Investigations into the neural substrates that control LH and conditioned defeat revealed that increased 5-HT activity in the dorsal raphe nucleus (DRN) is critical for both models. Other key brain regions that regulate the acquisition and/or expression of behavior in these two paradigms include the basolateral amygdala (BLA), central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST). In this review, we compare and contrast the role of each of these neural structures in mediating LH and conditioned defeat, and discuss the relevance of these data in developing a better understanding of the mechanisms underlying trauma-related depression. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of chronic social defeat stress on behaviour, endoplasmic reticulum proteins and choline acetyltransferase in adolescent mice.

PubMed

Huang, Guang-Biao; Zhao, Tong; Muna, Sushma Shrestha; Bagalkot, Tarique Rajasaheb; Jin, Hong-Mei; Chae, Han-Jung; Chung, Young-Chul

2013-08-01

The present study investigated the effects of social defeat stress on the behaviours and expressions of 78-kDa glucose-regulated protein (Grp78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and choline acetyltransferase (Chat) in the brains of adolescent mice. Adolescent male C57BL/6J mice were divided into two groups (susceptible and unsusceptible) after 10 d social defeat stress. In expt 1, behavioural tests were conducted and brains were processed for Western blotting on day 21 after stress. In expt 2, social avoidance tests were conducted and brains were subsequently processed for Western blotting on day 12 after stress. Chronic social defeat stress produced more pronounced depression-like behaviours such as decreased locomotion and social interaction, increased anxiety-like behaviours and immobility, and impaired memory performance in susceptible mice. Moreover, susceptible mice showed greater expression of Grp78 and CHOP in the amygdala (Amyg) on days 12 and 21 compared with the other groups. Susceptible and unsusceptible groups showed significant increases in Grp78 and CHOP expression in the prefrontal cortex (PFC) and hippocampus (Hipp) on day 12 compared with the control group; this persisted until day 21. The levels of Chat measured on days 12 and 21 were significantly lower in the PFC, Amyg and Hipp of all defeated mice compared with controls. The findings of the behavioural tests indicate that chronic social defeat in adolescents produces anxiety-like behaviours, social withdrawal, despair-like behaviours and cognitive impairment. The Grp78, CHOP and Chat results suggest that the selective response of endoplasmic reticulum stress proteins in the Amyg plays an important role in the vulnerability-stress model of depression.

Self-Defeating Behavior Workshops: Systems Approach for Hard-to-Serve Veterans.

ERIC Educational Resources Information Center

Banks, Jerry; And Others

1979-01-01

The self-defeating behavior (SDB) theory was applied to veterans who had problems in job training, vocational placement, and academic settings. A group-therapy structure meeting eight times during a four-week period was the basic approach of the SDB seminar. (Author)

Social defeat models in animal science: What we have learned from rodent models.

PubMed

Toyoda, Atsushi

2017-07-01

Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

From fan to fat? Vicarious losing increases unhealthy eating, but self-affirmation is an effective remedy.

PubMed

Cornil, Yann; Chandon, Pierre

2013-10-01

Using archival and experimental data, we showed that vicarious defeats experienced by fans when their favorite football team loses lead them to consume less healthy food. On the Mondays following a Sunday National Football League (NFL) game, saturated-fat and food-calorie intake increase significantly in cities with losing teams, decrease in cities with winning teams, and remain at their usual levels in comparable cities without an NFL team or with an NFL team that did not play. These effects are greater in cities with the most committed fans, when the opponents are more evenly matched, and when the defeats are narrow. We found similar results when measuring the actual or intended food consumption of French soccer fans who had previously been asked to write about or watch highlights from victories or defeats of soccer teams. However, these unhealthy consequences of vicarious defeats disappear when supporters spontaneously self-affirm or are given the opportunity to do so.

Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model

PubMed Central

Yang, Bangkun; Ren, Qian; Ma, Min; Chen, Qian-Xue

2016-01-01

Background: Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression. Methods: The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined. Results: In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer. Conclusions: Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days). PMID:27608811

Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model.

PubMed

Yang, Bangkun; Ren, Qian; Ma, Min; Chen, Qian-Xue; Hashimoto, Kenji

2016-12-01

Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression. The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined. In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer. Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days). © The Author 2016. Published by Oxford University Press on behalf of CINP.

Hamilton Standard Q-fan demonstrator dynamic pitch change test program, volume 1

NASA Technical Reports Server (NTRS)

Demers, W. J.; Nelson, D. J.; Wainauski, H. S.

1975-01-01

Tests of a full scale variable pitch fan engine to obtain data on the structural characteristics, response times, and fan/core engine compatibility during transient changes in blade angle, fan rpm, and engine power is reported. Steady state reverse thrust tests with a take off nozzle configuration were also conducted. The 1.4 meter diameter, 13 bladed controllable pitch fan was driven by a T55 L 11A engine with power and blade angle coordinated by a digital computer. The tests demonstrated an ability to change from full forward thrust to reverse thrust in less than one (1) second. Reverse thrust was effected through feather and through flat pitch; structural characteristics and engine/fan compatibility were within satisfactory limits.

The moderating effects of coping and self-esteem on the relationship between defeat, entrapment and suicidality in a sample of prisoners at high risk of suicide.

PubMed

Gooding, P; Tarrier, N; Dunn, G; Shaw, J; Awenat, Y; Ulph, F; Pratt, D

2015-11-01

Research is sparse which examines pathways to suicide, and resilience to suicide, in people who are particularly vulnerable to suicide, for example, prison inmates. The purpose of this study was to examine the ways in which perceptions of self-esteem and coping ability interacted with defeat and entrapment to both amplify suicidal thoughts and feelings, and to act as a buffer against suicidal thoughts and feelings. Participants were 65 male prisoners at high risk of suicide. A cross-sectional questionnaire design was used. Questionnaire measures of depression, defeat, entrapment, self-esteem, coping ability and suicidal probability were administered. For the hopelessness component of the suicide probability measure, high levels of coping ability together with low levels of defeat resulted in the lowest levels of suicidality indicative of a resilience factor. In contrast, low levels of coping skills together with high levels of entrapment were a high risk factor for this hopelessness component of suicide. This pattern of results pertained when controlling for depression levels. This is the first study to examine interactions between defeat, entrapment and appraisals of self-esteem and coping ability. Therapeutic interventions would benefit from boosting perceptions and appraisals of coping ability, in particular, in people who are at high risk for suicide. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The moderating effects of coping and self-esteem on the relationship between defeat, entrapment and suicidality in a sample of prisoners at high risk of suicide

PubMed Central

Gooding, P.; Tarrier, N.; Dunn, G.; Shaw, J.; Awenat, Y.; Ulph, F.; Pratt, D.

2015-01-01

Background Research is sparse which examines pathways to suicide, and resilience to suicide, in people who are particularly vulnerable to suicide, for example, prison inmates. The purpose of this study was to examine the ways in which perceptions of self-esteem and coping ability interacted with defeat and entrapment to both amplify suicidal thoughts and feelings, and to act as a buffer against suicidal thoughts and feelings. Methods Participants were 65 male prisoners at high risk of suicide. A cross-sectional questionnaire design was used. Questionnaire measures of depression, defeat, entrapment, self-esteem, coping ability and suicidal probability were administered. Results For the hopelessness component of the suicide probability measure, high levels of coping ability together with low levels of defeat resulted in the lowest levels of suicidality indicative of a resilience factor. In contrast, low levels of coping skills together with high levels of entrapment were a high risk factor for this hopelessness component of suicide. This pattern of results pertained when controlling for depression levels. Conclusions This is the first study to examine interactions between defeat, entrapment and appraisals of self-esteem and coping ability. Therapeutic interventions would benefit from boosting perceptions and appraisals of coping ability, in particular, in people who are at high risk for suicide. PMID:26497469

Strain-specific outcomes of repeated social defeat and chronic fluoxetine treatment in the mouse.

PubMed

Razzoli, Maria; Carboni, Lucia; Andreoli, Michela; Michielin, Francesca; Ballottari, Alice; Arban, Roberto

2011-01-01

Social stress is a risk factor for affective disorders in vulnerable individuals. Although the biological nature of stress susceptibility/resilience remains to be elucidated, genetic variation is considered amongst the principal contributors to brain disorders. Furthermore, genetic predisposition may be determinant for the therapeutic outcome, as proposed for antidepressant treatments. In the present studies we compared the inherently diverse genetic backgrounds of 2 mouse strains by assessing the efficacy of a chronic antidepressant treatment in a repeated social stress procedure. C57BL/6J and BalbC mice underwent 10-day social defeats followed by 28-day fluoxetine treatment (10 mg/kg/mL, p.o.). In C57BL/6J, most of the social defeat-induced changes were of metabolic nature including persistently altered feed efficiency and decreased abdominal fat stores that were ameliorated by fluoxetine. BalbC mouse behavior was persistently affected by social defeat both in the social avoidance and the forced swim tests, and in either procedure it was restored by chronic fluoxetine, whereas their endocrine parameters were mostly unaffected. The highlighted strain-specific responsivity to the metabolic and behavioral consequences of social defeat and to the chronic antidepressant treatment offers a promising research tool to further explore the underlying neural mechanisms and genetic basis of stress susceptibility and treatment response. Copyright © 2010 Elsevier Inc. All rights reserved.

Single aggressive and non-aggressive social interactions elicit distinct behavioral patterns to the context in mice.

PubMed

Crestani, Ariela M; Cipriano, Ana C; Nunes-de-Souza, Ricardo L

2018-04-16

Aggressive interactions between conspecific animals have been used as a social stressor with ethological characteristics to study how social interactions can modulate animal's behavior. Here, a new protocol based on aggressive and non-aggressive interactions was developed to study how different social interactions can alter the behavioral profile of animals re-exposed to the context in which the interaction occurred. We used factor analysis to trace the behavioral profile of socially defeated and non-defeated mice when they were re-exposed to the apparatus [three interconnected chambers: home chamber, tunnel and surface area]; we also compared the behavior presented before (habituation) and 24 h after (re-exposure) the non-aggressive or aggressive interactions. A final factor analysis from defeated animals yielded 4 factors that represented 72.09% of total variance; whereas non-defeated animal's analysis was loaded with 5 factors that represented 85.46% of total variance. A 5-min non-aggressive interaction reduced the frequency of stretched attend behavior in the tunnel, whereas a single social defeat reduced time in the tunnel and increased time spent performing self-grooming in the home chamber without conditioning any other spatio-temporal and complementary measures. Together, these results suggest that different social interactions may modulate distinct behavioral profiles in animals when re-exposed to the context. Copyright © 2018 Elsevier B.V. All rights reserved.

Reverse engineering and identification in systems biology: strategies, perspectives and challenges

PubMed Central

Villaverde, Alejandro F.; Banga, Julio R.

2014-01-01

The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology? PMID:24307566

Static Performance of a Wing-Mounted Thrust Reverser Concept

NASA Technical Reports Server (NTRS)

Asbury, Scott C.; Yetter, Jeffrey A.

1998-01-01

An experimental investigation was conducted in the Jet-Exit Test Facility at NASA Langley Research Center to study the static aerodynamic performance of a wing-mounted thrust reverser concept applicable to subsonic transport aircraft. This innovative engine powered thrust reverser system is designed to utilize wing-mounted flow deflectors to produce aircraft deceleration forces. Testing was conducted using a 7.9%-scale exhaust system model with a fan-to-core bypass ratio of approximately 9.0, a supercritical left-hand wing section attached via a pylon, and wing-mounted flow deflectors attached to the wing section. Geometric variations of key design parameters investigated for the wing-mounted thrust reverser concept included flow deflector angle and chord length, deflector edge fences, and the yaw mount angle of the deflector system (normal to the engine centerline or parallel to the wing trailing edge). All tests were conducted with no external flow and high pressure air was used to simulate core and fan engine exhaust flows. Test results indicate that the wing-mounted thrust reverser concept can achieve overall thrust reverser effectiveness levels competitive with (parallel mount), or better than (normal mount) a conventional cascade thrust reverser system. By removing the thrust reverser system from the nacelle, the wing-mounted concept offers the nacelle designer more options for improving nacelle aero dynamics and propulsion-airframe integration, simplifying nacelle structural designs, reducing nacelle weight, and improving engine maintenance access.

Defeat and entrapment as predictors of depression and suicidal ideation versus hopelessness and helplessness.

PubMed

Lester, David

2012-10-01

In a sample of 140 undergraduate students, measures of defeat and entrapment and of haplessness, helplessness, and hopelessness were similar in their ability to predict depression and suicidality. It was concluded that the two sets of measures may tap the same cognitive mind set.

Reverse Flow Engine Core Having a Ducted Fan with Integrated Secondary Flow Blades

NASA Technical Reports Server (NTRS)

Kisska, Michael K. (Inventor); Princen, Norman H. (Inventor); Kuehn, Mark S. (Inventor); Cosentino, Gary B. (Inventor)

2014-01-01

Secondary air flow is provided for a ducted fan having a reverse flow turbine engine core driving a fan blisk. The fan blisk incorporates a set of thrust fan blades extending from an outer hub and a set of integral secondary flow blades extending intermediate an inner hub and the outer hub. A nacelle provides an outer flow duct for the thrust fan blades and a secondary flow duct carries flow from the integral secondary flow blades as cooling air for components of the reverse flow turbine engine.

Application of reverse engineering in the medical industry.

NASA Astrophysics Data System (ADS)

Kaleev, A. A.; Kashapov, L. N.; Kashapov, N. F.; Kashapov, R. N.

2017-09-01

The purpose of this research is to develop on the basis of existing analogs new design of ophthalmologic microsurgical tweezers by using reverse engineering techniques. Virtual model was obtained by using a three-dimensional scanning system Solutionix Rexcan 450 MP. Geomagic Studio program was used to remove defects and inaccuracies of the obtained parametric model. A prototype of the finished model was made on the installation of laser stereolithography Projet 6000. Total time of the creation was 16 hours from the reverse engineering procedure to 3D-printing of the prototype.

GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

NASA Technical Reports Server (NTRS)

Cross, James H., II

1990-01-01

The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

Improved Short-Circuit Protection for Power Cells in Series

NASA Technical Reports Server (NTRS)

Davies, Francis

2008-01-01

A scheme for protection against short circuits has been devised for series strings of lithium electrochemical cells that contain built-in short-circuit protection devices, which go into a high-resistance, current-limiting state when heated by excessive current. If cells are simply connected in a long series string to obtain a high voltage and a short circuit occurs, whichever short-circuit protection device trips first is exposed to nearly the full string voltage, which, typically, is large enough to damage the device. Depending on the specific cell design, the damage can defeat the protective function, cause a dangerous internal short circuit in the affected cell, and/or cascade to other cells. In the present scheme, reverse diodes rated at a suitably high current are connected across short series sub-strings, the lengths of which are chosen so that when a short-circuit protection device is tripped, the voltage across it does not exceed its rated voltage. This scheme preserves the resetting properties of the protective devices. It provides for bypassing of cells that fail open and limits cell reversal, though not as well as does the more-expensive scheme of connecting a diode across every cell.

Prospective Predictors of Suicidality: Defeat and Entrapment Lead to Changes in Suicidal Ideation over Time

ERIC Educational Resources Information Center

Taylor, Peter James; Gooding, Patricia A.; Wood, Alex M.; Johnson, Judith; Tarrier, Nicholas

2011-01-01

Theoretical perspectives into suicidality have suggested that heightened perceptions of defeat and entrapment lead to suicidality. However, all previous empirical work has been cross-sectional. We provide the first longitudinal test of the theoretical predictions, in a sample of 79 students who reported suicidality. Participants completed…

The Myth of the Silver Bullet: Does Technical Superiority Equate to Battlefield Success?

DTIC Science & Technology

2012-03-30

Victorian period alone, the British army suffered significant defeats in India and Zululand and strategic defeat in Afghanistan, Sudan, and the Transvaal.28...capability of their systems and fought the battle in a fashion that maximized their weapons potential. It was, “Through the evolution of technological

Group Workshops to Eliminate Self-Defeating Behavior as an Alternative to Suspension in the Secondary School

ERIC Educational Resources Information Center

Burress, Carl B.

1978-01-01

Describes group workshops to eliminate self-defeating behavior as an alternative to suspension in the secondary school. Students who worked at understanding the SDB process reported they had better communication with their teachers and received fewer and in many cases no more disciplinary referrals. (Author)

Eliminating Self-Defeating Behaviors System.

ERIC Educational Resources Information Center

Cerio, James E.; And Others

This book takes a cognitive-behavioral approach to help readers learn a strategy for eliminating their self-defeating behaviors. It allows readers to move logically through a complete system for eliminating such behaviors. Unit 1 presents an introduction to the book and explains how to use it. It is recommended that readers read the text and…

Studies in Public Library Government, Organization, and Support. Final Report.

ERIC Educational Resources Information Center

Garrison, Guy

This report consists of six individual reports that were done by staff members at the Library Research Center as part of the overall project. In Part I, "Financing Public Library Expansion: Case Studies of Three Defeated Bond Issue Referendums," Ruth G. Lindahl and William S. Berner analyze defeated library bond issue referendums in…

20 CFR 408.913 - When would overpayment recovery defeat the purpose of the title VIII program?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false When would overpayment recovery defeat the purpose of the title VIII program? 408.913 Section 408.913 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Underpayments and Overpayments Waiver of...

20 CFR 408.913 - When would overpayment recovery defeat the purpose of the title VIII program?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false When would overpayment recovery defeat the purpose of the title VIII program? 408.913 Section 408.913 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Underpayments and Overpayments Waiver of...

20 CFR 408.913 - When would overpayment recovery defeat the purpose of the title VIII program?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false When would overpayment recovery defeat the purpose of the title VIII program? 408.913 Section 408.913 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Underpayments and Overpayments Waiver of...

Reverse and forward engineering of protein pattern formation.

PubMed

Kretschmer, Simon; Harrington, Leon; Schwille, Petra

2018-05-26

Living systems employ protein pattern formation to regulate important life processes in space and time. Although pattern-forming protein networks have been identified in various prokaryotes and eukaryotes, their systematic experimental characterization is challenging owing to the complex environment of living cells. In turn, cell-free systems are ideally suited for this goal, as they offer defined molecular environments that can be precisely controlled and manipulated. Towards revealing the molecular basis of protein pattern formation, we outline two complementary approaches: the biochemical reverse engineering of reconstituted networks and the de novo design, or forward engineering, of artificial self-organizing systems. We first illustrate the reverse engineering approach by the example of the Escherichia coli Min system, a model system for protein self-organization based on the reversible and energy-dependent interaction of the ATPase MinD and its activating protein MinE with a lipid membrane. By reconstituting MinE mutants impaired in ATPase stimulation, we demonstrate how large-scale Min protein patterns are modulated by MinE activity and concentration. We then provide a perspective on the de novo design of self-organizing protein networks. Tightly integrated reverse and forward engineering approaches will be key to understanding and engineering the intriguing phenomenon of protein pattern formation.This article is part of the theme issue 'Self-organization in cell biology'. © 2018 The Author(s).

Dysfunction of serotoninergic and dopaminergic neuronal systems in the antidepressant-resistant impairment of social behaviors induced by social defeat stress exposure as juveniles.

PubMed

Hasegawa, Sho; Miyake, Yuriko; Yoshimi, Akira; Mouri, Akihiro; Hida, Hirotake; Yamada, Kiyofumi; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2018-03-29

Extensive studies have been performed on the role of monoaminergic neuronal systems in rodents exposed to social defeat stress as adults. In the present study, we investigated the role of monoaminergic neuronal systems in the impairment of social behaviors induced by social defeat stress exposure as juveniles. Juvenile, male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days. From 1 day after the last stress exposure, desipramine, sertraline, and aripiprazole, were administered for 15 days. Social behaviors were assessed at 1 and 15 days after the last stress exposure. Monoamine turnover was determined in specific regions of the brain in the mice exposed to the stress. Stress exposure as juveniles induced the impairment of social behaviors in adolescent mice. In mice that showed the impairment of social behaviors, turnover of the serotonin and dopamine, but not noradrenaline was decreased in specific brain regions. Acute and repeated administration of desipramine, sertraline, and aripiprazole failed to attenuate the impairment of social behaviors, whereas repeated administration of a combination of sertraline and aripiprazole showed additive attenuating effects. These findings suggest that social defeat stress exposure as juveniles induces the treatment-resistant impairment of social behaviors in adolescents through dysfunction in the serotoninergic and dopaminergic neuronal systems. The combination of sertraline and aripiprazole may be used as a new treatment strategy for treatment-resistant stress-related psychiatric disorders in adolescents with adverse juvenile experiences.

Dynamics of high-bypass-engine thrust reversal using a variable-pitch fan

NASA Technical Reports Server (NTRS)

Schaefer, J. W.; Sagerser, D. R.; Stakolich, E. G.

1977-01-01

The test program demonstrated that successful and rapid forward-to reverse-thrust transients can be performed without any significant engine operational limitations for fan blade pitch changes through either feather pitch or flat pitch. For through-feather-pitch operation with a flight inlet, fan stall problems were encountered, and a fan blade overshoot technique was used to establish reverse thrust.

Early life experience alters behavior during social defeat: focus on serotonergic systems.

PubMed

Gardner, K L; Thrivikraman, K V; Lightman, S L; Plotsky, P M; Lowry, C A

2005-01-01

Early life experience can have prolonged effects on neuroendocrine, autonomic, and behavioral responses to stress. The objective of this study was to investigate the effects of early life experience on behavior during social defeat, as well as on associated functional cellular responses in serotonergic and non-serotonergic neurons within the dorsal raphe nucleus, a structure which plays an important role in modulation of stress-related physiology and behavior. Male Long Evans rat pups were exposed to either normal animal facility rearing or 15 min or 180 min of maternal separation from postnatal days 2-14. As adults, these rats were exposed to a social defeat protocol. Differences in behavior were seen among the early life treatment groups during social defeat; rats exposed to 180 min of maternal separation from postnatal days 2-14 displayed more passive-submissive behaviors and less proactive coping behaviors. Analysis of the distribution of tryptophan hydroxylase and c-Fos-like immunoreactivity in control rats exposed to a novel cage and rats exposed to social defeat revealed that, independent of the early life experience, rats exposed to social defeat showed an increase in the number of c-Fos-like immunoreactive nuclei in serotonergic neurons in the middle and caudal parts of the dorsal dorsal raphe nucleus and caudal part of the ventral dorsal raphe nucleus, regions known to contain serotonergic neurons projecting to central autonomic and emotional motor control systems. This is the first study to show that the dorsomedial part of the mid-rostrocaudal dorsal raphe nucleus is engaged by a naturalistic stressor and supports the hypothesis that early life experience alters behavioral coping strategies during social conflict; furthermore, this study is consistent with the hypothesis that topographically organized subpopulations of serotonergic neurons principally within the mid-rostrocaudal and caudal part of the dorsal dorsal raphe nucleus modulate stress-related physiological and behavioral responses.

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

PubMed

Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

2015-08-27

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain

PubMed Central

Sawicki, Caroline M.; McKim, Daniel B.; Wohleb, Eric S.; Jarrett, Brant L.; Reader, Brenda F.; Norden, Diana M.; Godbout, Jonathan P.; Sheridan, John F.

2014-01-01

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain-myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b+ cells (microglia/macrophages) and enriched GLAST-1+/CD11b− cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain-region dependent manner. PMID:25445193

A gene network simulator to assess reverse engineering algorithms.

PubMed

Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

2009-03-01

In the context of reverse engineering of biological networks, simulators are helpful to test and compare the accuracy of different reverse-engineering approaches in a variety of experimental conditions. A novel gene-network simulator is presented that resembles some of the main features of transcriptional regulatory networks related to topology, interaction among regulators of transcription, and expression dynamics. The simulator generates network topology according to the current knowledge of biological network organization, including scale-free distribution of the connectivity and clustering coefficient independent of the number of nodes in the network. It uses fuzzy logic to represent interactions among the regulators of each gene, integrated with differential equations to generate continuous data, comparable to real data for variety and dynamic complexity. Finally, the simulator accounts for saturation in the response to regulation and transcription activation thresholds and shows robustness to perturbations. It therefore provides a reliable and versatile test bed for reverse engineering algorithms applied to microarray data. Since the simulator describes regulatory interactions and expression dynamics as two distinct, although interconnected aspects of regulation, it can also be used to test reverse engineering approaches that use both microarray and protein-protein interaction data in the process of learning. A first software release is available at http://www.dei.unipd.it/~dicamill/software/netsim as an R programming language package.

Reverse engineering biomolecular systems using -omic data: challenges, progress and opportunities.

PubMed

Quo, Chang F; Kaddi, Chanchala; Phan, John H; Zollanvari, Amin; Xu, Mingqing; Wang, May D; Alterovitz, Gil

2012-07-01

Recent advances in high-throughput biotechnologies have led to the rapid growing research interest in reverse engineering of biomolecular systems (REBMS). 'Data-driven' approaches, i.e. data mining, can be used to extract patterns from large volumes of biochemical data at molecular-level resolution while 'design-driven' approaches, i.e. systems modeling, can be used to simulate emergent system properties. Consequently, both data- and design-driven approaches applied to -omic data may lead to novel insights in reverse engineering biological systems that could not be expected before using low-throughput platforms. However, there exist several challenges in this fast growing field of reverse engineering biomolecular systems: (i) to integrate heterogeneous biochemical data for data mining, (ii) to combine top-down and bottom-up approaches for systems modeling and (iii) to validate system models experimentally. In addition to reviewing progress made by the community and opportunities encountered in addressing these challenges, we explore the emerging field of synthetic biology, which is an exciting approach to validate and analyze theoretical system models directly through experimental synthesis, i.e. analysis-by-synthesis. The ultimate goal is to address the present and future challenges in reverse engineering biomolecular systems (REBMS) using integrated workflow of data mining, systems modeling and synthetic biology.

7 CFR 760.622 - Incorrect or false producer production evidence.

Code of Federal Regulations, 2010 CFR

2010-01-01

... production evidence acted in good faith or took action to defeat the purposes of the program, such that the... participant who submitted the evidence did not act in good faith or took action to defeat the purposes of the... evidence acted in good faith, payment may be adjusted and a refund may be required. ...

The Association between Self-Defeating Personality Characteristics, Career Indecision, and Vocational Identity.

ERIC Educational Resources Information Center

Sweeney, Marie L.; Schill, Thomas R.

1998-01-01

Of 81 men and 69 women studied, those with more self-defeating personality (SDP) characteristics were more career indecisive and had less vocational identity. Women with more SDP had significantly greater career choice anxiety than similar men. Depression contributed to indecision and lack of vocational identity for SDP men and to lack of…

France Says "Non": Elites, Masses and the Defeat of the European Constitutional Treaty

ERIC Educational Resources Information Center

Nossiter, Jason

2008-01-01

On Sunday, May 29, 2005, the French Republic endured one of the greatest political shocks in its recent history. By a wide margin, the TCE (Treaty establishing a Constitution for Europe) was defeated in a referendum, effectively paralyzing the process of European political integration while simultaneously crippling both the ruling Union Pour le…

The Efforts of Educational Interest Groups To Defeat Merit Pay for Teachers in Pennsylvania: 1983-1986.

ERIC Educational Resources Information Center

Fiore, Alice Marie

Efforts of educational interest groups to defeat merit pay for Pennsylvania teachers during 1983-1986 are explored in this case study. Political systems theory and allocative theory provide the conceptual framework. Deutsch's (1973) outline of variables that affect the course of conflict was used to organize indepth personal interviews and a…

Role of Amygdala and Hippocampus in the Neural Circuit Subserving Conditioned Defeat in Syrian Hamsters

ERIC Educational Resources Information Center

Markham, Chris M.; Taylor, Stacie L.; Huhman, Kim L.

2010-01-01

We examined the roles of the amygdala and hippocampus in the formation of emotionally relevant memories using an ethological model of conditioned fear termed conditioned defeat (CD). Temporary inactivation of the ventral, but not dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the acquisition of CD, whereas pretraining VH…

Disrupting Improvised Explosive Device Terror Campaigns: Basic Research Opportunities

DTIC Science & Technology

2008-01-01

2008 2. REPORT TYPE 3. DATES COVERED 00-00-2008 to 00-00-2008 4. TITLE AND SUBTITLE Disrupting Improvised Explosive Device Terror Campaigns... Explosive Device Terror Campaigns: Basic Research Opportunities A WORKSHOP REPORT Committee on Defeating Improvised Explosive Devices...iv v COMMITTEE ON DEFEATING IMPROVISED EXPLOSIVE DEVICES: BASIC RESEARCH TO INTERRUPT THE IED DELIVERY CHAIN Chairperson

28. MESTA STEAM ENGINE, INSTALLED BY THE CORRIGAN, McKINNEY COMPANY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. MESTA STEAM ENGINE, INSTALLED BY THE CORRIGAN, McKINNEY COMPANY IN 1916, STILL DRIVES THE 44-INCH REVERSING BLOOMING MILL. THE TWIN TANDAM, COMPOUND CONDENSING, REVERSING STEAM ENGINE HAS A RATED CAPACITY OF 35,000 H.P. IT WAS BUILT BY THE MESTA MACHINE COMPANY OF PITTSBURGH. - Corrigan, McKinney Steel Company, 3100 East Forty-fifth Street, Cleveland, Cuyahoga County, OH

Analysis and documentation of QCSEE (Quiet Clean Short-haul Experimental Engine) over-the-wing exhaust system development

NASA Technical Reports Server (NTRS)

Ammer, R. C.; Kutney, J. T.

1977-01-01

A static scale model test program was conducted in the static test area of the NASA-Langley 9.14- by 18.29 m(30- by 60-ft) Full-Scale Wind Tunnel Facility to develop an over-the-wing (OTW) nozzle and reverser configuration for the Quiet Clean Short-Haul Experimental Engine (QCSEE). Three nozzles and one basic reverser configuration were tested over the QCSEE takeoff and approach power nozzle pressure ratio range between 1.1 and 1.3. The models were scaled to 8.53% of QCSEE engine size and tested behind two 13.97-cm (5.5-in.) diameter tip-turbine-driven fan simulators coupled in tandem. An OTW nozzle and reverser configuration was identified which satisfies the QCSEE experimental engine requirements in terms of nozzle cycle area variation capability and reverse thrust level, and provides good jet flow spreading over a wing upper surface for achievement of high propulsive lift performance.

Vicarious social defeat stress: Bridging the gap between physical and emotional stress.

PubMed

Sial, Omar K; Warren, Brandon L; Alcantara, Lyonna F; Parise, Eric M; Bolaños-Guzmán, Carlos A

2016-01-30

Animal models capable of differentiating the neurobiological intricacies between physical and emotional stress are scarce. Current models rely primarily on physical stressors (e.g., chronic unpredictable or mild stress, social defeat, learned helplessness), and neglect the impact of psychological stress alone. This is surprising given extensive evidence that a traumatic event needs not be directly experienced to produce enduring perturbations on an individual's health and psychological well-being. Post-traumatic stress disorder (PTSD), a highly debilitating neuropsychiatric disorder characterized by intense fear of trauma-related stimuli, often occurs in individuals that have only witnessed a traumatic event. By modifying the chronic social defeat stress (CSDS) paradigm to include a witness component (witnessing the social defeat of another mouse), we demonstrate a novel behavioral paradigm capable of inducing a robust behavioral syndrome reminiscent of PTSD in emotionally stressed adult mice. We describe the vicarious social defeat stress (VSDS) model that is capable of inducing a host of behavioral deficits that include social avoidance and other depressive- and anxiety-like phenotypes in adult male mice. VSDS exposure induces weight loss and spike in serum corticosterone (CORT) levels. A month after stress, these mice retain the social avoidant phenotype and have an increased CORT response when exposed to subsequent stress. The VSDS is a novel paradigm capable of inducing emotional stress by isolating physical stress/confrontation in mice. The VSDS model can be used to study the short- and long-term neurobiological consequences of exposure to emotional stress in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Juvenile social defeat stress exposure persistently impairs social behaviors and neurogenesis.

PubMed

Mouri, Akihiro; Ukai, Mayu; Uchida, Mizuki; Hasegawa, Sho; Taniguchi, Masayuki; Ito, Takahiro; Hida, Hirotake; Yoshimi, Akira; Yamada, Kiyofumi; Kunimoto, Shohko; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2018-05-01

Adverse juvenile experiences, including physical abuse, often have negative health consequences later in life. We investigated the influence of social defeat stress exposure as juveniles on neuropsychological behaviors, and the causal role of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR mouse. Social defeat stress exposure as juveniles, even for 1 day, induced persistent social avoidance to the unfamiliar ICR mouse in the social interaction test, but that was not observed in mice exposed to the stress as adults. Social avoidance by the stress exposure as juveniles for 10 consecutive days was observed, when the target mouse was not only unfamiliar ICR but also another C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress exposure did not induce anxiety- and depression-like behaviors in spontaneous locomotor activity, elevated plus-maze test, marble-burying test, forced swimming test, or sucrose preference test. Serum corticosterone levels increased immediately after the stress exposure. The hippocampal neurogenesis was suppressed 1 day and 4 weeks after the stress exposure. Administration of mifepristone, a glucocorticoid receptor antagonist, prior to each stress exposure, blocked the persistent social avoidance and suppression of neurogenesis. In conclusion, social avoidance induced by social defeat stress exposure as juveniles are more persistent than that as adults. These social avoidances are associated with suppression of hippocampal neurogenesis via glucocorticoid receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantum engine efficiency bound beyond the second law of thermodynamics.

PubMed

Niedenzu, Wolfgang; Mukherjee, Victor; Ghosh, Arnab; Kofman, Abraham G; Kurizki, Gershon

2018-01-11

According to the second law, the efficiency of cyclic heat engines is limited by the Carnot bound that is attained by engines that operate between two thermal baths under the reversibility condition whereby the total entropy does not increase. Quantum engines operating between a thermal and a squeezed-thermal bath have been shown to surpass this bound. Yet, their maximum efficiency cannot be determined by the reversibility condition, which may yield an unachievable efficiency bound above unity. Here we identify the fraction of the exchanged energy between a quantum system and a bath that necessarily causes an entropy change and derive an inequality for this change. This inequality reveals an efficiency bound for quantum engines energised by a non-thermal bath. This bound does not imply reversibility, unless the two baths are thermal. It cannot be solely deduced from the laws of thermodynamics.

A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy.

PubMed

Zhang, Erhao; Xu, Hanmei

2017-01-03

Adoptive cell therapy using chimeric antigen receptor (CAR)-engineered T cells has emerged as a very promising approach to combating cancer. Despite its ability to eliminate tumors shown in some clinical trials, CAR-T cell therapy involves some significant safety challenges, such as cytokine release syndrome (CRS) and "on-target, off-tumor" toxicity, which is related to poor control of the dose, location, and timing of T cell activity. In the past few years, some strategies to avoid the side effects of CAR-T cell therapy have been reported, including suicide gene, inhibitory CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions. Because of the advances of the CAR paradigm and other forms of cancer immunotherapy, the most effective means of defeating the cancer has become the integration therapy with the combinatorial control system of switchable dual-receptor CAR-T cell and immune checkpoint blockade.

Numerical Prediction of the Influence of Thrust Reverser on Aeroengine's Aerodynamic Stability

NASA Astrophysics Data System (ADS)

Zhiqiang, Wang; Xigang, Shen; Jun, Hu; Xiang, Gao; Liping, Liu

2017-11-01

A numerical method was developed to predict the aerodynamic stability of a high bypass ratio turbofan engine, at the landing stage of a large transport aircraft, when the thrust reverser was deployed. 3D CFD simulation and 2D aeroengine aerodynamic stability analysis code were performed in this work, the former is to achieve distortion coefficient for the analysis of engine stability. The 3D CFD simulation was divided into two steps, the single engine calculation and the integrated aircraft and engine calculation. Results of the CFD simulation show that with the decreasing of relative wind Mach number, the engine inlet will suffer more severe flow distortion. The total pressure and total temperature distortion coefficients at the inlet of the engines were obtained from the results of the numerical simulation. Then an aeroengine aerodynamic stability analysis program was used to quantitatively analyze the aerodynamic stability of the high bypass ratio turbofan engine. The results of the stability analysis show that the engine can work stably, when the reverser flow is re-ingested. But the anti-distortion ability of the booster is weaker than that of the fan and high pressure compressor. It is a weak link of engine stability.

Wind tunnel test of model target thrust reversers for the Pratt and Whitney aircraft JT8D-100 series engines installed on a 727-200 airplane

NASA Technical Reports Server (NTRS)

Hambly, D.

1974-01-01

The results of a low speed wind tunnel test of 0.046 scale model target thrust reversers installed on a 727-200 model airplane are presented. The full airplane model was mounted on a force balance, except for the nacelles and thrust reversers, which were independently mounted and isolated from it. The installation had the capability of simulating the inlet airflows and of supplying the correct proportions of primary and secondary air to the nozzles. The objectives of the test were to assess the compatibility of the thrust reversers target door design with the engine and airplane. The following measurements were made: hot gas ingestion at the nacelle inlets; model lift, drag, and pitching moment; hot gas impingement on the airplane structure; and qualitative assessment of the rudder effectiveness. The major parameters controlling hot gas ingestion were found to be thrust reverser orientation, engine power setting, and the lip height of the bottom thrust reverser doors on the side nacelles. The thrust reversers tended to increase the model lift, decrease the drag, and decrease the pitching moment.

Operational Shock Complexity Theory

DTIC Science & Technology

2005-05-26

Theory : Recommendations For The National Strategy To Defeat Terrorism.” Student Issue Paper, Center for Strategic Leadership , US Army War College, July...Lens of Complexity Theory : Recommendations For The National Strategy To Defeat Terrorism.” (Student Issue Paper, Center for Strategic Leadership , US... Leadership Complexity theory affects the training of leaders. With the enemy system able to develop its complexity either through interaction with US

20 CFR 30.516 - Under what circumstances would recovery of an overpayment defeat the purpose of the Act?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Under what circumstances would recovery of an overpayment defeat the purpose of the Act? 30.516 Section 30.516 Employees' Benefits OFFICE OF WORKERS...' expenditures as determined by OWCP using the Bureau of Labor Statistics Consumer Expenditure Survey tables. ...

Reverse engineering systems models of regulation: discovery, prediction and mechanisms.

PubMed

Ashworth, Justin; Wurtmann, Elisabeth J; Baliga, Nitin S

2012-08-01

Biological systems can now be understood in comprehensive and quantitative detail using systems biology approaches. Putative genome-scale models can be built rapidly based upon biological inventories and strategic system-wide molecular measurements. Current models combine statistical associations, causative abstractions, and known molecular mechanisms to explain and predict quantitative and complex phenotypes. This top-down 'reverse engineering' approach generates useful organism-scale models despite noise and incompleteness in data and knowledge. Here we review and discuss the reverse engineering of biological systems using top-down data-driven approaches, in order to improve discovery, hypothesis generation, and the inference of biological properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Self-defeating behaviors in organizations: the relationship between thwarted belonging and interpersonal work behaviors.

PubMed

Thau, Stefan; Aquino, Karl; Poortvliet, P Marijn

2007-05-01

This multisource field study applied belongingness theory to examine whether thwarted belonging, defined as the perceived discrepancy between one's desired and actual levels of belonging with respect to one's coworkers, predicts interpersonal work behaviors that are self-defeating. Controlling for demographic variables, job type, justice constructs, and trust in organization in a multilevel regression analysis using data from 130 employees of a clinical chemical laboratory and their supervisors, the authors found that employees who perceive greater levels of desired coworker belonging than actual levels of coworker belonging were more likely to engage in interpersonally harmful and less likely to engage in interpersonally helpful behaviors. Implications for the application of belongingness theory to explain self-defeating behaviors in organizations are discussed. 2007 APA, all rights reserved

Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.

PubMed

Peña, Catherine J; Kronman, Hope G; Walker, Deena M; Cates, Hannah M; Bagot, Rosemary C; Purushothaman, Immanuel; Issler, Orna; Loh, Yong-Hwee Eddie; Leong, Tin; Kiraly, Drew D; Goodman, Emma; Neve, Rachael L; Shen, Li; Nestler, Eric J

2017-06-16

Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 ( Otx2 ) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. This work establishes a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2 . Copyright © 2017, American Association for the Advancement of Science.

Disaster Averted, For Now: How the American Health Care Act Would Have Affected Californians.

PubMed

Rasmussen, Petra W

2017-03-01

Although the American Health Care Act (AHCA) was recently defeated, the policies in the bill represented a mix of ideas long favored by conservatives. If enacted, this repeal-and-replace bill would have had devastating consequences for most of the 5 million Californians currently receiving direct benefits from the Affordable Care Act (ACA), including more than 1 million who receive subsidies through Covered California and almost 4 million who have enrolled in the Medi-Cal expansion. Although the bill failed to garner enough votes for passage, it is likely that efforts to chip away at the ACA will continue and that some of the ideas contained within the AHCA will be revisited. This policy brief summarizes some of the most significant reversals that would have occurred under the Republican plan in the individual and small group insurance markets.

Inventing the Invented for STEM Understanding

ERIC Educational Resources Information Center

Stansell, Alicia; Tyler-Wood, Tandra; Stansell, Christina

2016-01-01

The reverse engineering of simple inventions that were of historic significance is now possible in a classroom by using digital models provided by places like the Smithsonian. The digital models can facilitate the mastery of students' STEM learning by utilizing digital fabrication in maker spaces to provide an opportunity for reverse engineer and…

The design of a long-range megatransport aircraft

NASA Technical Reports Server (NTRS)

Weisshaar, Terrence A.; Allen, Carl L.

1992-01-01

Aircraft manufacturers are examining the market and feasibility of long-range passenger aircraft carrying more than 600 passengers. These aircraft would carry travelers at reduced cost and, at the same time, reduce congestion around major airports. The design of a large, long-range transport involves broad issues such as: the integration of airport terminal facilities; passenger loading and unloading; trade-offs between aircraft size and the cost to reconfigure these existing facilities; and, defeating the 'square-cube' law. Thirteen Purdue design teams generated RFP's that defined passenger capability and range, based upon team perception of market needs and infrastructure constraints. Turbofan engines were designed by each group to power these aircraft. The design problem and the variety of solutions developed are reviewed.

Can the United States Defeat Al Qaeda?

DTIC Science & Technology

2010-03-01

designed his organization to be so diverse as to be virtually indestructible. His efforts have led to an extensively franchised network of terror...and durability, makes them nearly impossible to defeat in the classical context. In addition, the franchised nature of its affiliation with other...specific geographic locale, it more clearly resembles a franchise based on affiliations with other violent extremist organizations.43 This widely

Defeating the Modern Asymmetric Threat

DTIC Science & Technology

2002-06-01

Rational Peasant. Berkeley, CA: University of California Press. Post, J. (1986). “ Narcissism and the Charismatic Leader-Follower Relationship ...to defeat the LTTE, which is what occurred until 7 shortly after the events of September 11th, 2001 in the U.S. which had global impacts that... social systems. Differences in ethnicity, religion, language, and social class created internal pressures on the island. The geo-strategic importance

Defeating Violent Nonstate Actors

DTIC Science & Technology

2013-01-01

Chiefs of Staff, December 19, 2012), 38, 39. 4 Ibid. 5 Odierno, Amos, and McRaven, Strategic Landpower, 3. Fighting irregulAr Fighters Defeating...or Ringing Hollow?” Army, August 2013, 18-20. Fighting irregular Fighters Bunker 59 and corruption capability. Organized into private armies...the state. Via one process, the synergistic employment of violence and corruption, plato o plomo (silver or lead in Spanish), results in areas of

Synthesis, Characterization, and Multimillion-Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat

DTIC Science & Technology

2013-04-01

DTRA-TR-13-23 Synthesis, Characterization, and Multimillion -Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat Approved for...reagents for the destruction of biologically active materials and a simulation of their reactions on a multimillion atom scale with quantum...explosives for destruction of chemical & biological agents. Multimillion -atom molecular dynamics simulations with quantum mechanical accuracy were

A fighter's comeback: dopamine is necessary for recovery of aggression after social defeat in crickets.

PubMed

Rillich, Jan; Stevenson, Paul A

2014-09-01

Social defeat, i.e. losing an agonistic dispute with a conspecific, is followed by a period of suppressed aggressiveness in many animal species, and is generally regarded as a major stressor, which may play a role in psychiatric disorders such as depression and post-traumatic stress disorder. Despite numerous animal models, the mechanisms underlying loser depression and subsequent recovery are largely unknown. This study on crickets is the first to show that a neuromodulator, dopamine (DA), is necessary for recovery of aggression after social defeat. Crickets avoid any conspecific male just after defeat, but regain their aggressiveness over 3 h. This recovery was prohibited after depleting nervous stores of DA and octopamine (OA, the invertebrate analogue of noradrenaline) with α-methyl-tyrosine (AMT). Loser recovery was also prohibited by the insect DA-receptor (DAR) antagonist fluphenazine, but not the OA-receptor (OAR) blocker epinastine, or yohimbine, which blocks receptors for OA's precursor tyramine. Conversely, aggression was restored prematurely in both untreated and amine depleted losers given either chlordimeform (CDM), a tissue permeable OAR-agonist, or the DA-metabolite homovanillyl alcohol (HVA), a component of the honeybee queen mandibular pheromone. As in honeybees, HVA acts in crickets as a DAR-agonist since its aggression promoting effect on losers was selectively blocked by the DAR-antagonist, but not by the OAR-antagonist. Conversely, CDM's aggression promoting effect was selectively blocked by the OAR-antagonist, but not the DAR-antagonist. Hence, only DA is necessary for recovery of aggressiveness after social defeat, although OA can promote loser aggression independently to enable experience dependent adaptive responses. Copyright © 2014 Elsevier Inc. All rights reserved.

Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress.

PubMed

Francis, T Chase; Chandra, Ramesh; Friend, Danielle M; Finkel, Eric; Dayrit, Genesis; Miranda, Jorge; Brooks, Julie M; Iñiguez, Sergio D; O'Donnell, Patricio; Kravitz, Alexxai; Lobo, Mary Kay

2015-02-01

The nucleus accumbens is a critical mediator of depression-related outcomes to social defeat stress. Previous studies demonstrate distinct neuroplasticity adaptations in the two medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 versus dopamine receptor D2, in reward and reinforcement leading to opposing roles for these MSNs in these behaviors. However, the distinct roles of nucleus accumbens MSN subtypes, in depression, remain poorly understood. Using whole-cell patch clamp electrophysiology, we examined excitatory input to MSN subtypes and intrinsic excitability measures in D1-green fluorescent protein and D2-green fluorescent protein bacterial artificial chromosome transgenic mice that underwent chronic social defeat stress (CSDS). Optogenetic and pharmacogenetic approaches were used to bidirectionally alter firing of D1-MSNs or D2-MSNs after CSDS or before a subthreshold social defeat stress in D1-Cre or D2-Cre bacterial artificial chromosome transgenic mice. We demonstrate that the frequency of excitatory synaptic input is decreased in D1-MSNs and increased in D2-MSNs in mice displaying depression-like behaviors after CSDS. Enhancing activity in D1-MSNs results in resilient behavioral outcomes, while inhibition of these MSNs induces depression-like outcomes after CSDS. Bidirectional modulation of D2-MSNs does not alter behavioral responses to CSDS; however, repeated activation of D2-MSNs in stress naïve mice induces social avoidance following subthreshold social defeat stress. Our studies uncover novel functions of MSN subtypes in depression-like outcomes. Notably, bidirectional alteration of D1-MSN activity promotes opposite behavioral outcomes to chronic social stress. Therefore, targeting D1-MSN activity may provide novel treatment strategies for depression or other affective disorders. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

Genetic selection for coping style predicts stressor susceptibility.

PubMed

Veenema, A H; Meijer, O C; de Kloet, E R; Koolhaas, J M

2003-03-01

Genetically selected aggressive (SAL) and nonaggressive (LAL) male wild house-mice which show distinctly different coping styles, also display a differential regulation of the hypothalamic-pituitary-adrenal axis after exposure to an acute stressor. To test the hypothesis that coping style predicts stressor susceptibility, the present study examined line differences in response to a chronic stressor. Chronic psychosocial stress was evoked using two paradigms. In the first paradigm, a SAL or LAL male was living in sensory contact (except tactile contact) with a dominant SAL male for 25 days (sensory contact stress). In the second paradigm, a SAL or LAL male was, in addition to the first paradigm, defeated by a SAL male for 21 consecutive days (defeat stress). The sensory contact stressor induced in LAL mice chronic body weight loss and increased plasma adrenocorticotropic hormone levels compared to SAL mice and increased corticosterone levels, thymus involution and lower hippocampal mineralocorticoid receptor (MR) : glucocorticoid receptor (GR) ratio compared to LAL controls. The defeat stressor increased corticosterone secretion and caused adrenal hypertrophy and thymus involution in both mouse lines. Defeated LAL mice showed long-lasting body weight loss and higher corticosterone concentrations than SAL mice and lower hippocampal MR : GR ratio and decreased immobility behaviour in the forced swimming test than LAL controls. Hypothalamic corticotropin-releasing hormone mRNA expression was higher in defeated SAL than in controls. The present data show that both stress paradigms induced line-dependent physiological and neuroendocrine changes, but that the sensory contact stressor produced chronic stress symptoms in LAL mice only. This latter stress paradigm therefore seems promising to analyse the role of genetic factors in the individual differences in stress-related psychopathology.

Computer-aided dental prostheses construction using reverse engineering.

PubMed

Solaberrieta, E; Minguez, R; Barrenetxea, L; Sierra, E; Etxaniz, O

2014-01-01

The implementation of computer-aided design/computer-aided manufacturing (CAD/CAM) systems with virtual articulators, which take into account the kinematics, constitutes a breakthrough in the construction of customised dental prostheses. This paper presents a multidisciplinary protocol involving CAM techniques to produce dental prostheses. This protocol includes a step-by-step procedure using innovative reverse engineering technologies to transform completely virtual design processes into customised prostheses. A special emphasis is placed on a novel method that permits a virtual location of the models. The complete workflow includes the optical scanning of the patient, the use of reverse engineering software and, if necessary, the use of rapid prototyping to produce CAD temporary prostheses.

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase.

PubMed

Fuertig, René; Azzinnari, Damiano; Bergamini, Giorgio; Cathomas, Flurin; Sigrist, Hannes; Seifritz, Erich; Vavassori, Stefano; Luippold, Andreas; Hengerer, Bastian; Ceci, Angelo; Pryce, Christopher R

2016-05-01

Psychosocial stress is a major risk factor for mood and anxiety disorders, in which excessive reactivity to aversive events/stimuli is a major psychopathology. In terms of pathophysiology, immune-inflammation is an important candidate, including high blood and brain levels of metabolites belonging to the kynurenine pathway. Animal models are needed to study causality between psychosocial stress, immune-inflammation and hyper-reactivity to aversive stimuli. The present mouse study investigated effects of psychosocial stress as chronic social defeat (CSD) versus control-handling (CON) on: Pavlovian tone-shock fear conditioning, activation of the kynurenine pathway, and efficacy of a specific inhibitor (IDOInh) of the tryptophan-kynurenine catabolising enzyme indoleamine 2,3-dioxygenase (IDO1), in reversing CSD effects on the kynurenine pathway and fear. CSD led to excessive fear learning and memory, whilst repeated oral escitalopram (antidepressant and anxiolytic) reversed excessive fear memory, indicating predictive validity of the model. CSD led to higher blood levels of TNF-α, IFN-γ, kynurenine (KYN), 3-hydroxykynurenine (3-HK) and kynurenic acid, and higher KYN and 3-HK in amygdala and hippocampus. CSD was without effect on IDO1 gene or protein expression in spleen, ileum and liver, whilst increasing liver TDO2 gene expression. Nonetheless, oral IDOInh reduced blood and brain levels of KYN and 3-HK in CSD mice to CON levels, and we therefore infer that CSD increases IDO1 activity by increasing its post-translational activation. Furthermore, repeated oral IDOInh reversed excessive fear memory in CSD mice to CON levels. IDOInh reversal of CSD-induced hyper-activity in the kynurenine pathway and fear system contributes significantly to the evidence for a causal pathway between psychosocial stress, immune-inflammation and the excessive fearfulness that is a major psychopathology in stress-related neuropsychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Defining Baconian Probability for Use in Assurance Argumentation

NASA Technical Reports Server (NTRS)

Graydon, Patrick J.

2016-01-01

The use of assurance cases (e.g., safety cases) in certification raises questions about confidence in assurance argument claims. Some researchers propose to assess confidence in assurance cases using Baconian induction. That is, a writer or analyst (1) identifies defeaters that might rebut or undermine each proposition in the assurance argument and (2) determines whether each defeater can be dismissed or ignored and why. Some researchers also propose denoting confidence using the counts of defeaters identified and eliminated-which they call Baconian probability-and performing arithmetic on these measures. But Baconian probabilities were first defined as ordinal rankings which cannot be manipulated arithmetically. In this paper, we recount noteworthy definitions of Baconian induction, review proposals to assess confidence in assurance claims using Baconian probability, analyze how these comport with or diverge from the original definition, and make recommendations for future practice.

Quiet Clean Short-Haul Experimental Engine (QCSEE) acoustic and aerodynamic tests on a scale model over-the-wing thrust reverser and forward thrust nozzle

NASA Technical Reports Server (NTRS)

Stimpert, D. L.

1978-01-01

An acoustic and aerodynamic test program was conducted on a 1/6.25 scale model of the Quiet, Clean, Short-Haul Experimental Engine (QCSEE) forward thrust over-the-wing (OTW) nozzle and OTW thrust reverser. In reverse thrust, the effect of reverser geometry was studied by parametric variations in blocker spacing, blocker height, lip angle, and lip length. Forward thrust nozzle tests determined the jet noise levels of the cruise and takeoff nozzles, the effect of opening side doors to achieve takeoff thrust, and scrubbing noise of the cruise and takeoff jet on a simulated wing surface. Velocity profiles are presented for both forward and reverse thrust nozzles. An estimate of the reverse thrust was made utilizing the measured centerline turning angle.

26 CFR 1.861-18 - Classification of transactions involving computer programs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... on a single disk for a one-time payment with restrictions on transfer and reverse engineering, which... license. The license is stated to be perpetual. Under the license no reverse engineering, decompilation... fee, on a World Wide Web home page on the Internet. P, the Country Z resident, in return for payment...

26 CFR 1.861-18 - Classification of transactions involving computer programs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... on a single disk for a one-time payment with restrictions on transfer and reverse engineering, which... license. The license is stated to be perpetual. Under the license no reverse engineering, decompilation... fee, on a World Wide Web home page on the Internet. P, the Country Z resident, in return for payment...

Recognition vs Reverse Engineering in Boolean Concepts Learning

ERIC Educational Resources Information Center

Shafat, Gabriel; Levin, Ilya

2012-01-01

This paper deals with two types of logical problems--recognition problems and reverse engineering problems, and with the interrelations between these types of problems. The recognition problems are modeled in the form of a visual representation of various objects in a common pattern, with a composition of represented objects in the pattern.…

Reverse Engineering Course at Philadelphia University in Jordan

ERIC Educational Resources Information Center

Younis, M. Bani; Tutunji, T.

2012-01-01

Reverse engineering (RE) is the process of testing and analysing a system or a device in order to identify, understand and document its functionality. RE is an efficient tool in industrial benchmarking where competitors' products are dissected and evaluated for performance and costs. RE can play an important role in the re-configuration and…

Teach CAD and Measuring Skills through Reverse Engineering

ERIC Educational Resources Information Center

Board, Keith

2012-01-01

This article describes a reverse engineering activity that gives students hands-on, minds-on experience with measuring tools, machine parts, and CAD. The author developed this activity to give students an abundance of practical experience with measuring tools. Equally important, it provides a good interface between the virtual world of CAD 3D…

A parallel implementation of the network identification by multiple regression (NIR) algorithm to reverse-engineer regulatory gene networks.

PubMed

Gregoretti, Francesco; Belcastro, Vincenzo; di Bernardo, Diego; Oliva, Gennaro

2010-04-21

The reverse engineering of gene regulatory networks using gene expression profile data has become crucial to gain novel biological knowledge. Large amounts of data that need to be analyzed are currently being produced due to advances in microarray technologies. Using current reverse engineering algorithms to analyze large data sets can be very computational-intensive. These emerging computational requirements can be met using parallel computing techniques. It has been shown that the Network Identification by multiple Regression (NIR) algorithm performs better than the other ready-to-use reverse engineering software. However it cannot be used with large networks with thousands of nodes--as is the case in biological networks--due to the high time and space complexity. In this work we overcome this limitation by designing and developing a parallel version of the NIR algorithm. The new implementation of the algorithm reaches a very good accuracy even for large gene networks, improving our understanding of the gene regulatory networks that is crucial for a wide range of biomedical applications.

A Predictive Approach to Network Reverse-Engineering

NASA Astrophysics Data System (ADS)

Wiggins, Chris

2005-03-01

A central challenge of systems biology is the ``reverse engineering" of transcriptional networks: inferring which genes exert regulatory control over which other genes. Attempting such inference at the genomic scale has only recently become feasible, via data-intensive biological innovations such as DNA microrrays (``DNA chips") and the sequencing of whole genomes. In this talk we present a predictive approach to network reverse-engineering, in which we integrate DNA chip data and sequence data to build a model of the transcriptional network of the yeast S. cerevisiae capable of predicting the response of genes in unseen experiments. The technique can also be used to extract ``motifs,'' sequence elements which act as binding sites for regulatory proteins. We validate by a number of approaches and present comparison of theoretical prediction vs. experimental data, along with biological interpretations of the resulting model. En route, we will illustrate some basic notions in statistical learning theory (fitting vs. over-fitting; cross- validation; assessing statistical significance), highlighting ways in which physicists can make a unique contribution in data- driven approaches to reverse engineering.

The selective reversible FAAH inhibitor, SSR411298, restores the development of maladaptive behaviors to acute and chronic stress in rodents.

PubMed

Griebel, Guy; Stemmelin, Jeanne; Lopez-Grancha, Mati; Fauchey, Valérie; Slowinski, Franck; Pichat, Philippe; Dargazanli, Gihad; Abouabdellah, Ahmed; Cohen, Caroline; Bergis, Olivier E

2018-02-05

Enhancing endogenous cannabinoid (eCB) signaling has been considered as a potential strategy for the treatment of stress-related conditions. Fatty acid amide hydrolase (FAAH) represents the primary degradation enzyme of the eCB anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). This study describes a potent reversible FAAH inhibitor, SSR411298. The drug acts as a selective inhibitor of FAAH, which potently increases hippocampal levels of AEA, OEA and PEA in mice. Despite elevating eCB levels, SSR411298 did not mimic the interoceptive state or produce the behavioral side-effects (memory deficit and motor impairment) evoked by direct-acting cannabinoids. When SSR411298 was tested in models of anxiety, it only exerted clear anxiolytic-like effects under highly aversive conditions following exposure to a traumatic event, such as in the mouse defense test battery and social defeat procedure. Results from experiments in models of depression showed that SSR411298 produced robust antidepressant-like activity in the rat forced-swimming test and in the mouse chronic mild stress model, restoring notably the development of inadequate coping responses to chronic stress. This preclinical profile positions SSR411298 as a promising drug candidate to treat diseases such as post-traumatic stress disorder, which involves the development of maladaptive behaviors.

Ideal Directed-Energy System To Defeat Small Unmanned Aircraft System Swarms

DTIC Science & Technology

2017-05-21

AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY IDEAL DIRECTED- ENERGY SYSTEM TO DEFEAT SMALL UNMANNED AIRCRAFT SYSTEM SWARMS by David F. Pina...directed energy (DE) developmental systems indicate this class of weapons is the best solution. A review of several continuous wave laser, pulsed high...powered microwave, and electronic warfare/jamming systems indicate the following attributes as ideal for a future directed energy weapon (DEW) system

Sex differences in cortisol's regulation of affiliative behavior.

PubMed

Sherman, Gary D; Rice, Leslie K; Jin, Ellie Shuo; Jones, Amanda C; Josephs, Robert A

2017-06-01

A contribution to a special issue on Hormones and Human Competition. A stress perspective is used to illuminate how competitive defeat and victory shape biology and behavior. We report a field study examining how change in cortisol following perceived defeat (vs. victory) in a competition-in this case, a dog agility competition-relates to affiliative behavior. Following competition, we measured cortisol change and the extent to which dog handlers directed affiliative behaviors toward their dogs. We found striking sex differences in affiliation. First, men were more affiliative toward their dogs after victory, whereas women were more affiliative after defeat. Second, the greater a female competitor's increase in cortisol, the more time she spent affiliating with her dog, whereas for men, the pattern was the exact opposite: the greater a male competitor's increase in cortisol, the less time he spent affiliating with his dog. This pattern suggests that, in the wake of competition, men and women's affiliative behavior may serve different functions-shared celebration for men; shared consolation for women. These sex differences show not only that men and women react very differently to victory and defeat, but also that equivalent changes in cortisol across the sexes are associated with strikingly different behavioral consequences for men and women. Copyright © 2016 Elsevier Inc. All rights reserved.

Making sense of misfortune: deservingness, self-esteem, and patterns of self-defeat.

PubMed

Callan, Mitchell J; Kay, Aaron C; Dawtry, Rael J

2014-07-01

Drawing on theorizing and research suggesting that people are motivated to view their world as an orderly and predictable place in which people get what they deserve, the authors proposed that (a) random and uncontrollable bad outcomes will lower self-esteem and (b) this, in turn, will lead to the adoption of self-defeating beliefs and behaviors. Four experiments demonstrated that participants who experienced or recalled bad (vs. good) breaks devalued their self-esteem (Studies 1a and 1b), and that decrements in self-esteem (whether arrived at through misfortune or failure experience) increase beliefs about deserving bad outcomes (Studies 1a, 1b, 2a, 2b). Five studies (Studies 3-7) extended these findings by showing that this, in turn, can engender a wide array of self-defeating beliefs and behaviors, including claimed self-handicapping ahead of an ability test (Study 3), the preference for others to view the self less favorably (Studies 4-5), chronic self-handicapping and thoughts of physical self-harm (Study 6), and choosing to receive negative feedback during an ability test (Study 7). The current findings highlight the important role that concerns about deservingness play in the link between lower self-esteem and patterns of self-defeating beliefs and behaviors. The theoretical and practical implications of these findings are discussed.

UAV Mission Optimization through Hybrid-Electric Propulsion

NASA Astrophysics Data System (ADS)

Blackwelder, Philip Scott

Hybrid-electric powertrain leverages the superior range of petrol based systems with the quiet and emission free benefits of electric propulsion. The major caveat to hybrid-electric powertrain in an airplane is that it is inherently heavier than conventional petroleum powertrain due mostly to the low energy density of battery technology. The first goal of this research is to develop mission planning code to match powertrain components for a small-scale unmanned aerial vehicle (UAV) to complete a standard surveillance mission within a set of user input parameters. The second goal is to promote low acoustic profile loitering through mid-flight engine starting. The two means by which midmission engine starting will be addressed is through reverse thrust from the propeller and a servo actuated gear to couple and decouple the engine and motor. The mission planning code calculates the power required to complete a mission and assists the user in sourcing powertrain components including the propeller, motor, battery, motor controller, engine and fuel. Reverse thrust engine starting involves characterizing an off the shelf variable pitch propeller and using its torque coefficient to calculate the advance ratio required to provide sufficient torque and speed to start an engine. Geared engine starting works like the starter in a conventional automobile. A servo actuated gear will couple the motor to the engine to start it and decouple once the engine has started. Reverse thrust engine starting was unsuccessful due to limitations of available off the shelf variable pitch propellers. However, reverse thrust engine starting could be realized through a custom larger diameter propeller. Geared engine starting was a success, though the system was unable to run fully as intended. Due to counter-clockwise crank rotation of the engine and the right-hand threads on the crankshaft, cranking the engine resulted in the nut securing the engine starter gear to back off as the engine cranked. A second nut was added to secure the starter gear but at the expense of removing the engine drive pulley. Removing the engine pulley meant that the starter gear must remain engaged to transmit torque to the propeller shaft as opposed to the engine pulley. This issue can be resolved using different hardware, however changing the mounting hardware would require additional modifications to the associated component which time would not permit. Though battery technology still proves to be the main constraint of electrified powertrain, careful design and mission planning can help minimize the weight penalties incurred. The mission planning code complements previous research by comparing the weight penalties of a blended climb versus an engine only climb and selecting the lightest option. Though reverse thrust engine starting proved unsuccessful, the success of geared engine starting now allows the engine to be shut off during loiter reducing both acoustic profile and fuel consumption during loiter.

Reversible Quantum Brownian Heat Engines for Electrons

NASA Astrophysics Data System (ADS)

Humphrey, T. E.; Newbury, R.; Taylor, R. P.; Linke, H.

2002-08-01

Brownian heat engines use local temperature gradients in asymmetric potentials to move particles against an external force. The energy efficiency of such machines is generally limited by irreversible heat flow carried by particles that make contact with different heat baths. Here we show that, by using a suitably chosen energy filter, electrons can be transferred reversibly between reservoirs that have different temperatures and electrochemical potentials. We apply this result to propose heat engines based on mesoscopic semiconductor ratchets, which can quasistatically operate arbitrarily close to Carnot efficiency.

Reversible quantum heat engines for electrons

NASA Astrophysics Data System (ADS)

Linke, Heiner; Humphrey, Tammy E.; Newbury, Richard; Taylor, Richard P.

2002-03-01

Brownian heat engines use local temperature gradients in asymmetric potentials to move particles against an external force. The energy efficiency of such machines is generally limited by irreversible heat flow carried by particles that make contact with different heat baths. Here we show that, by using a suitably chosen energy filter, electrons can be transferred reversibly between reservoirs that have different temperatures and electrochemical potentials. We apply this result to propose heat engines based on quantum ratchets, which can quasistatically operate at Carnot efficiency.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

REAR DETAIL OF RIGHT ENGINE AND WING. THRUST REVERSER REMAINS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

REAR DETAIL OF RIGHT ENGINE AND WING. THRUST REVERSER REMAINS OPEN. MECHANICS JONI BAINE (R) AND BILL THEODORE(L) OPEN FLAP CARRIAGE ACCESS WITH AN IMPACT GUN. THEY WILL CHECK TRANSMISSION FLUID AND OIL THE JACK SCREW. AT FAR LEFT UTILITY MECHANICS BEGIN BODY POLISHING. - Greater Buffalo International Airport, Maintenance Hangar, Buffalo, Erie County, NY

The Use of Reverse Engineering to Analyse Student Computer Programs.

ERIC Educational Resources Information Center

Vanneste, Philip; And Others

1996-01-01

Discusses how the reverse engineering approach can generate feedback on computer programs without the user having any prior knowledge of what the program was designed to do. This approach uses the cognitive model of programming knowledge to interpret both context independent and dependent errors in the same words and concepts as human programmers.…

An Application of Reverse Engineering to Automatic Item Generation: A Proof of Concept Using Automatically Generated Figures

ERIC Educational Resources Information Center

Lorié, William A.

2013-01-01

A reverse engineering approach to automatic item generation (AIG) was applied to a figure-based publicly released test item from the Organisation for Economic Cooperation and Development (OECD) Programme for International Student Assessment (PISA) mathematical literacy cognitive instrument as part of a proof of concept. The author created an item…

Over-the-wing model thrust reverser noise tests

NASA Technical Reports Server (NTRS)

Goodykoontz, J.; Gutierrez, O.

1977-01-01

Static acoustic tests were conducted on a 1/12 scale model over-the-wing target type thrust reverser. The model configuration simulates a design that is applicable to the over-the-wing short-haul advanced technology engine. Aerodynamic screening tests of a variety of reverser designs identified configurations that satisfied a reverse thrust requirement of 35 percent of forward thrust at a nozzle pressure ratio of 1.29. The variations in the reverser configuration included, blocker door angle, blocker door lip angle and shape, and side skirt shape. Acoustic data are presented and compared for the various configurations. The model data scaled to a single full size engine show that peak free field perceived noise (PN) levels at a 152.4 meter sideline distance range from 98 to 104 PNdb.

Mitigating the Backlash: US Airpower as a Military Instrument of Policy

DTIC Science & Technology

2003-06-01

maintain their preeminence by employing strategies based more on benevolence than coercion.”31 This is a key point , as it marks a line of departure...weapons are easily defeated with smoke or fire in the target area (to defeat laser designators and thermal imaging), by adequate concealment and...create decoy surface-to-air missiles (SAMs) and radars, some quite sophisticated, and to employ previously “strategic” (immobile, point -defense

Colombia’s FARC: More Than Just Opportunistic Criminals

DTIC Science & Technology

2013-02-14

principles, liberate the country from the ruling-class elites, and defeat the lawless national military. One of the United States’ staunchest allies...Colombian government, create a new state founded on Marxist-Leninist principles, liberate the country from the ruling-class elites, and defeat the lawless...power was concentrated in two highly-polarized political parties – the “ Liberals ” and the “Conservatives.”4 The struggle between the two parties was

On Culture: Know the Enemy and Know Thyself - Giap, Abrams, and Victory

DTIC Science & Technology

2016-05-26

be victorious, sometimes meet with defeat. One who knows neither the enemy nor himself will invariably be defeated in every engagement. ― Sun - Tzu , The...leader become “culturally astute” and for what purpose? Chinese military theorist Sun - Tzu provides an approach. Understanding culture, particularly...military organization, and personal identity. Sun - Tzu asserted that knowing oneself and one’s enemy could result in victory.4 Using an inductive

Defeat: A Motivation for Organizational Change?

DTIC Science & Technology

2007-03-28

GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Scott Carlson 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING...DEFEAT: A MOTIVATION FOR ORGANIZATIONAL CHANGE? The era of procrastinating , of half-measures, of soothing and baffling expedients, of delays, is...point has not worked in Iraq, as U.S. and coalition forces remain bogged down in what appears to be a long, protracted war that is making no apparent

Muslim Spirituality, Religious Coping, and Reactions to Terrorism Among Pakistani University Students.

PubMed

Khan, Ziasma Haneef; Watson, P J; Chen, Zhuo

2016-12-01

Pakistani Muslim university students (N = 207) displayed Personal Distress, Public Distress, and Personal Defeat Reactions to Terrorism. All three reactions predicted poorer mental health with Personal Defeat being especially disturbed in its adjustment implications. In line with the assumptions of coping theory, scores on the Negative Religious Coping Scale correlated positively with Personal Distress and with Personal Defeat. However, Positive Religious Coping, the spirituality of Muslim Experiential Religiousness, and the Intrinsic and Extrinsic Personal Religious Orientations exhibited positive rather than the expected negative linkages with Personal Distress and Public Distress. Muslim Experiential Religiousness moderated associations of Positive and Negative Religious Coping with Public Distress. When spirituality was high, these relationships were negative. When spirituality was low, they became positive. These data documented the negative impacts that terrorism can have on Pakistanis and suggested that Muslim religious commitments may have an important role to play in resisting those influences.

How Canada's Asbestos Industry Was Defeated in Quebec.

PubMed

Ruff, Kathleen

2017-02-01

Less than a decade ago, the Quebec asbestos industry enjoyed support from all the political parties in the Canadian House of Commons and the Quebec National Assembly, as well as from business and union organizations. Two lobby organizations (Chrysotile Institute and International Chrysotile Association) had significant global impact in promoting asbestos use and defeating asbestos ban efforts in developing countries. Quebec's two asbestos mines planned to expand operations and make Quebec the second biggest global asbestos exporter. With the aid of lobbyists, public relations consultants, and government financing, the asbestos industry came close to succeeding. The article examines how a campaign of international solidarity, involving scientific experts, asbestos victims, and health activists in Quebec, Canada, and overseas, succeeded in closing the two mines and defeating the political and social power that the Quebec asbestos industry had wielded for a century. This victory ended Canada's destructive role as global propagandist for the asbestos industry.

Evaluating a common semi-mechanistic mathematical model of gene-regulatory networks

PubMed Central

2015-01-01

Modeling and simulation of gene-regulatory networks (GRNs) has become an important aspect of modern systems biology investigations into mechanisms underlying gene regulation. A key challenge in this area is the automated inference (reverse-engineering) of dynamic, mechanistic GRN models from gene expression time-course data. Common mathematical formalisms for representing such models capture two aspects simultaneously within a single parameter: (1) Whether or not a gene is regulated, and if so, the type of regulator (activator or repressor), and (2) the strength of influence of the regulator (if any) on the target or effector gene. To accommodate both roles, "generous" boundaries or limits for possible values of this parameter are commonly allowed in the reverse-engineering process. This approach has several important drawbacks. First, in the absence of good guidelines, there is no consensus on what limits are reasonable. Second, because the limits may vary greatly among different reverse-engineering experiments, the concrete values obtained for the models may differ considerably, and thus it is difficult to compare models. Third, if high values are chosen as limits, the search space of the model inference process becomes very large, adding unnecessary computational load to the already complex reverse-engineering process. In this study, we demonstrate that restricting the limits to the [−1, +1] interval is sufficient to represent the essential features of GRN systems and offers a reduction of the search space without loss of quality in the resulting models. To show this, we have carried out reverse-engineering studies on data generated from artificial and experimentally determined from real GRN systems. PMID:26356485

Reverse engineering time discrete finite dynamical systems: a feasible undertaking?

PubMed

Delgado-Eckert, Edgar

2009-01-01

With the advent of high-throughput profiling methods, interest in reverse engineering the structure and dynamics of biochemical networks is high. Recently an algorithm for reverse engineering of biochemical networks was developed by Laubenbacher and Stigler. It is a top-down approach using time discrete dynamical systems. One of its key steps includes the choice of a term order, a technicality imposed by the use of Gröbner-bases calculations. The aim of this paper is to identify minimal requirements on data sets to be used with this algorithm and to characterize optimal data sets. We found minimal requirements on a data set based on how many terms the functions to be reverse engineered display. Furthermore, we identified optimal data sets, which we characterized using a geometric property called "general position". Moreover, we developed a constructive method to generate optimal data sets, provided a codimensional condition is fulfilled. In addition, we present a generalization of their algorithm that does not depend on the choice of a term order. For this method we derived a formula for the probability of finding the correct model, provided the data set used is optimal. We analyzed the asymptotic behavior of the probability formula for a growing number of variables n (i.e. interacting chemicals). Unfortunately, this formula converges to zero as fast as , where and . Therefore, even if an optimal data set is used and the restrictions in using term orders are overcome, the reverse engineering problem remains unfeasible, unless prodigious amounts of data are available. Such large data sets are experimentally impossible to generate with today's technologies.

Cranioplasty prosthesis manufacturing based on reverse engineering technology

PubMed Central

Chrzan, Robert; Urbanik, Andrzej; Karbowski, Krzysztof; Moskała, Marek; Polak, Jarosław; Pyrich, Marek

2012-01-01

Summary Background Most patients with large focal skull bone loss after craniectomy are referred for cranioplasty. Reverse engineering is a technology which creates a computer-aided design (CAD) model of a real structure. Rapid prototyping is a technology which produces physical objects from virtual CAD models. The aim of this study was to assess the clinical usefulness of these technologies in cranioplasty prosthesis manufacturing. Material/Methods CT was performed on 19 patients with focal skull bone loss after craniectomy, using a dedicated protocol. A material model of skull deficit was produced using computer numerical control (CNC) milling, and individually pre-operatively adjusted polypropylene-polyester prosthesis was prepared. In a control group of 20 patients a prosthesis was manually adjusted to each patient by a neurosurgeon during surgery, without using CT-based reverse engineering/rapid prototyping. In each case, the prosthesis was implanted into the patient. The mean operating times in both groups were compared. Results In the group of patients with reverse engineering/rapid prototyping-based cranioplasty, the mean operating time was shorter (120.3 min) compared to that in the control group (136.5 min). The neurosurgeons found the new technology particularly useful in more complicated bone deficits with different curvatures in various planes. Conclusions Reverse engineering and rapid prototyping may reduce the time needed for cranioplasty neurosurgery and improve the prosthesis fitting. Such technologies may utilize data obtained by commonly used spiral CT scanners. The manufacturing of individually adjusted prostheses should be commonly used in patients planned for cranioplasty with synthetic material. PMID:22207125

In vitro assessment of the contact mechanics of reverse-engineered distal humeral hemiarthroplasty prostheses.

PubMed

Willing, Ryan; Lapner, Michael; King, Graham J W; Johnson, James A

2014-11-01

Distal humeral hemiarthroplasty alters cartilage contact mechanics, which may predispose to osteoarthritis. Current prostheses do not replicate the native anatomy, and therefore contribute to these changes. We hypothesized that prostheses reverse-engineered from the native bone shape would provide similar contact patterns as the native articulation. Reverse-engineered hemiarthroplasty prostheses were manufactured for five cadaveric elbows based on CT images of the distal humerus. Passive flexion trials with constant muscle forces were performed with the native articulation intact while bone motions were recorded using a motion tracking system. Motion trials were then repeated after the distal humerus was replaced with a corresponding reverse-engineered prosthesis. Contact areas and patterns were reconstructed using computer models created from CT scan images combined with the motion tracker data. The total contact areas, as well as the contact area within smaller sub-regions of the ulna and radius, were analyzed for changes resulting from hemiarthroplasty using repeated-measures ANOVAs. Contact area at the ulna and radius decreased on average 42% (SD 19%, P=.008) and 41% (SD 42%, P=.096), respectively. Contact area decreases were not uniform throughout the different sub-regions, suggesting that contact patterns were also altered. Reverse-engineered prostheses did not reproduce the same contact pattern as the native joints, possibly because the thickness of the distal humerus cartilage layer was neglected when generating the prosthesis shapes or as a consequence of the increased stiffness of the metallic implants. Alternative design strategies and materials for hemiarthroplasty should be considered in future work. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reversible and irreversible heat engine and refrigerator cycles

NASA Astrophysics Data System (ADS)

Leff, Harvey S.

2018-05-01

Although no reversible thermodynamic cycles exist in nature, nearly all cycles covered in textbooks are reversible. This is a review, clarification, and extension of results and concepts for quasistatic, reversible and irreversible processes and cycles, intended primarily for teachers and students. Distinctions between the latter process types are explained, with emphasis on clockwise (CW) and counterclockwise (CCW) cycles. Specific examples of each are examined, including Carnot, Kelvin and Stirling cycles. For the Stirling cycle, potentially useful task-specific efficiency measures are proposed and illustrated. Whether a cycle behaves as a traditional refrigerator or heat engine can depend on whether it is reversible or irreversible. Reversible and irreversible-quasistatic CW cycles both satisfy Carnot's inequality for thermal efficiency, η ≤ η C a r n o t . Irreversible CCW cycles with two reservoirs satisfy the coefficient of performance inequality K ≤ K C a r n o t . However, an arbitrary reversible cycle satisfies K ≥ K C a r n o t when compared with a reversible Carnot cycle operating between its maximum and minimum temperatures, a potentially counterintuitive result.

The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom-Programmable Circuits

DTIC Science & Technology

2017-03-23

The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom- Programmable Circuits Raza Shafiq Hamid Mahmoodi Houman Homayoun Hassan... programmable circuits. While functionality of programmable cells are only known to trusted parties, effective techniques for activation and propagation...of the cells are introduced. The ATPG attack carefully studies dependency of programmable cells to develop their (partial) truth tables. Results

Israel Policy is Key to Defeating Islamic Extremists: A Coercive Solution to the Israeli-Palestinian Conflict

DTIC Science & Technology

2010-01-01

Israel Policy is Key to Defeating Islamic Extremists: A Coercive Solution to the Israeli-Palestinian Conflict Distribution A : Approved for...Unfortunately, continuation of the historical US position on the issue makes continuation of the conflict a dangerous national security risk to the US. This...paper will examine the conflict in light of US national security and propose that the current administration take a new approach to resolution in

China Naval Modernization: Implications for U.S. Navy Capabilities - Background and Issues for Congress

DTIC Science & Technology

2010-04-09

blunting the operations of those forces that do deploy forward. North Korea and Iran , as part of their defiance of international norms, are actively...section ‘Deter and Defeat Aggression in Anti-Access Environments,’ those are primarily capabilities needed for defeating China, not Iran , North Korea or... North Korea and Iran . John J. Tkacik, a former State Department China specialist, said the changes were probably ordered by the White House. "By

The Revolutionary Armed Forces of Colombia - People’s Army (FARC-EP): Marxist-Leninist Insurgency or Criminal Enterprise

DTIC Science & Technology

2005-12-01

to defeat the movement. This thesis draws heavily on Spanish - language analyses of the Colombian conflict and primary FARC-EP documents captured by...imminent defeat. 2 All translations from the Spanish are the author’s unless otherwise indicated. 10 Some observers have argued that the FARC-EP was...local, non- Spanish speaking, indigenous tribes or communities - also coexisted with the aforementioned groups. The interaction of the communists

Irregular Warfare as a National Military Strategy Approach for Small States

DTIC Science & Technology

2013-12-01

the most effective strategy for them. Analyses of large numbers of historical cases show that a conventional approach is a road to defeat for...this thesis is to illuminate the potential for small states to improve the effect of their military by adopting an irregular strategy. The thesis is... effective strategy for them. Analyses of large numbers of historical cases show that a conventional approach is a road to defeat for small states

Military Integration as a Factor for Post-Conflict Stability and Reconciliation: Rwanda, 1994-2005

DTIC Science & Technology

2006-09-01

VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave... manages defeat, shame, and remorse on the part of the loser. Therefore DDRI programs that integrate a sensitization program and exit strategy lead to...hatred; mitigates conflict influence factors; and manages defeat, shame, and remorse on the part of the loser. Therefore DDRI programs that integrate a

Joint Improvised Explosive Device Defeat Organization: Anomaly or Future Roadmap

DTIC Science & Technology

2008-03-25

fleet.45 He further relates that the submarine problem was analogous to “lifting an immense jellyfish .” No single answer could produce the complete...like that of lifting an immense jellyfish . Grasping it with two hands accomplishing nothing, but with hands-all-around and heaving together, one...can we lift the “immense jellyfish ” and hope to be successful. 20 Endnotes 1Rick Atkinson, “Left of Boom: The Struggle to Defeat Roadside Bombs

'Flash-forwards' and suicidal ideation: A prospective investigation of mental imagery, entrapment and defeat in a cohort from the Hong Kong Mental Morbidity Survey.

PubMed

Ng, Roger M K; Di Simplicio, Martina; McManus, Freda; Kennerley, Helen; Holmes, Emily A

2016-12-30

'Flash-forwards' - mental images of suicide - have been reported in selected Caucasian samples. Perceptions of defeat and entrapment are considered to be associated with suicidal ideation. We aimed to investigate (1) the presence of suicidal flash-forwards in people with recent suicidal ideation versus those without such ideation in an Asian sample, and (2) associations between suicidal flash-forwards, and perceptions of entrapment accounting for suicidal ideation. Eighty two suicidal and 80 non-suicidal participants from the Hong Kong Mental Morbidity Survey completed questionnaires including suicidal ideation, presence of suicidal flash-forward images, defeat and entrapment, at baseline and seven weeks later. Suicidal 'flash-forwards' were present only in suicidal cases. People with recent suicidal ideation and suicidal flash-forwards had more severe suicidal ideation than those without flash-forwards. Compared to those without suicidal ideation, people with recent suicidal ideation reported higher entrapment and defeat levels. Resolution of suicidal ideation over time was associated with fewer suicidal flash-forwards and reduced entrapment perceptions. At baseline and seven weeks, suicidal ideation was predicted by an interaction between suicidal flash-forwards presence and perceptions of entrapment. Mental imagery of suicide appears to be associated with suicidal ideation, and may represent a novel target in suicidal risk assessment and prevention. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Making Sense of Misfortune: Deservingness, Self-Esteem, and Patterns of Self-Defeat

PubMed Central

2014-01-01

Drawing on theorizing and research suggesting that people are motivated to view their world as an orderly and predictable place in which people get what they deserve, the authors proposed that (a) random and uncontrollable bad outcomes will lower self-esteem and (b) this, in turn, will lead to the adoption of self-defeating beliefs and behaviors. Four experiments demonstrated that participants who experienced or recalled bad (vs. good) breaks devalued their self-esteem (Studies 1a and 1b), and that decrements in self-esteem (whether arrived at through misfortune or failure experience) increase beliefs about deserving bad outcomes (Studies 1a, 1b, 2a, 2b). Five studies (Studies 3–7) extended these findings by showing that this, in turn, can engender a wide array of self-defeating beliefs and behaviors, including claimed self-handicapping ahead of an ability test (Study 3), the preference for others to view the self less favorably (Studies 4–5), chronic self-handicapping and thoughts of physical self-harm (Study 6), and choosing to receive negative feedback during an ability test (Study 7). The current findings highlight the important role that concerns about deservingness play in the link between lower self-esteem and patterns of self-defeating beliefs and behaviors. The theoretical and practical implications of these findings are discussed. PMID:24956317

Reverse engineering physical models employing a sensor integration between 3D stereo detection and contact digitization

NASA Astrophysics Data System (ADS)

Chen, Liang-Chia; Lin, Grier C. I.

1997-12-01

A vision-drive automatic digitization process for free-form surface reconstruction has been developed, with a coordinate measurement machine (CMM) equipped with a touch-triggered probe and a CCD camera, in reverse engineering physical models. The process integrates 3D stereo detection, data filtering, Delaunay triangulation, adaptive surface digitization into a single process of surface reconstruction. By using this innovative approach, surface reconstruction can be implemented automatically and accurately. Least-squares B- spline surface models with the controlled accuracy of digitization can be generated for further application in product design and manufacturing processes. One industrial application indicates that this approach is feasible, and the processing time required in reverse engineering process can be significantly reduced up to more than 85%.

Mobile Timekeeping Application Built on Reverse-Engineered JPL Infrastructure

NASA Technical Reports Server (NTRS)

Witoff, Robert J.

2013-01-01

Every year, non-exempt employees cumulatively waste over one man-year tracking their time and using the timekeeping Web page to save those times. This app eliminates this waste. The innovation is a native iPhone app. Libraries were built around a reverse- engineered JPL API. It represents a punch-in/punch-out paradigm for timekeeping. It is accessible natively via iPhones, and features ease of access. Any non-exempt employee can natively punch in and out, as well as save and view their JPL timecard. This app is built on custom libraries created by reverse-engineering the standard timekeeping application. Communication is through custom libraries that re-route traffic through BrowserRAS (remote access service). This has value at any center where employees track their time.

Synergistic Effects of Psychosocial Stress and Mild Peripheral Infection on Inducing Microglial Activation in the Hippocampal Dentate Gyrus and Long-Lasting Deficits in Hippocampus-Related Memory.

PubMed

Tzeng, Wen-Yu; Su, Chien-Chou; Sun, Li-Han; Cherng, Chianfang G.; Yu, Lung

2018-04-30

Lipopolysaccharide (LPS) treatment and stress may cause immune activation in the brain, an event which has been thought to play a role in mediating stress-induced cognitive dysfunction. However, the enduring impact of psychosocial stress on brain immune activation or cognitive deficits has not been well investigated. Likewise, it remains unexplored whether there exist synergistic effects of psychosocial stress and a weak systemic LPS treatment on brain immune activation and/or cognitive function. In this work, a 10-day social defeat regimen was used to model psychosocial stress and the number and density of ionized calcium-binding adaptor molecule 1 (Iba1)-stained microglia was used to reveal brain immune activation in male Balb/C mice. The social defeat regimen did not cause observable microglial activation in dentate gyrus (DG) 24 h after the conclusion of the regimen. Microglial activation peaked in DG 24 h following a single 1 mg/kg intra-peritoneal LPS injection. At this time point, DG microglial activation was not evident providing 0.125 mg/kg or lower of LPS was used, this dose of LPS was, thus, regarded as the “sub-threshold” in this study. Twenty-four h after the conclusion of the defeat regimen, mice received a social interaction test to determine their defeat stress susceptibility and a “sub-threshold” LPS injection. DG microglial activation was observed in the defeat-stress susceptible, but not in the resilient, mice. Furthermore, the stress-susceptible mice showed impairment in object location and Y maze tasks 24 and 72 h after the “sub-threshold” LPS injection. These results suggest that psychosocial stress, when combined with a negligible peripheral infection, may induce long-lasting hippocampus-related memory deficits exclusively in subjects susceptible to psychosocial stresses.

SKF83959 Produces Antidepressant Effects in a Chronic Social Defeat Stress Model of Depression through BDNF-TrkB Pathway

PubMed Central

Jiang, Bo; Wang, Fang; Yang, Si; Fang, Peng; Deng, Zhi-Fang; Xiao, Jun-Li; Hu, Zhuang-Li

2015-01-01

Background: SKF83959 stimulates the phospholipase Cβ/inositol phosphate 3 pathway, resulting in the activation of Ca2+/calmodulin-dependent kinase IIα, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. Methods: In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. Results: We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine D5 receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase IIα pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. Conclusion: These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal D5/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway. PMID:25522427

Countermeasures to the US National Missile Defense

NASA Astrophysics Data System (ADS)

Gronlund, Lisbeth

2001-04-01

One of the key technical questions about national missile defenses is whether they can be expected to work under real-world conditions if the attacker takes steps to defeat the defense. This talk will discuss steps that an emerging missile state could take to confuse, overwhelm, or otherwise defeat the planned US NMD system developed by the Clinton administration. It will consider three such ``countermeasures" that would be within the technical capability of a state that could develop and deploy a long-range missile capable of reaching the United States, which is the threat the NMD system is intended to defend against. The talk will be based on the April 2000 report ``Countermeasures: A Technical Evaluation of the Operational Effectiveness of the Planned US National Missile Defense System," which was co-authored by the speaker and 10 other physicists and engineers. Although the talk will refer to the ground-based NMD system under development, the conclusions are applicable to any mid-course NMD system using hit-to-kill infrared-homing interceptors, regardless of their basing mode. The three countermeasures considered are: (1) biological weapons deployed on 100 or more small bomblets, or submunitions, that would be released shortly after the boost phase; (2) nuclear warheads with anti-simulation balloon decoys, in which the attacker disguises the warhead by enclosing it in an aluminum-coated mylar balloon and releasing it along with a large number of otherwise similar but empty balloons; and (3) nuclear warheads with cooled shrouds, in which the attacker foils the kill vehicle's homing process by covering each nuclear warhead with a double-walled cone containing liquid nitrogen.

Strategic Dissonance RPA Tactics To Defeat Al Qaeda

DTIC Science & Technology

2015-11-24

Pakistan NDU Journal XXVIII (2014): 77- 86. http://www.ndu.edu.pk/issra/issra_pub/2014/NDU-Journal-2014.pdf. Maass, Matthias. “From U - 2s to Drones: U.S...accordance with Air Force Instruction 51-303, it is not copyrighted, but is the property of the United States government. iii Biography Mr... aircraft (RPA) as the primary means to defeat al-Qaeda is failing. The tactic is a convenient weapon of choice because it is accurate, low risk, and

Doctrines of Defeat, La Guerre Revolutionnaire and Counterinsurgency Warfare

DTIC Science & Technology

1992-12-01

sending in colonial troops to "pacify" the region. The French simply felt a superior force of arms would regain control. As France began to see defeat at...doctrine. The French Army’s isolation from its own society was the result of many reasons. At the end of World War II, France was war weary; it had...strategically defensive by threateni.,. nuclear destruction of an enemy’s force attempting _o invade France or her allies. In theory, all French

Energy Efficient Engine program advanced turbofan nacelle definition study

NASA Technical Reports Server (NTRS)

Howe, David C.; Wynosky, T. A.

1985-01-01

Advanced, low drag, nacelle configurations were defined for some of the more promising propulsion systems identified in the earlier Benefit/Cost Study, to assess the benefits associated with these advanced technology nacelles and formulate programs for developing these nacelles and low volume thrust reversers/spoilers to a state of technology readiness in the early 1990's. The study results established the design feasibility of advanced technology, slim line nacelles applicable to advanced technology, high bypass ratio turbofan engines. Design feasibility was also established for two low volume thrust reverse/spoiler concepts that meet or exceed the required effectiveness for these engines. These nacelle and thrust reverse/spoiler designs were shown to be applicable in engines with takeoff thrust sizes ranging from 24,000 to 60,000 pounds. The reduced weight, drag, and cost of the advanced technology nacelle installations relative to current technology nacelles offer a mission fuel burn savings ranging from 3.0 to 4.5 percent and direct operating cost plus interest improvements from 1.6 to 2.2 percent.

CRISPR: a Versatile Tool for Both Forward and Reverse Genetics Research

PubMed Central

Gurumurthy, Channabasavaiah B.; Grati, M'hamed; Ohtsuka, Masato; Schilit, Samantha L.P.; Quadros, Rolen M.; Liu, Xue Zhong

2016-01-01

Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system, which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples. PMID:27384229

The results of a low-speed wind tunnel test to investigate the effects of the Refan JT8D engine target thrust reverser on the stability and control characteristics of the Boeing 727-200 airplane

NASA Technical Reports Server (NTRS)

Kupcis, E. A.

1974-01-01

The effects of the Refan JT8D side engine target thrust reverser on the stability and control characteristics of the Boeing 727-200 airplane were investigated using the Boeing-Vertol 20 x 20 ft Low-Speed Wind Tunnel. A powered model of the 727-200 was tested in groud effect in the landing configuration. The Refan target reverser configuration was evaluated relative to the basic production 727 airplane with its clamshell-deflector door thrust reverser design. The Refan configuration had slightly improved directional control characteristics relative to the basic airplane. Clocking the Refan thrust reversers 20 degrees outboard to direct the reverser flow away from the vertical tail, had little effect on directional control. However, clocking them 20 degrees inboard resulted in a complete loss of rudder effectiveness for speeds greater than 90 knots. Variations in Refan reverser lip/fence geometry had a minor effect on directional control.

Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

PubMed

Wen, Shameng; Meng, Qingkun; Feng, Chao; Tang, Chaojing

2017-01-01

Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

A Survey of Statistical Models for Reverse Engineering Gene Regulatory Networks

PubMed Central

Huang, Yufei; Tienda-Luna, Isabel M.; Wang, Yufeng

2009-01-01

Statistical models for reverse engineering gene regulatory networks are surveyed in this article. To provide readers with a system-level view of the modeling issues in this research, a graphical modeling framework is proposed. This framework serves as the scaffolding on which the review of different models can be systematically assembled. Based on the framework, we review many existing models for many aspects of gene regulation; the pros and cons of each model are discussed. In addition, network inference algorithms are also surveyed under the graphical modeling framework by the categories of point solutions and probabilistic solutions and the connections and differences among the algorithms are provided. This survey has the potential to elucidate the development and future of reverse engineering GRNs and bring statistical signal processing closer to the core of this research. PMID:20046885

Tobacco control and direct democracy in Dade County, Florida: future implications for health advocates.

PubMed

Givel, M S; Glantz, S A

2000-01-01

In 1979 and 1980 in Dade County, Florida, a small grassroots advocacy group, Group Against Smoking Pollution (GASP), attempted to enact a clean indoor air ordinance through the initiative process. The tobacco industry's successful efforts to defeat the initiatives were expensive high-tech media-centered campaigns. Even though GASP's electoral resources were extremely limited for both initiatives, GASP utilized similar media-centered tactics. This approach attempted to defeat the tobacco industry in its own venue, in spite of the tobacco industry's vastly greater resources. Nevertheless, the industry defeated these ordinances by narrow margins because of broad voter support for the initiatives before the industry started its campaigns. Health advocates will never have the resources to match the tobacco industry in expensive high-tech media-centered initiative campaigns. Rather, their power lies in the general popularity of tobacco control legislation and their ability to mobilize broad grassroots efforts combined with an adequately funded media campaign.

Nanostructured thermites based on iodine pentoxide for bio agent defeat systems.

NASA Astrophysics Data System (ADS)

Hobosyan, Mkhitar; Kazansky, Alexander; Martirosyan, Karen

2011-10-01

The risk for bioterrorist events involving the intentional airborne release of contagious agents has led to development of new approaches for bio agent defeat technologies both indoors and outdoors. Novel approaches to defeat harmful biological agents have generated a strong demand for new active materials. The preferred solutions are to neutralize the biological agents within the immediate target area by using aerosolized biocidal substances released in situ by high energetic reactions. By using nano-thermite reactions, with energy release up to 25 kJ/cc, based on I2O5/Al nanoparticles we intend to generate high quantity of vaporized iodine for spatial deposition onto harmful bacteria for their destruction. In this report, the effect of reaction product on growth and survival of Escherichia coli (E-coli) expressing GFP (Green Fluorescent Protein) was investigated. Moreover, we developed an approach to increase sensitivity of the detection. The study has shown that I2O5/Al nanosystem is extremely effective to disinfect harmful biological agents such (E-coli) bacteria in seconds.

Reverse engineering of integrated circuits

DOEpatents

Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

2003-01-01

Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

The acute social defeat stress and nest-building test paradigm: A potential new method to screen drugs for depressive-like symptoms.

PubMed

Otabi, Hikari; Goto, Tatsuhiko; Okayama, Tsuyoshi; Kohari, Daisuke; Toyoda, Atsushi

2017-02-01

Psychosocial stress can cause mental conditions such as depression in humans. To develop drug therapies for the treatment of depression, it is necessary to use animal models of depression to screen drug candidates that exhibit anti-depressive effects. Unfortunately, the present methods of drug screening for antidepressants, the forced-swim test and tail-suspension test, are limiting factors in drug discovery because they are not based on the constructive validity of objective phenotypes in depression. Previously, we discovered that the onset of nest building is severely delayed in mice exposed to subchronic mild social defeat stress (sCSDS). Therefore, a novel paradigm combining acute social defeat stress (ASDS) and the nest-building test (SNB) were established for the efficient screening of drugs for depressive-like symptoms. Since ASDS severely delayed the nest-building process as shown in chronically social defeated mice, we sought to rescue the delayed nest-building behavior in ASDS mice. Injecting a specific serotonin 2a receptor antagonist (SR-46349B), the nest-building deficit exhibited by ASDS mice was partially rescued. On the other hand, a selective serotonin reuptake inhibitor (fluoxetine) did not rescue the nest-building deficit in ASDS mice. Therefore, we conclude that the SNB paradigm is an another potential behavioral method for screening drugs for depressive-like symptoms including attention deficit, anxiety, low locomotion, and decreased motivation. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantum Stirling heat engine and refrigerator with single and coupled spin systems

NASA Astrophysics Data System (ADS)

Huang, Xiao-Li; Niu, Xin-Ya; Xiu, Xiao-Ming; Yi, Xue-Xi

2014-02-01

We study the reversible quantum Stirling cycle with a single spin or two coupled spins as the working substance. With the single spin as the working substance, we find that under certain conditions the reversed cycle of a heat engine is NOT a refrigerator, this feature holds true for a Stirling heat engine with an ion trapped in a shallow potential as its working substance. The efficiency of quantum Stirling heat engine can be higher than the efficiency of the Carnot engine, but the performance coefficient of the quantum Stirling refrigerator is always lower than its classical counterpart. With two coupled spins as the working substance, we find that a heat engine can turn to a refrigerator due to the increasing of the coupling constant, this can be explained by the properties of the isothermal line in the magnetic field-entropy plane.

Agent of opportunity risk mitigation: people, engineering, and security efficacy.

PubMed

Graham, Margaret E; Tunik, Michael G; Farmer, Brenna M; Bendzans, Carly; McCrillis, Aileen M; Nelson, Lewis S; Portelli, Ian; Smith, Silas; Goldberg, Judith D; Zhang, Meng; Rosenberg, Sheldon D; Goldfrank, Lewis R

2010-12-01

Agents of opportunity (AO) are potentially harmful biological, chemical, radiological, and pharmaceutical substances commonly used for health care delivery and research. AOs are present in all academic medical centers (AMC), creating vulnerability in the health care sector; AO attributes and dissemination methods likely predict risk; and AMCs are inadequately secured against a purposeful AO dissemination, with limited budgets and competing priorities. We explored health care workers' perceptions of AMC security and the impact of those perceptions on AO risk. Qualitative methods (survey, interviews, and workshops) were used to collect opinions from staff working in a medical school and 4 AMC-affiliated hospitals concerning AOs and the risk to hospital infrastructure associated with their uncontrolled presence. Secondary to this goal, staff perception concerning security, or opinions about security behaviors of others, were extracted, analyzed, and grouped into themes. We provide a framework for depicting the interaction of staff behavior and access control engineering, including the tendency of staff to "defeat" inconvenient access controls. In addition, 8 security themes emerged: staff security behavior is a significant source of AO risk; the wide range of opinions about "open" front-door policies among AMC staff illustrates a disparity of perceptions about the need for security; interviewees expressed profound skepticism concerning the effectiveness of front-door access controls; an AO risk assessment requires reconsideration of the security levels historically assigned to areas such as the loading dock and central distribution sites, where many AOs are delivered and may remain unattended for substantial periods of time; researchers' view of AMC security is influenced by the ongoing debate within the scientific community about the wisdom of engaging in bioterrorism research; there was no agreement about which areas of the AMC should be subject to stronger access controls; security personnel play dual roles of security and customer service, creating the negative perception that neither role is done well; and budget was described as an important factor in explaining the state of security controls. We determined that AMCs seeking to reduce AO risk should assess their institutionally unique AO risks, understand staff security perceptions, and install access controls that are responsive to the staff's tendency to defeat them. The development of AO attribute fact sheets is desirable for AO risk assessment; new funding and administrative or legislative tools to improve AMC security are required; and security practices and methods that are convenient and effective should be engineered.

Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles.

PubMed

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Vialou, Vincent; Heller, Elizabeth A; Yieh, Lynn; LaBonté, Benoit; Peña, Catherine J; Shen, Li; Wittenberg, Gayle M; Nestler, Eric J

2017-02-15

Examining transcriptional regulation by antidepressants in key neural circuits implicated in depression and understanding the relation to transcriptional mechanisms of susceptibility and natural resilience may help in the search for new therapeutic agents. Given the heterogeneity of treatment response in human populations, examining both treatment response and nonresponse is critical. We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine, and a rapidly acting, non-monoamine-based antidepressant, ketamine, in mice subjected to chronic social defeat stress, a validated depression model, and used RNA sequencing to analyze transcriptional profiles associated with susceptibility, resilience, and antidepressant response and nonresponse in the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. We identified similar numbers of responders and nonresponders after ketamine or imipramine treatment. Ketamine induced more expression changes in the hippocampus; imipramine induced more expression changes in the nucleus accumbens and amygdala. Transcriptional profiles in treatment responders were most similar in the PFC. Nonresponse reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptibility-associated transcriptional changes and induced resilience-associated transcription in the PFC. We generated a uniquely large resource of gene expression data in four interconnected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by antidepressant drugs and in both reversing susceptibility- and inducing resilience-associated molecular adaptations. In addition, we found region-specific effects of each drug, suggesting both common and unique effects of imipramine versus ketamine. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Using a Formal Approach for Reverse Engineering and Design Recovery to Support Software Reuse

NASA Technical Reports Server (NTRS)

Gannod, Gerald C.

2002-01-01

This document describes 3rd year accomplishments and summarizes overall project accomplishments. Included as attachments are all published papers from year three. Note that the budget for this project was discontinued after year two, but that a residual budget from year two allowed minimal continuance into year three. Accomplishments include initial investigations into log-file based reverse engineering, service-based software reuse, and a source to XML generator.

Variable Cycle Intake for Reverse Core Engine

NASA Technical Reports Server (NTRS)

Chandler, Jesse M (Inventor); Staubach, Joseph B (Inventor); Suciu, Gabriel L (Inventor)

2016-01-01

A gas generator for a reverse core engine propulsion system has a variable cycle intake for the gas generator, which variable cycle intake includes a duct system. The duct system is configured for being selectively disposed in a first position and a second position, wherein free stream air is fed to the gas generator when in the first position, and fan stream air is fed to the gas generator when in the second position.

A new digitized reverse correction method for hypoid gears based on a one-dimensional probe

NASA Astrophysics Data System (ADS)

Li, Tianxing; Li, Jubo; Deng, Xiaozhong; Yang, Jianjun; Li, Genggeng; Ma, Wensuo

2017-12-01

In order to improve the tooth surface geometric accuracy and transmission quality of hypoid gears, a new digitized reverse correction method is proposed based on the measurement data from a one-dimensional probe. The minimization of tooth surface geometrical deviations is realized from the perspective of mathematical analysis and reverse engineering. Combining the analysis of complex tooth surface generation principles and the measurement mechanism of one-dimensional probes, the mathematical relationship between the theoretical designed tooth surface, the actual machined tooth surface and the deviation tooth surface is established, the mapping relation between machine-tool settings and tooth surface deviations is derived, and the essential connection between the accurate calculation of tooth surface deviations and the reverse correction method of machine-tool settings is revealed. Furthermore, a reverse correction model of machine-tool settings is built, a reverse correction strategy is planned, and the minimization of tooth surface deviations is achieved by means of the method of numerical iterative reverse solution. On this basis, a digitized reverse correction system for hypoid gears is developed by the organic combination of numerical control generation, accurate measurement, computer numerical processing, and digitized correction. Finally, the correctness and practicability of the digitized reverse correction method are proved through a reverse correction experiment. The experimental results show that the tooth surface geometric deviations meet the engineering requirements after two trial cuts and one correction.

Piles of defeat. Napoleon at Waterloo.

PubMed

Welling, D R; Wolff, B G; Dozois, R R

1988-04-01

Major events of history have frequently turned on seemingly trivial matters. One such situation involves Napoleon Bonaparte at Waterloo. Napoleon was not feeling well on the day of the battle of Waterloo, despite fighting well at Ligny, a few days before the last, dramatic June 18 battle. There is considerable indication that Napoleon was bothered by very painful thrombosed hemorrhoids. Did this affect his generalship that day? What is the evidence that Napoleon was afflicted with thrombosed hemorrhoids? What contribution could this factor have made to the French defeat at Waterloo?

Techniques utilized in the simulated altitude testing of a 2D-CD vectoring and reversing nozzle

NASA Technical Reports Server (NTRS)

Block, H. Bruce; Bryant, Lively; Dicus, John H.; Moore, Allan S.; Burns, Maureen E.; Solomon, Robert F.; Sheer, Irving

1988-01-01

Simulated altitude testing of a two-dimensional, convergent-divergent, thrust vectoring and reversing exhaust nozzle was accomplished. An important objective of this test was to develop test hardware and techniques to properly operate a vectoring and reversing nozzle within the confines of an altitude test facility. This report presents detailed information on the major test support systems utilized, the operational performance of the systems and the problems encountered, and test equipment improvements recommended for future tests. The most challenging support systems included the multi-axis thrust measurement system, vectored and reverse exhaust gas collection systems, and infrared temperature measurement systems used to evaluate and monitor the nozzle. The feasibility of testing a vectoring and reversing nozzle of this type in an altitude chamber was successfully demonstrated. Supporting systems performed as required. During reverser operation, engine exhaust gases were successfully captured and turned downstream. However, a small amount of exhaust gas spilled out the collector ducts' inlet openings when the reverser was opened more than 60 percent. The spillage did not affect engine or nozzle performance. The three infrared systems which viewed the nozzle through the exhaust collection system worked remarkably well considering the harsh environment.

77 FR 40026 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... and contractor logistics, Quality Assurance Team support services, engineering and technical support..., engineering and technical support, and other related elements of program support. The estimated cost is $49..., maintenance, or training is Confidential. Reverse engineering could reveal Confidential information...

Social defeat stress promotes tumor growth and angiogenesis by upregulating vascular endothelial growth factor/extracellular signal-regulated kinase/matrix metalloproteinase signaling in a mouse model of lung carcinoma.

PubMed

Wu, Xiao; Liu, Bao-Jun; Ji, Shumeng; Wu, Jing-Feng; Xu, Chang-Qing; Du, Yi-Jie; You, Xiao-Fang; Li, Bei; Le, Jing-Jing; Xu, Hai-Lin; Duan, Xiao-Hong; Dong, Jing-Cheng

2015-07-01

Numerous epidemiological and experimental animal studies have indicated that chronic psychological stress may promote tumor development. However, the underlying molecular mechanisms by which chronic stress promotes tumorigenesis remain to be fully elucidated and animal models have not yet been well established. In the present study, an established mouse model of repeated social defeat stress (RSDS), was generated and used to investigate the effect of stress on tumor growth and metastasis. C57BL/6 mice were exposed to RSDS for 10 days, followed by subcutaneousl inoculation with Lewis lung carcinoma cells for seven days. The tumor weight and volume as well as the number of the lung metastatic nodules were then determined. Vascular endothelial growth factor (VEGF) serum levels were measured using ELISAs. In addition, expression levels of VEGF receptor (VEGFR) and L1 cell adhesion molecule (L1CAM) messenger (m)RNA were confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, protein expression levels of phosphorlyated extracellular signal-regulated kinase (pERK), matrix metalloproteinase (MMP)-2 and MMP-9 were examined using western blot analysis. The results showed that RSDS significantly increased the weight and the volume of the primary tumor as well as the number of the lung metastatic nodules. Serum VEGF levels were significantly higher in the tumor-stress group compared with those of the unstressed tumor mice. In addition, tumors in stressed animals demonstrated markedly enhanced expression of VEGFR-2 and L1CAM mRNA as well as pERK, MMP-2 and MMP-9 protein expression. In conclusion, these results suggested that RSDS contributed to lung cancer progression, angiogenesis and metastasis, which was partially associated with increased VEGF secretion and therefore the activation of the ERK signaling pathway, resulting in the induction of MMP-2 and MMP-9 protein expression.

Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress☆

PubMed Central

Hanke, M.L.; Powell, N.D.; Stiner, L.M.; Bailey, M.T.; Sheridan, J.F.

2012-01-01

During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic–pituitary–adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b+ splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18 h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b+ cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation. PMID:22841997

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake.

PubMed

Albrechet-Souza, Lucas; Viola, Thiago W; Grassi-Oliveira, Rodrigo; Miczek, Klaus A; de Almeida, Rosa M M

2017-01-01

Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF) neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST) contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume) for 4 weeks, control and stressed mice had CRF type 1 (CRFR1) or type 2 (CRFR2) receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2 . Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates alcohol consumption in both socially defeated and non-stressed mice with a history of chronic intake.

CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES: Research on reverse recovery characteristics of SiGeC p-i-n diodes

NASA Astrophysics Data System (ADS)

Gao, Yong; Liu, Jing; Yang, Yuan

2008-12-01

This paper analyses the reverse recovery characteristics and mechanism of SiGeC p-i-n diodes. Based on the integrated systems engineering (ISE) data, the critical physical models of SiGeC diodes are proposed. Based on hetero-junction band gap engineering, the softness factor increases over six times, reverse recovery time is over 30% short and there is a 20% decrease in peak reverse recovery current for SiGeC diodes with 20% of germanium and 0.5% of carbon, compared to Si diodes. Those advantages of SiGeC p-i-n diodes are more obvious at high temperature. Compared to lifetime control, SiGeC technique is more suitable for improving diode properties and the tradeoff between reverse recovery time and forward voltage drop can be easily achieved in SiGeC diodes. Furthermore, the high thermal-stability of SiGeC diodes reduces the costs of further process steps and offers more freedoms to device design.

A novel technique for presurgical nasoalveolar molding using computer-aided reverse engineering and rapid prototyping.

PubMed

Yu, Quan; Gong, Xin; Wang, Guo-Min; Yu, Zhe-Yuan; Qian, Yu-Fen; Shen, Gang

2011-01-01

To establish a new method of presurgical nasoalveolar molding (NAM) using computer-aided reverse engineering and rapid prototyping technique in infants with unilateral cleft lip and palate (UCLP). Five infants (2 males and 3 females with mean age of 1.2 w) with complete UCLP were recruited. All patients were subjected to NAM before the cleft lip repair. The upper denture casts were recorded using a three-dimensional laser scanner within 2 weeks after birth in UCLP infants. A digital model was constructed and analyzed to simulate the NAM procedure with reverse engineering software. The digital geometrical data were exported to print the solid model with rapid prototyping system. The whole set of appliances was fabricated based on these solid models. Laser scanning and digital model construction simplified the NAM procedure and estimated the treatment objective. The appliances were fabricated based on the rapid prototyping technique, and for each patient, the complete set of appliances could be obtained at one time. By the end of presurgical NAM treatment, the cleft was narrowed, and the malformation of nasoalveolar segments was aligned normally. We have developed a novel technique of presurgical NAM based on a computer-aided design. The accurate digital denture model of UCLP infants could be obtained with laser scanning. The treatment design and appliance fabrication could be simplified with a computer-aided reverse engineering and rapid prototyping technique.

Reduced Orexin System Function Contributes to Resilience to Repeated Social Stress.

PubMed

Grafe, Laura A; Eacret, Darrell; Dobkin, Jane; Bhatnagar, Seema

2018-01-01

Exposure to stress increases the risk of developing affective disorders such as depression and post-traumatic stress disorder (PTSD). However, these disorders occur in only a subset of individuals, those that are more vulnerable to the effects of stress, whereas others remain resilient. The coping style adopted to deal with the stressor, either passive or active coping, is related to vulnerability or resilience, respectively. Important neural substrates that mediate responses to a stressor are the orexins. These neuropeptides are altered in the cerebrospinal fluid of patients with stress-related illnesses such as depression and PTSD. The present experiments used a rodent social defeat model that generates actively coping rats and passively coping rats, which we have previously shown exhibit resilient and vulnerable profiles, respectively, to examine if orexins play a role in these stress-induced phenotypes. In situ radiolabeling and qPCR revealed that actively coping rats expressed significantly lower prepro-orexin mRNA compared with passively coping rats. This led to the hypothesis that lower levels of orexins contribute to resilience to repeated social stress. To test this hypothesis, rats first underwent 5 d of social defeat to establish active and passive coping phenotypes. Then, orexin neurons were inhibited before each social defeat for three additional days using designer receptors exclusively activated by designer drugs (DREADDs). Inhibition of orexins increased social interaction behavior and decreased depressive-like behavior in the vulnerable population of rats. Indeed, these data suggest that lowering orexins promoted resilience to social defeat and may be an important target for treatment of stress-related disorders.

Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.

PubMed

Der-Avakian, Andre; D'Souza, Manoranjan S; Potter, David N; Chartoff, Elena H; Carlezon, William A; Pizzagalli, Diego A; Markou, Athina

2017-05-01

Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders. Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum. Adult male Wistar rats were trained on an operant probabilistic reward task (PRT) and then exposed to 3 days of social defeat before assessment of reward learning. After testing, the ACC, VTA, and striatum were dissected, and expression of genes previously implicated in stress was assessed. Social defeat blunted reward learning (manifested as reduced response bias toward a more frequently rewarded stimulus) and was associated with increased nociceptin/orphanin FQ (N/OFQ) peptide mRNA levels in the striatum and decreased Fos mRNA levels in the VTA. Moreover, N/OFQ peptide and nociceptin receptor mRNA levels in the ACC, VTA and striatum were inversely related to reward learning. The behavioral findings parallel previous data in humans, suggesting that stress similarly disrupts reward learning in both species. Increased striatal N/OFQ mRNA in stressed rats characterized by impaired reward learning is consistent with accumulating evidence that antagonism of nociceptin receptors, which bind N/OFQ, has antidepressant-like effects. These results raise the possibility that nociceptin systems represent a molecular substrate through which stress produces reward learning deficits in mood disorders.

Validation of a Spanish language version of the pain self-perception scale in patients with fibromyalgia

PubMed Central

2010-01-01

Background The Pain Self-Perception Scale (PSPS) is a 24-item questionnaire used to assess mental defeat in chronic pain patients. The aim of this study was to develop a Spanish language version of the PSPS (PSPS-Spanish), to assess the instrument's psychometric properties in a sample of patients with fibromyalgia and to confirm a possible overlapping between mental defeat and pain catastrophizing. Methods The PSPS was translated into Spanish by three bilingual content and linguistic experts, and then back-translated into English to assess for equivalence. The final Spanish version was administered, along with the Hospital Anxiety Depression Scale (HADS), Pain Visual Analogue Scale (PVAS), Pain Catastrophizing Scale (PCS) and Fibromyalgia Impact Questionnaire (FIQ), to 250 Spanish patients with fibromyalgia. Results PSPS-Spanish was found to have high internal consistency (Cronbach's α = 0.90 and the item-total r correlation coefficients ranged between 0.68 and 0.86). Principal components analysis revealed a one-factor structure which explained 61.4% of the variance. The test-retest correlation assessed with the intraclass correlation coefficient, over a 1-2 weeks interval, was 0.78. The total PSPS score was significantly correlated with all the questionnaires assessed (HADS, PVAS, PCS, and FIQ). Conclusions The Spanish version of the PSPS appears to be a valid tool in assessing mental defeat in patients with fibromyalgia. In patients with fibromyalgia and Post-Traumatic Stress Disorder (PTSD), PSPS-Spanish correlates more intensely with FIQ than in patients without PTSD. Mental defeat seems to be a psychological construct different to pain catastrophizing. PMID:21050485

The leadership team: complementary strengths or conflicting agendas?

PubMed

Miles, Stephen A; Watkins, Michael D

2007-04-01

Senior leadership teams whose members play complementary roles have been chronicled as far back as Homer's account of the Trojan War: Although King Agamemnon commanded the Greek army, Achilles, Odysseus, and Nestor each played a distinct role in defeating Troy. Today, complementary-leadership structures are common and, in some cases, even institutionalized. Think of a CEO concerned mainly with external issues and a COO who focuses internally. The authors describe four kinds of complementarity: task, expertise, cognitive, and role. The two top executives at the software company Adobe Systems, for example, represent the second kind. As CEO, Bruce Chizen draws on his sales and marketing knowledge, while COO Shantanu Narayen adds his engineering and product development expertise. Roberto Goizueta, formerly the CEO of Coca-Cola, and Douglas Ivester, his COO (who later became CEO), were famous examples of the fourth type: Goizueta, the diplomat, maintained good relations with external stakeholders; Ivester, the warrior, drove the company to defeat the competition. Bringing together two or more people with complementary strengths can compensate for the natural limitations of each. But with the benefits comes the risk of confusion, disagreement about priorities, and turf battles. Leadership succession also presents substantial challenges, especially when a COO or president who has worked in a complementary fashion with the CEO moves into the top role. An organization's board of directors and CEO can manage the risks by fostering a shared vision, common incentives, communication, and trust. They can also ensure smooth succession processes in various ways, such as brokering a gradual transfer of responsibilities or allowing the CEO and the COO to share duties as long as they maintain the logic of complementarity.

Reversing the Trend of Engineering Enrollment Declines with Innovative Outreach, Recruiting, and Retention Programs

ERIC Educational Resources Information Center

Davis, C. E.; Yeary, M. B.; Sluss, J. J., Jr.

2012-01-01

This paper discusses an all-encompassing approach to increase the number of students in engineering through innovative outreach, recruiting, and retention programs. Prior to adopting these programs, the School of Electrical and Computer Engineering (ECE) at the University of Oklahoma (OU), Norman, experienced a reduction in engineering enrollment…

Combining phage display with de novo protein sequencing for reverse engineering of monoclonal antibodies.

PubMed

Rickert, Keith W; Grinberg, Luba; Woods, Robert M; Wilson, Susan; Bowen, Michael A; Baca, Manuel

2016-01-01

The enormous diversity created by gene recombination and somatic hypermutation makes de novo protein sequencing of monoclonal antibodies a uniquely challenging problem. Modern mass spectrometry-based sequencing will rarely, if ever, provide a single unambiguous sequence for the variable domains. A more likely outcome is computation of an ensemble of highly similar sequences that can satisfy the experimental data. This outcome can result in the need for empirical testing of many candidate sequences, sometimes iteratively, to identity one which can replicate the activity of the parental antibody. Here we describe an improved approach to antibody protein sequencing by using phage display technology to generate a combinatorial library of sequences that satisfy the mass spectrometry data, and selecting for functional candidates that bind antigen. This approach was used to reverse engineer 2 commercially-obtained monoclonal antibodies against murine CD137. Proteomic data enabled us to assign the majority of the variable domain sequences, with the exception of 3-5% of the sequence located within or adjacent to complementarity-determining regions. To efficiently resolve the sequence in these regions, small phage-displayed libraries were generated and subjected to antigen binding selection. Following enrichment of antigen-binding clones, 2 clones were selected for each antibody and recombinantly expressed as antigen-binding fragments (Fabs). In both cases, the reverse-engineered Fabs exhibited identical antigen binding affinity, within error, as Fabs produced from the commercial IgGs. This combination of proteomic and protein engineering techniques provides a useful approach to simplifying the technically challenging process of reverse engineering monoclonal antibodies from protein material.

Combining phage display with de novo protein sequencing for reverse engineering of monoclonal antibodies

PubMed Central

Rickert, Keith W.; Grinberg, Luba; Woods, Robert M.; Wilson, Susan; Bowen, Michael A.; Baca, Manuel

2016-01-01

ABSTRACT The enormous diversity created by gene recombination and somatic hypermutation makes de novo protein sequencing of monoclonal antibodies a uniquely challenging problem. Modern mass spectrometry-based sequencing will rarely, if ever, provide a single unambiguous sequence for the variable domains. A more likely outcome is computation of an ensemble of highly similar sequences that can satisfy the experimental data. This outcome can result in the need for empirical testing of many candidate sequences, sometimes iteratively, to identity one which can replicate the activity of the parental antibody. Here we describe an improved approach to antibody protein sequencing by using phage display technology to generate a combinatorial library of sequences that satisfy the mass spectrometry data, and selecting for functional candidates that bind antigen. This approach was used to reverse engineer 2 commercially-obtained monoclonal antibodies against murine CD137. Proteomic data enabled us to assign the majority of the variable domain sequences, with the exception of 3–5% of the sequence located within or adjacent to complementarity-determining regions. To efficiently resolve the sequence in these regions, small phage-displayed libraries were generated and subjected to antigen binding selection. Following enrichment of antigen-binding clones, 2 clones were selected for each antibody and recombinantly expressed as antigen-binding fragments (Fabs). In both cases, the reverse-engineered Fabs exhibited identical antigen binding affinity, within error, as Fabs produced from the commercial IgGs. This combination of proteomic and protein engineering techniques provides a useful approach to simplifying the technically challenging process of reverse engineering monoclonal antibodies from protein material. PMID:26852694

Static internal performance of a single-engine onaxisymmetric-nozzle vaned-thrust-reverser design with thrust modulation capabilities

NASA Technical Reports Server (NTRS)

Leavitt, L. D.; Burley, J. R., II

1985-01-01

An investigation has been conducted at wind-off conditions in the stati-test facility of the Langley 16-Foot Transonic Tunnel. The tests were conducted on a single-engine reverser configuration with partial and full reverse-thrust modulation capabilities. The reverser design had four ports with equal areas. These ports were angled outboard 30 deg from the vertical impart of a splay angle to the reverse exhaust flow. This splaying of reverser flow was intended to prevent impingement of exhaust flow on empennage surfaces and to help avoid inlet reingestion of exhaust gas when the reverser is integrated into an actual airplane configuration. External vane boxes were located directly over each of the four ports to provide variation of reverser efflux angle from 140 deg to 26 deg (measured forward from the horizontal reference axis). The reverser model was tested with both a butterfly-type inner door and an internal slider door to provide area control for each individual port. In addition, main nozzle throat area and vector angle were varied to examine various methods of modulating thrust levels. Other model variables included vane box configuration (four or six vanes per box), orientation of external vane boxes with respect to internal port walls (splay angle shims), and vane box sideplates. Nozzle pressure ratio was varied from 2.0 approximately 7.0.

The defeat of Philip Morris' 'California Uniform Tobacco Control Act'.

PubMed Central

Macdonald, H; Aguinaga, S; Glantz, S A

1997-01-01

OBJECTIVES: This paper describes the strategies used by Philip Morris and other tobacco companies to promote a California initiative (Proposition 188) preempting local control of tobacco and those used by public health groups to defeat the initiative. METHODS: Interviews with key informants were conducted, and the written record was reviewed. RESULTS: Tobacco companies nearly succeeded in passing Proposition 188 by presenting it as a pro-health measure that would prevent children from obtaining cigarettes and provide protection against secondhand smoke. Public health groups defeated it by highlighting tobacco industry backing. A private charitable foundation also played an innovative role by financing a non-partisan public education campaign. CONCLUSIONS: Public health forces must be alert to sophisticated efforts by the tobacco industry to enact preemptive state legislation by making it look like tobacco control legislation. The coalition structure that emerged in the "No on 188" campaign represents an effective model for future tobacco control activities. The new role of charitable foundations defined in the Proposition 188 campaign can be used in other public health issues. Images FIGURE 1 PMID:9431289

Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade.

PubMed

Vasconcelos, Mailton; Stein, Dirson João; de Almeida, Rosa Maria M

2015-01-01

Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

Malignant self-regard: accounting for commonalities in vulnerably narcissistic, depressive, self-defeating, and masochistic personality disorders.

PubMed

Huprich, Steven K; Nelson, Sharon M

2014-05-01

Several personality disorders (PDs) have been of interest in the clinical literature, yet failed to have been adequately represented in the diagnostic manuals. Some of these are masochistic, self-defeating, depressive, and narcissistic PDs. The theoretical and empirical relationships among these disorders are reviewed. It is proposed that a particular type of self-structure, malignant self-regard (MSR), may account for similarities among all of them and provide a better framework upon which to understand the nature of these personality types and their discrimination from related constructs. Subsequently, a questionnaire to assess MSR was created and evaluated for its psychometric properties. The measure was found to be reliable (Cronbach's alpha=.93) and valid, given its correlations with measures of self-defeating, depressive, and vulnerably narcissistic personalities (rs range from .66 to .76). MSR also can be meaningfully differentiated from a nomological network of related constructs, including neuroticism, extraversion, depression, and grandiose narcissism. The utility of assessing self-structures, such as MSR, in the diagnostic manuals is discussed. Copyright © 2014. Published by Elsevier Inc.

Exogenous testosterone in women enhances and inhibits competitive decision-making depending on victory-defeat experience and trait dominance.

PubMed

Mehta, Pranjal H; van Son, Veerle; Welker, Keith M; Prasad, Smrithi; Sanfey, Alan G; Smidts, Ale; Roelofs, Karin

2015-10-01

The present experiment tested the causal impact of testosterone on human competitive decision-making. According to prevailing theories about testosterone's role in social behavior, testosterone should directly boost competitive decisions. But recent correlational evidence suggests that testosterone's behavioral effects may depend on specific aspects of the context and person relevant to social status (win-lose context and trait dominance). We tested the causal influence of testosterone on competitive decisions by combining hormone administration with measures of trait dominance and a newly developed social competition task in which the victory-defeat context was experimentally manipulated, in a sample of 54 female participants. Consistent with the hypothesis that testosterone has context- and person-dependent effects on competitive behavior, testosterone increased competitive decisions after victory only among high-dominant individuals but testosterone decreased competitive decisions after defeat across all participants. These results suggest that testosterone flexibly modulates competitive decision-making depending on prior social experience and dominance motivation in the service of enhancing social status. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increase in expression of brain serotonin transporter and monoamine oxidase a genes induced by repeated experience of social defeats in male mice.

PubMed

Filipenko, M L; Beilina, A G; Alekseyenko, O V; Dolgov, V V; Kudryavtseva, N N

2002-04-01

Serotonin transporter and monoamine oxidase (MAO) A are involved in the inactivation of serotonin. The former is responsible for serotonin re-uptake from the synapse, whereas the latter catalyzes serotonin deamination in presynaptic terminals. Expression of serotonin transporter and MAO A genes was investigated in raphe nuclei of midbrain of CBA/Lac male mice with repeated experience of social victories or defeats in 10 daily aggressive confrontations. The amount of cDNA of these genes was evaluated using multiplex RT-PCR. Two independent experiments revealed that the defeated mice were characterized by significantly higher levels of serotonin transporter and MAO A mRNAs than the control and aggressive animals. Increased expression of MAO A and serotonin transporter genes is suggested to reflect the accelerated serotonin degradation in response to activation of the serotonergic system functioning induced by social stress. Significant positive correlation between MAO A and serotonin transporter mRNA levels suggests common pathways of regulation of transcriptional activity of these genes.

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

PubMed Central

Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

2012-01-01

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms. PMID:22807664

DEFINING THE PLAYERS IN HIGHER-ORDER NETWORKS: PREDICTIVE MODELING FOR REVERSE ENGINEERING FUNCTIONAL INFLUENCE NETWORKS

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

McDermott, Jason E.; Costa, Michelle N.; Stevens, S.L.

A difficult problem that is currently growing rapidly due to the sharp increase in the amount of high-throughput data available for many systems is that of determining useful and informative causative influence networks. These networks can be used to predict behavior given observation of a small number of components, predict behavior at a future time point, or identify components that are critical to the functioning of the system under particular conditions. In these endeavors incorporating observations of systems from a wide variety of viewpoints can be particularly beneficial, but has often been undertaken with the objective of inferring networks thatmore » are generally applicable. The focus of the current work is to integrate both general observations and measurements taken for a particular pathology, that of ischemic stroke, to provide improved ability to produce useful predictions of systems behavior. A number of hybrid approaches have recently been proposed for network generation in which the Gene Ontology is used to filter or enrich network links inferred from gene expression data through reverse engineering methods. These approaches have been shown to improve the biological plausibility of the inferred relationships determined, but still treat knowledge-based and machine-learning inferences as incommensurable inputs. In this paper, we explore how further improvements may be achieved through a full integration of network inference insights achieved through application of the Gene Ontology and reverse engineering methods with specific reference to the construction of dynamic models of transcriptional regulatory networks. We show that integrating two approaches to network construction, one based on reverse-engineering from conditional transcriptional data, one based on reverse-engineering from in situ hybridization data, and another based on functional associations derived from Gene Ontology, using probabilities can improve results of clustering as evaluated by a predictive model of transcriptional expression levels.« less

China Naval Modernization: Implications for U.S. Navy Capabilities - Background and Issues for Congress

DTIC Science & Technology

2012-10-17

0 0 ~60 ~90 Helicopters n/a n/a n/a n/a ~34 ~153 ~157 Subtotal above aircraft n/a n/a n/a n/a ~179 ~468 ~ 505 Source: Prepared by CRS. Source for...Congressional Research Service 87 The Air-Sea Battle Concept centers on networked, integrated, attack-in-depth to disrupt, destroy and defeat ( NIA -D3) A2/AD...of U.S. forces; and defeat an adversary’s employed weapons to preserve essential U.S. Joint forces and their enablers. Through NIA -D3, air and naval

A synthetic biology approach to engineer a functional reversal of the β-oxidation cycle.

PubMed

Clomburg, James M; Vick, Jacob E; Blankschien, Matthew D; Rodríguez-Moyá, María; Gonzalez, Ramon

2012-11-16

While we have recently constructed a functional reversal of the β-oxidation cycle as a platform for the production of fuels and chemicals by engineering global regulators and eliminating native fermentative pathways, the system-level approach used makes it difficult to determine which of the many deregulated enzymes are responsible for product synthesis. This, in turn, limits efforts to fine-tune the synthesis of specific products and prevents the transfer of the engineered pathway to other organisms. In the work reported here, we overcome the aforementioned limitations by using a synthetic biology approach to construct and functionally characterize a reversal of the β-oxidation cycle. This was achieved through the in vitro kinetic characterization of each functional unit of the core and termination pathways, followed by their in vivo assembly and functional characterization. With this approach, the four functional units of the core pathway, thiolase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase, and acyl-CoA dehydrogenase/trans-enoyl-CoA reductase, were purified and kinetically characterized in vitro. When these four functional units were assembled in vivo in combination with thioesterases as the termination pathway, the synthesis of a variety of 4-C carboxylic acids from a one-turn functional reversal of the β-oxidation cycle was realized. The individual expression and modular construction of these well-defined core components exerted the majority of control over product formation, with only highly selective termination pathways resulting in shifts in product formation. Further control over product synthesis was demonstrated by overexpressing a long-chain thiolase that enables the operation of multiple turns of the reversal of the β-oxidation cycle and hence the synthesis of longer-chain carboxylic acids. The well-defined and self-contained nature of each functional unit makes the engineered reversal of the β-oxidation cycle "chassis neutral" and hence transferrable to the host of choice for efficient fuel or chemical production.

Quiet Clean Short-Haul Experimental Engine (QCSEE) Over-The-Wing (OTW) propulsion system test report. Volume 2: Aerodynamics and performance. [engine performance tests to define propulsion system performance on turbofan engines

NASA Technical Reports Server (NTRS)

1978-01-01

The design and testing of the over the wing engine, a high bypass, geared turbofan engine, are discussed. The propulsion system performance is examined for uninstalled performance and installed performance. The fan aerodynamic performance and the D nozzle and reverser thrust performance are evaluated.

The Science of Solubility: Using Reverse Engineering to Brew a Perfect Cup of Coffee

ERIC Educational Resources Information Center

West, Andrew B.; Sickel, Aaron J.; Cribbs, Jennifer D.

2015-01-01

The Next Generation Science Standards call for the integration of science and engineering. Often, the introduction of engineering activities occurs after instruction in the science content. That is, engineering is used as a way for students to elaborate on science ideas that have already been explored. However, using only this sequence of…

Forward design of a complex enzyme cascade reaction

PubMed Central

Hold, Christoph; Billerbeck, Sonja; Panke, Sven

2016-01-01

Enzymatic reaction networks are unique in that one can operate a large number of reactions under the same set of conditions concomitantly in one pot, but the nonlinear kinetics of the enzymes and the resulting system complexity have so far defeated rational design processes for the construction of such complex cascade reactions. Here we demonstrate the forward design of an in vitro 10-membered system using enzymes from highly regulated biological processes such as glycolysis. For this, we adapt the characterization of the biochemical system to the needs of classical engineering systems theory: we combine online mass spectrometry and continuous system operation to apply standard system theory input functions and to use the detailed dynamic system responses to parameterize a model of sufficient quality for forward design. This allows the facile optimization of a 10-enzyme cascade reaction for fine chemical production purposes. PMID:27677244

Mitigation of reversible self-association and viscosity in a human IgG1 monoclonal antibody by rational, structure-guided Fv engineering

PubMed Central

Geoghegan, James C.; Fleming, Ryan; Damschroder, Melissa; Bishop, Steven M.; Sathish, Hasige A.; Esfandiary, Reza

2016-01-01

ABSTRACT Undesired solution behaviors such as reversible self-association (RSA), high viscosity, and liquid-liquid phase separation can introduce substantial challenges during development of monoclonal antibody formulations. Although a global mechanistic understanding of RSA (i.e., native and reversible protein-protein interactions) is sufficient to develop robust formulation controls, its mitigation via protein engineering requires knowledge of the sites of protein-protein interactions. In the study reported here, we coupled our previous hydrogen-deuterium exchange mass spectrometry findings with structural modeling and in vitro screening to identify the residues responsible for RSA of a model IgG1 monoclonal antibody (mAb-C), and rationally engineered variants with improved solution properties (i.e., reduced RSA and viscosity). Our data show that mutation of either solvent-exposed aromatic residues within the heavy and light chain variable regions or buried residues within the heavy chain/light chain interface can significantly mitigate RSA and viscosity by reducing the IgG's surface hydrophobicity. The engineering strategy described here highlights the utility of integrating complementary experimental and in silico methods to identify mutations that can improve developability, in particular, high concentration solution properties, of candidate therapeutic antibodies. PMID:27050875

Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

PubMed

Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

2016-05-10

Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

Delta Opioid Receptor Signaling Promotes Resilience to Stress Under the Repeated Social Defeat Paradigm in Mice

PubMed Central

Henry, Mathilde S.; Bisht, Kanchan; Vernoux, Nathalie; Gendron, Louis; Torres-Berrio, Angélica; Drolet, Guy; Tremblay, Marie-Ève

2018-01-01

The adaptation to chronic stress is highly variable across individuals. Resilience to stress is a complex process recruiting various brain regions and neurotransmitter systems. The aim of this study was to investigate the involvement of endogenous opioid enkephalin (ENK) signaling in the development of stress resilience in mice. The translational model of repeated social defeat (RSD) stress was selected to mimic the unpredictable disruptions of daily life and induce resilience or vulnerability to stress. As in humans, adult C57BL/6J mice demonstrated a great variability in their response to stress under this paradigm. A social interaction (SI) test was used to discriminate between the phenotypes of resilience or vulnerability to stress. After social defeat, the expression levels of ENK mRNA and their delta opioid receptors (DOPr) were quantified in the basolateral amygdala (BLA) and BLA-target areas by in situ hybridization. In this manner, ENK mRNA levels were found to decrease in the BLA and those of DOPr in the ventral hippocampus (HPC) CA1 of vulnerable mice only. Stimulating the DOPr pathway during social defeat by pharmacological treatment with the nonpeptide, selective DOPr agonist SNC80 further induced a resilient phenotype in a majority of stressed animals, with the proportion of resilient ones increasing from 33% to 58% of the total population. Ultrastructural analyses additionally revealed a reduction of oxidative stress markers in the pyramidal cells and interneurons of the ventral HPC CA1 upon SNC80 treatment, thus proposing a mechanism by which ENK-DOPr signaling may prevent the deleterious effects of chronic social stress. PMID:29681795

Dopamine D2 receptors mediate the increase in reinstatement of the conditioned rewarding effects of cocaine induced by acute social defeat.

PubMed

Reguilón, Marina Daiana; Montagud-Romero, Sandra; Ferrer-Pérez, Carmen; Roger-Sánchez, Concepción; Aguilar, María Asunción; Miñarro, José; Rodríguez-Arias, Marta

2017-03-15

Social stress modifies the activity of brain areas involved in the rewarding effects of psychostimulants, inducing neuroadaptations in the dopaminergic mesolimbic system and modifying the sensitivity of dopamine receptors. In the present study we evaluated the effect of the dopamine D 1 - and D 2 -like receptor antagonists (SCH23390 and raclopride, respectively) on the short-time effects of acute social defeat (ASD). Male OF1 mice were socially defeated before each conditioning session of the conditioned place preference (CPP) induced by 1mg/kg or 25mg/kg of cocaine plus the corresponding dopamine antagonist. A final experiment was designed to evaluate the effect of the dopamine antagonists on the CPP induced by 3mg/kg of cocaine with or without a stress experience. Mice exposed to ASD showed an increase in reinstatement of the conditioned reinforcing effects of cocaine that was blocked by all of the dopamine receptor antagonists. Blockade of dopamine D 2 -like receptors with raclopride specifically prevented the effects of stress without affecting the rewarding properties of cocaine. However, SCH23390 inhibited cocaine-induced preference in the control groups and even induced aversion in defeated mice conditioned with the lower dose of cocaine. Moreover, the lowest dose of SCH23390 blocked the rewarding effects of 3mg/kg of cocaine-induced CPP. Our results confirm that the dopamine D 2 receptor is involved in the short-term effects of ASD on the rewarding effects of cocaine. The dopamine D 1 receptor is clearly involved in the rewarding effects of cocaine, but its role in the effects of ASD remains to be demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor

PubMed Central

Johnston, Caitlin E.; Herschel, Daniel; Lasek, Amy W.; Hammer, Ronald P.; Nikulina, Ella M.

2014-01-01

Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse. PMID:25446676

Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

PubMed

Goto, Tatsuhiko; Kubota, Yoshifumi; Toyoda, Atsushi

2016-09-01

The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P < 0.05). For comparison, the susceptible-like phenotype rates were estimated at 12.5 and 8.3% in healthy control mice fed semi-purified and non-purified diets, respectively. These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

Sex differences in behavioral and neural cross-sensitization and escalated cocaine taking as a result of episodic social defeat stress in rats

PubMed Central

Holly, Elizabeth N.; Shimamoto, Akiko; DeBold, Joseph F.; Miczek, Klaus A.

2013-01-01

RATIONALE Episodic social defeat stress results in cross-sensitization to cocaine, characterized by augmentation of locomotor activation, dopamine (DA) levels in the nucleus accumbens (NAc), and cocaine self-administration during a 24-hour “binge” in male rats. However, females are more vulnerable than males at each phase of cocaine addiction, and while these sex differences have been replicated in rats, the role of social stress in females remains largely neglected. OBJECTIVE This study examined sex and estrous cycle differences in behavioral and dopaminergic cross-sensitization to cocaine, as well as cocaine taking in an unlimited access self-administration “binge.” METHODS Long-Evans rats underwent episodic social defeat and were assessed ten days later for either (1)behavioral sensitization, as determined by locomotor activity in response to acute cocaine (10 mg/kg, ip), (2)neural sensitization, as determined by in vivo microdialysis of DA in the NAc shell in response to acute cocaine, or (3)intravenous self-administration of cocaine (0.3 mg/kg/infusion) in an unlimited access “binge.” RESULTS Social defeat stress resulted in behavioral and dopaminergic cross-sensitization in both sexes, but the effect was larger and longer lasting in stressed females. Furthermore, while stress engendered a longer “binge” in both sexes, females had a significantly longer “binge” duration than males. CONCLUSIONS These data suggest that socially stressed females exhibit a larger and longer lasting behavioral and neural cross-sensitization, as well as more dysregulated cocaine taking, than males possibly due to different alterations in the dopaminergic response in the NAc. Furthermore, estrogens appear to play a facilitatory role in both behavioral and dopaminergic sensitization. PMID:22926005

Individual differences in anhedonic and accumbal dopamine responses to chronic social stress and their link to cocaine self-administration in female rats

PubMed Central

Holly, Elizabeth N.; Boyson, Christopher O.; DeBold, Joseph F.; Miczek, Klaus A.

2014-01-01

Rationale Women are twice as likely as men to develop major depressive disorder. Exposure to chronic stress can induce depression in some vulnerable individuals, while others are resistant to depressive-like symptoms after equivalent levels of chronic stress. Objectives In female rats, individual differences in saccharin intake during chronic social defeat stress may predict subsequent cocaine self-administration, and may be attributed to alterations in mesolimbic dopamine activity. Methods Female rats were exposed to 21 days of chronic social defeat stress, during which they were evaluated for their anhedonia-like responses in the form of saccharin intake. After chronic social defeat stress, the rats were tested for behavioral cross-sensitization to cocaine and escalated cocaine self-administration in a 24-h “binge.” A separate group of animals underwent in vivo microdialysis of the nucleus accumbens (NAc) shell to assess dopamine (DA) in response to acute cocaine challenge. Results Cluster analysis revealed two phenotypes among the stressed female rats based on their saccharin intake while being exposed to stress, termed stress-resistant (SR, 28 %) and stress-sensitive (SS, 72 %). The amount of cocaine self-administered during the 24-h “binge” was positively correlated with preceding saccharin intake. The NAc DA response to a cocaine challenge was significantly lower in SR rats than in the SS and non-stressed control rats. No other significant differences were observed in behavioral cross-sensitization or cocaine self-administration prior to the “binge.” Conclusion Female rats showed individual differences in their anhedonic-like response to chronic social defeat stress, and these differences were reliably associated with subsequent cocaine-taking behavior. PMID:25178816

Cognitive and behavioural effects induced by social stress plus MDMA administration in mice.

PubMed

García-Pardo, M P; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

2017-02-15

Adverse life experiences such as social stress may make an individual more vulnerable to drug addiction and mental disorders associated with drug consumption. The present work aimed to evaluate the effects of stress induced by acute social defeat combined with the administration of 3,4-methylenedioxymethamphetamine (MDMA) on depression-like behaviour, memory function and motor response to drug in late adolescent male mice. Two groups of mice were exposed to social defeat (SD) during four encounters with an aggressive co-specific, which took place on alternate days. Immediately after defeat, animals were treated with saline or MDMA 10mg/kg (SD+SAL and SD+MDMA). In control groups, mice were placed in a neutral cage without an opponent (Control+SAL, Control+MDMA). Corticosterone levels and temperature were measured on the last day of this phase. During the following days, the behaviour of the animals was evaluated in the tail suspension test (an animal model of depression), memory tasks (passive avoidance and object recognition) and, after administration of 5mg/kg of MDMA, in the open-field test. Exposure of adult mice to acute social defeat plus MDMA increased immobility in the tail suspension test (depression-like behaviour), produced cognitive impairment, and reduced the motor response to MDMA. An increase in corticosterone levels and a decrease of temperature were also observed. As hypothesised, a combination of social stress and consumption of MDMA increases the risk of developing mental and cognitive disorders. Our results support the idea that stress is a common contributing factor to the high rate of comorbidity between substance abuse and mental disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats.

PubMed

Yee, Nicole; Plassmann, Kerstin; Fuchs, Eberhard

2011-09-01

Clinical studies have implicated adolescence as an important and vulnerable period during which traumatic experiences can predispose individuals to anxiety and mood disorders. As such, a stress model in juvenile rats (age 27-29 d) was previously developed to investigate the long-term effects of stress exposure during adolescence on behavior and physiology. This paradigm involves exposing rats to different stressors on consecutive days over a 3-day period. Here, we studied the effects of juvenile stress on long-term core body temperature regulation and acute stress-induced hyperthermia (SIH) responses using telemetry. We found no differences between control and juvenile stress rats in anxiety-related behavior on the elevated plus maze, which we attribute to stress associated with surgical implantation of telemetry devices. This highlights the severe impact of surgical stress on the results of subsequent behavioral measurements. Nonetheless, juvenile stress disrupted the circadian rhythmicity of body temperature and decreased circadian amplitude. It also induced chronic hypothermia during the dark phase of the day, when rats are most active. When subjected to acute social defeat stress as adults, juvenile stress had no impact on the SIH response relative to controls. However, 24 h later, juvenile stress rats displayed an elevated SIH response in anticipation of social defeat when re-exposed to the social defeat environment. Taken together, our findings indicate that juvenile stress can induce long-term alterations in body temperature regulation and heighten the increase in temperature associated with anticipation of social defeat. The outcomes of behavioral measurements in these experiments, however, are severely affected by surgical stress. Copyright © 2011 Elsevier Inc. All rights reserved.

The long-term effects of stress and kappa opioid receptor activation on conditioned place aversion in male and female California mice.

PubMed

Laman-Maharg, Abigail R; Copeland, Tiffany; Sanchez, Evelyn Ordoñes; Campi, Katharine L; Trainor, Brian C

2017-08-14

Psychosocial stress leads to the activation of kappa opioid receptors (KORs), which induce dysphoria and facilitate depression-like behaviors. However, less is known about the long-term effects of stress and KORs in females. We examined the long-term effects of social defeat stress on the aversive properties of KOR activation in male and female California mice (Peromyscus californicus) using a conditioned place aversion paradigm. Female California mice naïve to social defeat, formed a place aversion following treatment with 2.5mg/kg of the KOR agonist U50,488, but females exposed to defeat did not form a place aversion to this dose. This supports the finding by others that social defeat weakens the aversive properties of KOR agonists. In contrast, both control and stressed males formed an aversion to 10mg/kg of U50,488. We also examined EGR1 immunoreactivity, an indirect marker of neuronal activity, in the nucleus accumbens (NAc) and found that stress and treatment with 10mg/kg of U50,488 increased EGR1 immunoreactivity in the NAc core in females but reduced activation in males. The effects of stress and U50,488 on EGR1 were specific to the NAc, as we found no differences in the bed nucleus of the stria terminalis. In summary, our data indicate important sex differences in the long-term effects of stress and indicate the need for further study of the molecular mechanisms mediating the behavioral effects of KOR in both males and females. Copyright © 2017 Elsevier B.V. All rights reserved.

Re-establishment of Anxiety in Stress-Sensitized Mice Is Caused by Monocyte Trafficking from the Spleen to the Brain

PubMed Central

Wohleb, Eric S.; McKim, Daniel B.; Shea, Daniel T.; Powell, Nicole D.; Tarr, Andrew J.; Sheridan, John F.; Godbout, Jonathan P.

2014-01-01

Background Persistent anxiety-like symptoms may have an inflammatory-related pathophysiology. Our previous work using repeated social defeat (RSD) in mice showed that recruitment of peripheral myeloid cells to the brain is required for the development of anxiety. Here, we aimed to determine if 1) RSD promotes prolonged anxiety through redistribution of myeloid cells and 2) prior exposure to RSD sensitizes the neuroimmune axis to secondary subthreshold stress. Methods Mice were subjected to RSD and several immune and behavioral parameters were determined 0.5, 8, or 24 days later. In follow-up studies, control and RSD mice were subjected to subthreshold stress at 24 days. Results Repeated social defeat-induced macrophage recruitment to the brain corresponded with development and maintenance of anxiety-like behavior 8 days after RSD, but neither remained at 24 days. Nonetheless, social avoidance and an elevated neuroinflammatory profile were maintained at 24 days. Subthreshold social defeat in RSD-sensitized mice increased peripheral macrophage trafficking to the brain that promoted re-establishment of anxiety. Moreover, subthreshold social defeat increased social avoidance in RSD-sensitized mice compared with naïve mice. Stress-induced monocyte trafficking was linked to redistribution of myeloid progenitor cells in the spleen. Splenectomy before subthreshold stress attenuated macrophage recruitment to the brain and prevented anxiety-like behavior in RSD-sensitized mice. Conclusions These data indicate that monocyte trafficking from the spleen to the brain contributes re-establishment of anxiety in stress-sensitized mice. These findings show that neuroinflammatory mechanisms promote mood disturbances following stress-sensitization and outline novel neuroimmune interactions that underlie recurring anxiety disorders such as posttraumatic stress disorder. PMID:24439304

Re-establishment of anxiety in stress-sensitized mice is caused by monocyte trafficking from the spleen to the brain.

PubMed

Wohleb, Eric S; McKim, Daniel B; Shea, Daniel T; Powell, Nicole D; Tarr, Andrew J; Sheridan, John F; Godbout, Jonathan P

2014-06-15

Persistent anxiety-like symptoms may have an inflammatory-related pathophysiology. Our previous work using repeated social defeat (RSD) in mice showed that recruitment of peripheral myeloid cells to the brain is required for the development of anxiety. Here, we aimed to determine if 1) RSD promotes prolonged anxiety through redistribution of myeloid cells and 2) prior exposure to RSD sensitizes the neuroimmune axis to secondary subthreshold stress. Mice were subjected to RSD and several immune and behavioral parameters were determined .5, 8, or 24 days later. In follow-up studies, control and RSD mice were subjected to subthreshold stress at 24 days. Repeated social defeat-induced macrophage recruitment to the brain corresponded with development and maintenance of anxiety-like behavior 8 days after RSD, but neither remained at 24 days. Nonetheless, social avoidance and an elevated neuroinflammatory profile were maintained at 24 days. Subthreshold social defeat in RSD-sensitized mice increased peripheral macrophage trafficking to the brain that promoted re-establishment of anxiety. Moreover, subthreshold social defeat increased social avoidance in RSD-sensitized mice compared with naïve mice. Stress-induced monocyte trafficking was linked to redistribution of myeloid progenitor cells in the spleen. Splenectomy before subthreshold stress attenuated macrophage recruitment to the brain and prevented anxiety-like behavior in RSD-sensitized mice. These data indicate that monocyte trafficking from the spleen to the brain contributes re-establishment of anxiety in stress-sensitized mice. These findings show that neuroinflammatory mechanisms promote mood disturbances following stress-sensitization and outline novel neuroimmune interactions that underlie recurring anxiety disorders such as posttraumatic stress disorder. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Prosocial effects of prolactin in male rats: Social recognition, social approach and social learning.

PubMed

Donhoffner, Mary E; Al Saleh, Samar; Schink, Olivia; Wood, Ruth I

2017-11-01

Prolactin (PRL) and oxytocin (OT) are pituitary hormones essential for lactation, but also promote sexual behavior. OT stimulates social behaviors, such as recognition, approach, and learning, but less is known about PRL in these behaviors. Since PRL and OT have complementary functions in reproduction, we hypothesized that PRL increases social recognition, approach, and learning. Male Long-Evans rats received ovine PRL (oPRL; 0.5, 2.0 or 5.0mg/kg), the PRL antagonist bromocriptine (0.1, 3.0 or 5.0mg/kg) or saline 20 mins before testing for recognition of familiar vs. unfamiliar stimulus males. Saline controls preferred the unfamiliar male (p<0.05), while bromocriptine blocked this preference. oPRL did not increase preference. To measure social approach, we determined if PRL restores approach 2h after defeat by an aggressive male. Defeated rats avoided the aggressive male. 2mg/kg oPRL, before or after defeat, restored approach towards the aggressive male (p<0.05). In non-defeated rats, oPRL or 3mg/kg bromocriptine had no effect. To determine if PRL increases social learning, we tested social transmission of food preference. Rats choose between two unfamiliar flavors, one of which they have previously been exposed to through interaction with a demonstrator rat. Vehicle controls preferred chow with the demonstrated flavor over the novel flavor. oPRL-treated rats were similar. Bromocriptine-treated rats failed to show a preference. When tested one week later, only oPRL-treated rats preferred the demonstrated flavor. The results suggest that PRL is required for social recognition and learning, and that increasing PRL enhances social memory and approach, similar to OT. Copyright © 2017 Elsevier Inc. All rights reserved.

Project-Based Teaching-Learning Computer-Aided Engineering Tools

ERIC Educational Resources Information Center

Simoes, J. A.; Relvas, C.; Moreira, R.

2004-01-01

Computer-aided design, computer-aided manufacturing, computer-aided analysis, reverse engineering and rapid prototyping are tools that play an important key role within product design. These are areas of technical knowledge that must be part of engineering and industrial design courses' curricula. This paper describes our teaching experience of…

More than Just Hot Air: How Hairdryers and Role Models Inspire Girls in Engineering

ERIC Educational Resources Information Center

Kekelis, Linda; Larkin, Molly; Gomes, Lyn

2014-01-01

This article describes a reverse-engineering project where female students take a part a hair dryer--giving them an opportunity to see the many different kinds of engineering disciplines involved in making a hairdryer and that they work together. Mechanical Engineer, Lyn Gome, describes her experience leading a group of middle school girls through…

Profile of an Effective Engineering Manager at the Naval Avionics Center

DTIC Science & Technology

1991-06-01

GROUP Leadership ; Engineering Management Effectiveness; Engineers; Engineering Managers ; Naval Avionics Center 19 ABSTR. T (Continue on reverse if...Personnel. The purpose of the Institute is to support the implementation of the NAC Leadership / Management Principles throughout NAC. The Leadership ... Management Principles are as follows: - Develc 2 and Maintain a Corporate Outlook. - Communicate the Organizational Vision through Positive Leadership

Analysis of the flow field generated near an aircraft engine operating in reverse thrust. M.S. Thesis

NASA Technical Reports Server (NTRS)

Ledwith, W. A., Jr.

1972-01-01

A computer solution is developed to the exhaust gas reingestion problem for aircraft operating in the reverse thrust mode on a crosswind-free runway. The computer program determines the location of the inlet flow pattern, whether the exhaust efflux lies within the inlet flow pattern or not, and if so, the approximate time before the reversed flow reaches the engine inlet. The program is written so that the user is free to select discrete runway speeds or to study the entire aircraft deceleration process for both the far field and cross-ingestion problems. While developed with STOL applications in mind, the solution is equally applicable to conventional designs. The inlet and reversed jet flow fields involved in the problem are assumed to be noninteracting. The nacelle model used in determining the inlet flow field is generated using an iterative solution to the Neuman problem from potential flow theory while the reversed jet flow field is adapted using an empirical correlation from the literature. Sample results obtained using the program are included.

Combustion Light Gas Gun Technology Demonstration

DTIC Science & Technology

2007-01-23

J. G. Handbook of Cryogenic Engineering. Philadelphia: Taylor and Francis, 1998. ISBN 1-56032-332-9 Myth #2 from “Twenty Hydrogen Myths” by...the second using Helium-refrigerated reverse Brayton cycle manufactured by Linde. Neither system was designed specifically for naval applications...8 Since floor space is of a premium, the helium refrigerated reverse Brayton cycle is the system of primary current interest. The reverse Brayton

Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster.

PubMed

Trannoy, Séverine; Penn, Jill; Lucey, Kenia; Popovic, David; Kravitz, Edward A

2016-04-26

In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters.

A standardized protocol for repeated social defeat stress in mice

PubMed Central

Golden, Sam A; Covington, Herbert E; Berton, Olivier; Russo, Scott J

2011-01-01

A major impediment to novel drug development has been the paucity of animal models that accurately reflect symptoms of affective disorders. In animal models, prolonged social stress has proven to be useful in understanding the molecular mechanisms underlying affective-like disorders. When considering experimental approaches for studying depression, social defeat stress, in particular, has been shown to have excellent etiological, predictive, discriminative and face validity. Described here is a protocol whereby C57BL/6J mice that are repeatedly subjected to bouts of social defeat by a larger and aggressive CD-1 mouse results in the development of a clear depressive-like syndrome, characterized by enduring deficits in social interactions. Specifically, the protocol consists of three important stages, beginning with the selection of aggressive CD-1 mice, followed by agonistic social confrontations between the CD-1 and C57BL/6J mice, and concluding with the confirmation of social avoidance in subordinate C57BL/6J mice. The automated detection of social avoidance allows a marked increase in throughput, reproducibility and quantitative analysis. This protocol is highly adaptable, but in its most common form it requires 3–4 weeks for completion. PMID:21799487

[Serotonergic genes in the development of anxiety/depression-like state and pathology of aggressive behavior in male mice: RNA-seq data].

PubMed

Kudryavtseva, N N; Smagin, D A; Kovalenko, I L; Galyamina, A G; Vishnivetskaya, G B; Babenko, V N; Orlov, Yu L

2017-01-01

In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice. In mice of both groups, the Tph2, Ddc, Slc6a4, Htr2a, Htr3a, Htr5b, Slc18a2, and Bdnf genes were downregulated in the MRN and the Tph2, Ddc, and Slc6a4 genes were upregulated in the VTA. These changes were more significant in defeated mice. The Htr5b gene has first been shown to be involved in mechanisms of depression and pathology of aggressive behavior. In the defeated mice, the expression levels of the Htr4 and Aldh1b1 genes were increased in the MRN, and expression levels of the Maob, Htr4, Htr1a, and Slc18a2 genes were increased in the VTA, while the expression level of the Htr3a gene was decreased. In the HYP of aggressive mice the Maoa, Htr2a, Htr2c, and Creb1 genes were downregulated and the Htr6 gene was upregulated. In the defeated mice, the Maoa and Creb1 genes were downregulated and the Htr6 and Aldh1b1 genes were upregulated in the HYP. In the STR, the Htr1a gene was downregulated and the Htr7 and Bdnf genes were upregulated. The Htr1b gene was upregulated in the HIP. The coexpression of dopaminergic and serotonergic genes in the MRN and VTA in the control of pathological behaviors is discussed. Thus, the complex pattern of differential expression of serotonergic genes in brain regions developing under repeated agonistic interactions in mice in dependence on behavioral pathology have been observed.

Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data

PubMed Central

Liu, Zhi-Ping

2015-01-01

Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented. PMID:25937810

Variable neighborhood search for reverse engineering of gene regulatory networks.

PubMed

Nicholson, Charles; Goodwin, Leslie; Clark, Corey

2017-01-01

A new search heuristic, Divided Neighborhood Exploration Search, designed to be used with inference algorithms such as Bayesian networks to improve on the reverse engineering of gene regulatory networks is presented. The approach systematically moves through the search space to find topologies representative of gene regulatory networks that are more likely to explain microarray data. In empirical testing it is demonstrated that the novel method is superior to the widely employed greedy search techniques in both the quality of the inferred networks and computational time. Copyright © 2016 Elsevier Inc. All rights reserved.

GRASP/Ada: Graphical Representations of Algorithms, Structures, and Processes for Ada. The development of a program analysis environment for Ada: Reverse engineering tools for Ada, task 2, phase 3

NASA Technical Reports Server (NTRS)

Cross, James H., II

1991-01-01

The main objective is the investigation, formulation, and generation of graphical representations of algorithms, structures, and processes for Ada (GRASP/Ada). The presented task, in which various graphical representations that can be extracted or generated from source code are described and categorized, is focused on reverse engineering. The following subject areas are covered: the system model; control structure diagram generator; object oriented design diagram generator; user interface; and the GRASP library.

Effects of an in-flight thrust reverser on the stability and control characteristics of a single-engine fighter airplane model

NASA Technical Reports Server (NTRS)

Mercer, C. E.; Maiden, D. L.

1972-01-01

The changes in thrust minus drag performance as well as longitudinal and directional stability and control characteristics of a single-engine jet aircraft attributable to an in-flight thrust reverser of the blocker-deflector door type were investigated in a 16-foot transonic wind tunnel. The longitudinal and directional stability data are presented. Test conditions simulated landing approach conditions as well as high speed maneuvering such as may be required for combat or steep descent from high altitude.

Development of high temperature liquid lubricants for low-heat rejection: Heavy duty diesel engines

NASA Technical Reports Server (NTRS)

Wiczynski, P. D.; Marolewski, T. A.

1993-01-01

The objective of this DOE program was to develop a liquid lubricant that will allow advanced diesel engines to operate at top ring reversal temperatures approaching 500 C and sump temperatures approaching 250 C. The lubricants developed demonstrated at marginal increase in sump temperature capability, approximately 15 C, and an increase in top ring reversal temperature. A 15W-40 synthetic lubricant designated HTL-4 was the best lubricant developed in terms of stability, wear control, deposit control dispersancy, and particulate emissions.

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

PubMed

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

Software engineering

NASA Technical Reports Server (NTRS)

Fridge, Ernest M., III; Hiott, Jim; Golej, Jim; Plumb, Allan

1993-01-01

Today's software systems generally use obsolete technology, are not integrated properly with other software systems, and are difficult and costly to maintain. The discipline of reverse engineering is becoming prominent as organizations try to move their systems up to more modern and maintainable technology in a cost effective manner. The Johnson Space Center (JSC) created a significant set of tools to develop and maintain FORTRAN and C code during development of the space shuttle. This tool set forms the basis for an integrated environment to reengineer existing code into modern software engineering structures which are then easier and less costly to maintain and which allow a fairly straightforward translation into other target languages. The environment will support these structures and practices even in areas where the language definition and compilers do not enforce good software engineering. The knowledge and data captured using the reverse engineering tools is passed to standard forward engineering tools to redesign or perform major upgrades to software systems in a much more cost effective manner than using older technologies. The latest release of the environment was in Feb. 1992.

Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering

PubMed Central

Wang, Huiyuan

2015-01-01

Adaptable hydrogels have recently emerged as a promising platform for three-dimensional (3D) cell encapsulation and culture. In conventional, covalently crosslinked hydrogels, degradation is typically required to allow complex cellular functions to occur, leading to bulk material degradation. In contrast, adaptable hydrogels are formed by reversible crosslinks. Through breaking and re-forming of the reversible linkages, adaptable hydrogels can be locally modified to permit complex cellular functions while maintaining their long-term integrity. In addition, these adaptable materials can have biomimetic viscoelastic properties that make them well suited for several biotechnology and medical applications. In this review, adaptable hydrogel design considerations and linkage selections are overviewed, with a focus on various cell compatible crosslinking mechanisms that can be exploited to form adaptable hydrogels for tissue engineering. PMID:25989348

In-line stirling energy system

DOEpatents

Backhaus, Scott N [Espanola, NM; Keolian, Robert [State College, PA

2011-03-22

A high efficiency generator is provided using a Stirling engine to amplify an acoustic wave by heating the gas in the engine in a forward mode. The engine is coupled to an alternator to convert heat input to the engine into electricity. A plurality of the engines and respective alternators can be coupled to operate in a timed sequence to produce multi-phase electricity without the need for conversion. The engine system may be operated in a reverse mode as a refrigerator/heat pump.

Software reengineering

NASA Technical Reports Server (NTRS)

Fridge, Ernest M., III

1991-01-01

Today's software systems generally use obsolete technology, are not integrated properly with other software systems, and are difficult and costly to maintain. The discipline of reverse engineering is becoming prominent as organizations try to move their systems up to more modern and maintainable technology in a cost effective manner. JSC created a significant set of tools to develop and maintain FORTRAN and C code during development of the Space Shuttle. This tool set forms the basis for an integrated environment to re-engineer existing code into modern software engineering structures which are then easier and less costly to maintain and which allow a fairly straightforward translation into other target languages. The environment will support these structures and practices even in areas where the language definition and compilers do not enforce good software engineering. The knowledge and data captured using the reverse engineering tools is passed to standard forward engineering tools to redesign or perform major upgrades to software systems in a much more cost effective manner than using older technologies. A beta vision of the environment was released in Mar. 1991. The commercial potential for such re-engineering tools is very great. CASE TRENDS magazine reported it to be the primary concern of over four hundred of the top MIS executives.

Critical evaluation of reverse engineering tool Imagix 4D!

PubMed

Yadav, Rashmi; Patel, Ravindra; Kothari, Abhay

2016-01-01

The comprehension of legacy codes is difficult to understand. Various commercial reengineering tools are available that have unique working styles, and are equipped with their inherent capabilities and shortcomings. The focus of the available tools is in visualizing static behavior not the dynamic one. Therefore, it is difficult for people who work in software product maintenance, code understanding reengineering/reverse engineering. Consequently, the need for a comprehensive reengineering/reverse engineering tool arises. We found the usage of Imagix 4D to be good as it generates the maximum pictorial representations in the form of flow charts, flow graphs, class diagrams, metrics and, to a partial extent, dynamic visualizations. We evaluated Imagix 4D with the help of a case study involving a few samples of source code. The behavior of the tool was analyzed on multiple small codes and a large code gcc C parser. Large code evaluation was performed to uncover dead code, unstructured code, and the effect of not including required files at preprocessing level. The utility of Imagix 4D to prepare decision density and complexity metrics for a large code was found to be useful in getting to know how much reengineering is required. At the outset, Imagix 4D offered limitations in dynamic visualizations, flow chart separation (large code) and parsing loops. The outcome of evaluation will eventually help in upgrading Imagix 4D and posed a need of full featured tools in the area of software reengineering/reverse engineering. It will also help the research community, especially those who are interested in the realm of software reengineering tool building.

A shape-based inter-layer contours correspondence method for ICT-based reverse engineering

PubMed Central

Duan, Liming; Yang, Shangpeng; Zhang, Gui; Feng, Fei; Gu, Minghui

2017-01-01

The correspondence of a stack of planar contours in ICT (industrial computed tomography)-based reverse engineering, a key step in surface reconstruction, is difficult when the contours or topology of the object are complex. Given the regularity of industrial parts and similarity of the inter-layer contours, a specialized shape-based inter-layer contours correspondence method for ICT-based reverse engineering was presented to solve the above problem based on the vectorized contours. In this paper, the vectorized contours extracted from the slices consist of three graphical primitives: circles, arcs and segments. First, the correspondence of the inter-layer primitives is conducted based on the characteristics of the primitives. Second, based on the corresponded primitives, the inter-layer contours correspond with each other using the proximity rules and exhaustive search. The proposed method can make full use of the shape information to handle industrial parts with complex structures. The feasibility and superiority of this method have been demonstrated via the related experiments. This method can play an instructive role in practice and provide a reference for the related research. PMID:28489867

A shape-based inter-layer contours correspondence method for ICT-based reverse engineering.

PubMed

Duan, Liming; Yang, Shangpeng; Zhang, Gui; Feng, Fei; Gu, Minghui

2017-01-01

The correspondence of a stack of planar contours in ICT (industrial computed tomography)-based reverse engineering, a key step in surface reconstruction, is difficult when the contours or topology of the object are complex. Given the regularity of industrial parts and similarity of the inter-layer contours, a specialized shape-based inter-layer contours correspondence method for ICT-based reverse engineering was presented to solve the above problem based on the vectorized contours. In this paper, the vectorized contours extracted from the slices consist of three graphical primitives: circles, arcs and segments. First, the correspondence of the inter-layer primitives is conducted based on the characteristics of the primitives. Second, based on the corresponded primitives, the inter-layer contours correspond with each other using the proximity rules and exhaustive search. The proposed method can make full use of the shape information to handle industrial parts with complex structures. The feasibility and superiority of this method have been demonstrated via the related experiments. This method can play an instructive role in practice and provide a reference for the related research.

MORE: mixed optimization for reverse engineering--an application to modeling biological networks response via sparse systems of nonlinear differential equations.

PubMed

Sambo, Francesco; de Oca, Marco A Montes; Di Camillo, Barbara; Toffolo, Gianna; Stützle, Thomas

2012-01-01

Reverse engineering is the problem of inferring the structure of a network of interactions between biological variables from a set of observations. In this paper, we propose an optimization algorithm, called MORE, for the reverse engineering of biological networks from time series data. The model inferred by MORE is a sparse system of nonlinear differential equations, complex enough to realistically describe the dynamics of a biological system. MORE tackles separately the discrete component of the problem, the determination of the biological network topology, and the continuous component of the problem, the strength of the interactions. This approach allows us both to enforce system sparsity, by globally constraining the number of edges, and to integrate a priori information about the structure of the underlying interaction network. Experimental results on simulated and real-world networks show that the mixed discrete/continuous optimization approach of MORE significantly outperforms standard continuous optimization and that MORE is competitive with the state of the art in terms of accuracy of the inferred networks.

Where Are All the Women Engineers? An Insider's View of Socialization and Power in Engineering Education

ERIC Educational Resources Information Center

Christman, Jeanne

2017-01-01

Despite more than thirty years of the underrepresentation of women in engineering being a persistent concern, research on the cause of the problem has not been successful in reversing the trend. A plethora of theories as to why females are not entering engineering exist, yet they only address issues on the surface and do not attend to a…

Natural tooth intrusion and reversal in implant-assisted prosthesis: evidence of and a hypothesis for the occurrence.

PubMed

Sheets, C G; Earthmann, J C

1993-12-01

Based on clinical observation, a hypothesis of the mechanism of intrusion of natural teeth in an implant-assisted prosthesis is suggested. Engineering principles are presented that establish an energy absorption model as it relates to the implant-assisted prosthesis. In addition, in the course of patient treatment it has been discovered that the intrusion of natural teeth can be reversed. Patient histories that demonstrate intrusion reversal are reviewed. The possible mechanisms for the intrusion/reversal phenomenon are presented and preventative recommendations are given.

Low heat transfer, high strength window materials

DOEpatents

Berlad, Abraham L.; Salzano, Francis J.; Batey, John E.

1978-01-01

A multi-pane window with improved insulating qualities; comprising a plurality of transparent or translucent panes held in an essentially parallel, spaced-apart relationship by a frame. Between at least one pair of panes is a convection defeating means comprising an array of parallel slats or cells so designed as to prevent convection currents from developing in the space between the two panes. The convection defeating structures may have reflective surfaces so as to improve the collection and transmittance of the incident radiant energy. These same means may be used to control (increase or decrease) the transmittance of solar energy as well as to decouple the radiative transfer between the interior surfaces of the transparent panes.

The blossoms of loss: Ovid's floral metamorphoses and Poussin's realm of flora.

PubMed

Tutter, Adele

2014-07-01

Alluring and fertile, the flower connotes a locus of desire. The floral metamorphic myths narrated in Ovid's Metamorphoses (AD 8a) thematize the price of desire--the shame, grief, and rage of rejection and rivalrous defeat--and symbolize the generative transformation that frustrated desire and competitive loss can promote. In the deceptively beautiful painting Realm of Flora of 1631, Nicolas Poussin enlists these myths as allegories of his own great creative leap, an aesthetic metamorphosis that followed shattering defeats. Extending the association between creativity and object loss to competitive loss, Poussin holds a mirror to our powerful drive to prevail and create anew from the ashes of loss. © 2014 The Psychoanalytic Quarterly, Inc.

Thermoelectric energy converters under a trade-off figure of merit with broken time-reversal symmetry

NASA Astrophysics Data System (ADS)

Iyyappan, I.; Ponmurugan, M.

2017-09-01

We study the performance of a three-terminal thermoelectric device such as heat engine and refrigerator with broken time-reversal symmetry by applying the unified trade-off figure of merit (\\dotΩ criterion) which accounts for both useful energy and losses. For the heat engine, we find that a thermoelectric device working under the maximum \\dotΩ criterion gives a significantly better performance than a device working at maximum power output. Within the framework of linear irreversible thermodynamics such a direct comparison is not possible for refrigerators, however, our study indicates that, for refrigerator, the maximum cooling load gives a better performance than the maximum \\dotΩ criterion for a larger asymmetry. Our results can be useful to choose a suitable optimization criterion for operating a real thermoelectric device with broken time-reversal symmetry.

Thrust reverser design studies for an over-the-wing STOL transport

NASA Technical Reports Server (NTRS)

Ammer, R. C.; Sowers, H. D.

1977-01-01

Aerodynamic and acoustics analytical studies were conducted to evaluate three thrust reverser designs for potential use on commercial over-the-wing STOL transports. The concepts were: (1) integral D nozzle/target reverser, (2) integral D nozzle/top arc cascade reverser, and (3) post exit target reverser integral with wing. Aerodynamic flowpaths and kinematic arrangements for each concept were established to provide a 50% thrust reversal capability. Analytical aircraft stopping distance/noise trade studies conducted concurrently with flow path design showed that these high efficiency reverser concepts are employed at substantially reduced power settings to meet noise goals of 100 PNdB on a 152.4 m sideline and still meet 609.6 m landing runway length requirements. From an overall installation standpoint, only the integral D nozzle/target reverser concept was found to penalize nacelle cruise performance; for this concept a larger nacelle diameter was required to match engine cycle effective area demand in reverse thrust.

Quiet Clean Short-haul Experimental Engine (QCSEE) Under-The-Wing (UTW) engine composite nacelle test report. Volume 1: Summary, aerodynamic and mechanical performance

NASA Technical Reports Server (NTRS)

1979-01-01

The performance test results of the final under-the-wing engine configuration are presented. One hundred and six hours of engine operation were completed, including mechanical and performance checkout, baseline acoustic testing with a bellmouth inlet, reverse thrust testing, acoustic technology tests, and limited controls testing. The engine includes a variable pitch fan having advanced composite fan blades and using a ball-spline pitch actuation system.

Reverse engineering biological networks :applications in immune responses to bio-toxins.

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

Martino, Anthony A.; Sinclair, Michael B.; Davidson, George S.

Our aim is to determine the network of events, or the regulatory network, that defines an immune response to a bio-toxin. As a model system, we are studying T cell regulatory network triggered through tyrosine kinase receptor activation using a combination of pathway stimulation and time-series microarray experiments. Our approach is composed of five steps (1) microarray experiments and data error analysis, (2) data clustering, (3) data smoothing and discretization, (4) network reverse engineering, and (5) network dynamics analysis and fingerprint identification. The technological outcome of this study is a suite of experimental protocols and computational tools that reverse engineermore » regulatory networks provided gene expression data. The practical biological outcome of this work is an immune response fingerprint in terms of gene expression levels. Inferring regulatory networks from microarray data is a new field of investigation that is no more than five years old. To the best of our knowledge, this work is the first attempt that integrates experiments, error analyses, data clustering, inference, and network analysis to solve a practical problem. Our systematic approach of counting, enumeration, and sampling networks matching experimental data is new to the field of network reverse engineering. The resulting mathematical analyses and computational tools lead to new results on their own and should be useful to others who analyze and infer networks.« less

Psychological Processes and Repeat Suicidal Behavior: A Four-Year Prospective Study

PubMed Central

2013-01-01

Objective: Although suicidal behavior is a major public health concern, understanding of individually sensitive suicide risk mechanisms is limited. In this study, the authors investigated, for the first time, the utility of defeat and entrapment in predicting repeat suicidal behavior in a sample of suicide attempters. Method: Seventy patients hospitalized after a suicide attempt completed a range of clinical and psychological measures (depression, hopelessness, suicidal ideation, defeat, and entrapment) while in hospital. Four years later, a nationally linked database was used to determine who had been hospitalized again after a suicide attempt. Results: Over 4 years, 24.6% of linked participants were readmitted to hospital after a suicidal attempt. In univariate logistic regression analyses, defeat and entrapment as well as depression, hopelessness, past suicide attempts, and suicidal ideation all predicted suicidal behavior over this interval. However, in the multivariate analysis, entrapment and past frequency of suicide attempts were the only significant predictors of suicidal behavior. Conclusions: This longitudinal study supports the utility of a new theoretical model in the prediction of suicidal behavior. Individually sensitive suicide risk processes like entrapment could usefully be targeted in treatment interventions to reduce the risk of repeat suicidal behavior in those who have been previously hospitalized after a suicide attempt. PMID:23855989

A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

PubMed Central

Goto, Tatsuhiko; Toyoda, Atsushi

2015-01-01

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of depression is essential. Because there are several types of depression, various animal models are needed for a deeper understanding of the disorder. Previously, a mouse model of subchronic and mild social defeat stress (sCSDS) using a modified chronic social defeat stress (CSDS) paradigm was established. In the paradigm, to reduce physical injuries from aggressors, the duration of physical contact between the aggressor and a subordinate was reduced compared to in the original CSDS paradigm. sCSDS mice showed increased body weight gain, food intake, and water intake during the stress period, and their social behaviors were suppressed after the stress period. In terms of the face validity of the stress-induced overeating and overdrinking following the increased body weight gain, the sCSDS mice may show some features related to atypical depression in humans. Thus, a mouse model of sCSDS may be useful for studying the pathogenic mechanisms underlying depression. This protocol will help establish the sCSDS mouse model, especially for studying the mechanisms underlying stress-induced weight gain and polydipsia- and hyperphagia-like symptoms. PMID:26650680

System Re-engineering Project Executive Summary

DTIC Science & Technology

1991-11-01

Management Information System (STAMIS) application. This project involved reverse engineering, evaluation of structured design and object-oriented design, and re- implementation of the system in Ada. This executive summary presents the approach to re-engineering the system, the lessons learned while going through the process, and issues to be considered in future tasks of this nature.... Computer-Aided Software Engineering (CASE), Distributed Software, Ada, COBOL, Systems Analysis, Systems Design, Life Cycle Development, Functional Decomposition, Object-Oriented

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

PubMed

Kamal, Amer; Van der Harst, Johanneke E; Kapteijn, Chantal M; Baars, Annemarie J M; Spruijt, Berry M; Ramakers, Geert M J

2010-04-01

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice.

PubMed

Zhang, Qi; Guo, Fei; Fu, Zhi-wen; Zhang, Bing; Huang, Cheng-gang; Li, Yang

2016-02-01

N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg·kg(-1)·d(-1)) or a positive-control drug, fluoxetine (10 mg·kg(-1)·d(-1)) for 3 weeks. Behavioral assessments were carried out every week. In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC50 value of 2.8 μmol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltage-dependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression.

Gender Differences in the Consistency of Middle School Students' Interest in Engineering and Science Careers

ERIC Educational Resources Information Center

Ing, Marsha; Aschbacher, Pamela R.; Tsai, Sherry M.

2014-01-01

This longitudinal study analyzes survey responses in seventh, eighth, and ninth grade from diverse public school students (n = 482) to explore gender differences in engineering and science career preferences. Females were far more likely to express interest in a science career (31%) than an engineering career (13%), while the reverse was true for…

Reverse Engineering and Software Products Reuse to Teach Collaborative Web Portals: A Case Study with Final-Year Computer Science Students

ERIC Educational Resources Information Center

Medina-Dominguez, Fuensanta; Sanchez-Segura, Maria-Isabel; Mora-Soto, Arturo; Amescua, Antonio

2010-01-01

The development of collaborative Web applications does not follow a software engineering methodology. This is because when university students study Web applications in general, and collaborative Web portals in particular, they are not being trained in the use of software engineering techniques to develop collaborative Web portals. This paper…

Computational discovery and in vivo validation of hnf4 as a regulatory gene in planarian regeneration.

PubMed

Lobo, Daniel; Morokuma, Junji; Levin, Michael

2016-09-01

Automated computational methods can infer dynamic regulatory network models directly from temporal and spatial experimental data, such as genetic perturbations and their resultant morphologies. Recently, a computational method was able to reverse-engineer the first mechanistic model of planarian regeneration that can recapitulate the main anterior-posterior patterning experiments published in the literature. Validating this comprehensive regulatory model via novel experiments that had not yet been performed would add in our understanding of the remarkable regeneration capacity of planarian worms and demonstrate the power of this automated methodology. Using the Michigan Molecular Interactions and STRING databases and the MoCha software tool, we characterized as hnf4 an unknown regulatory gene predicted to exist by the reverse-engineered dynamic model of planarian regeneration. Then, we used the dynamic model to predict the morphological outcomes under different single and multiple knock-downs (RNA interference) of hnf4 and its predicted gene pathway interactors β-catenin and hh Interestingly, the model predicted that RNAi of hnf4 would rescue the abnormal regenerated phenotype (tailless) of RNAi of hh in amputated trunk fragments. Finally, we validated these predictions in vivo by performing the same surgical and genetic experiments with planarian worms, obtaining the same phenotypic outcomes predicted by the reverse-engineered model. These results suggest that hnf4 is a regulatory gene in planarian regeneration, validate the computational predictions of the reverse-engineered dynamic model, and demonstrate the automated methodology for the discovery of novel genes, pathways and experimental phenotypes. michael.levin@tufts.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress.

PubMed

Hanke, M L; Powell, N D; Stiner, L M; Bailey, M T; Sheridan, J F

2012-10-01

During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation. Copyright © 2012 Elsevier Inc. All rights reserved.

Generation of recombinant rotaviruses expressing fluorescent proteins using an optimized reverse genetics system.

PubMed

Komoto, Satoshi; Fukuda, Saori; Ide, Tomihiko; Ito, Naoto; Sugiyama, Makoto; Yoshikawa, Tetsushi; Murata, Takayuki; Taniguchi, Koki

2018-04-18

An entirely plasmid-based reverse genetics system for rotaviruses was established very recently. We improved the reverse genetics system to generate recombinant rotavirus by transfecting only 11 cDNA plasmids for its 11 gene segments under the condition of increasing the ratio of the cDNA plasmids for NSP2 and NSP5 genes. Utilizing this highly efficient system, we then engineered infectious recombinant rotaviruses expressing bioluminescent (NanoLuc luciferase) and fluorescent (EGFP and mCherry) reporters. These recombinant rotaviruses expressing reporters remained genetically stable during serial passages. Our reverse genetics approach and recombinant rotaviruses carrying reporter genes will be great additions to the tool kit for studying the molecular virology of rotavirus, and for developing future next-generation vaccines and expression vectors. IMPORTANCE Rotavirus is one of the most important pathogens causing severe gastroenteritis in young children worldwide. In this paper, we describe a robust and simple reverse genetics system based on only rotavirus cDNAs, and its application for engineering infectious recombinant rotaviruses harboring bioluminescent (NanoLuc) and fluorescent (EGFP and mCherry) protein genes. This highly efficient reverse genetics system and recombinant RVAs expressing reporters could be powerful tools for the study of different aspects of rotavirus replication. Furthermore, they may be useful for next-generation vaccine production for this medically important virus. Copyright © 2018 American Society for Microbiology.

A General Tool for Engineering the NAD/NADP Cofactor Preference of Oxidoreductases.

PubMed

Cahn, Jackson K B; Werlang, Caroline A; Baumschlager, Armin; Brinkmann-Chen, Sabine; Mayo, Stephen L; Arnold, Frances H

2017-02-17

The ability to control enzymatic nicotinamide cofactor utilization is critical for engineering efficient metabolic pathways. However, the complex interactions that determine cofactor-binding preference render this engineering particularly challenging. Physics-based models have been insufficiently accurate and blind directed evolution methods too inefficient to be widely adopted. Building on a comprehensive survey of previous studies and our own prior engineering successes, we present a structure-guided, semirational strategy for reversing enzymatic nicotinamide cofactor specificity. This heuristic-based approach leverages the diversity and sensitivity of catalytically productive cofactor binding geometries to limit the problem to an experimentally tractable scale. We demonstrate the efficacy of this strategy by inverting the cofactor specificity of four structurally diverse NADP-dependent enzymes: glyoxylate reductase, cinnamyl alcohol dehydrogenase, xylose reductase, and iron-containing alcohol dehydrogenase. The analytical components of this approach have been fully automated and are available in the form of an easy-to-use web tool: Cofactor Specificity Reversal-Structural Analysis and Library Design (CSR-SALAD).

Cheaper Adjoints by Reversing Address Computations

DOE PAGES

Hascoët, L.; Utke, J.; Naumann, U.

2008-01-01

The reverse mode of automatic differentiation is widely used in science and engineering. A severe bottleneck for the performance of the reverse mode, however, is the necessity to recover certain intermediate values of the program in reverse order. Among these values are computed addresses, which traditionally are recovered through forward recomputation and storage in memory. We propose an alternative approach for recovery that uses inverse computation based on dependency information. Address storage constitutes a significant portion of the overall storage requirements. An example illustrates substantial gains that the proposed approach yields, and we show use cases in practical applications.

14 CFR 25.933 - Reversing systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... analysis or testing, or both, for propeller systems that allow propeller blades to move from the flight low... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... position; and (ii) The airplane is capable of continued safe flight and landing under any possible position...

14 CFR 25.933 - Reversing systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... analysis or testing, or both, for propeller systems that allow propeller blades to move from the flight low... reversal in flight the engine will produce no more than flight idle thrust. In addition, it must be shown... position; and (ii) The airplane is capable of continued safe flight and landing under any possible position...

Investigation of two-dimensional wedge exhaust nozzles for advanced aircraft

NASA Technical Reports Server (NTRS)

Maiden, D. L.; Petit, J. E.

1975-01-01

Two-dimensional wedge nozzle performance characteristics were investigated in a series of wind-tunnel tests. An isolated single-engine/nozzle model was used to study the effects of internal expansion area ratio, aftbody cowl boattail angle, and wedge length. An integrated twin-engine/nozzle model, tested with and without empenage surfaces, included cruise, acceleration, thrust vectoring and thrust reversing nozzle operating modes. Results indicate that the thrust-minus-aftbody drag performance of the twin two-dimensional nozzle integration is significantly higher, for speeds greater than Mach 0.8, than the performance achieved with twin axisymmetric nozzle installations. Significant jet-induced lift was obtained on an aft-mounted lifting surface using a cambered wedge center body to vector thrust. The thrust reversing capabilities of reverser panels installed on the two-dimensional wedge center body were very effective for static or in-flight operation.

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

PubMed

Lu, Kai; Gordon, Richard; Cao, Tong

2015-03-01

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

Pollution Reduction Technology Program, Turboprop Engines, Phase 1

NASA Technical Reports Server (NTRS)

Anderson, R. D.; Herman, A. S.; Tomlinson, J. G.; Vaught, J. M.; Verdouw, A. J.

1976-01-01

Exhaust pollutant emissions were measured from a 501-D22A turboprop engine combustor and three low emission combustor types -- reverse flow, prechamber, and staged fuel, operating over a fuel-air ratio range of .0096 to .020. The EPAP LTO cycle data were obtained for a total of nineteen configurations. Hydrocarbon emissions were reduced from 15.0 to .3 lb/1000 Hp-Hr/cycle, CO from 31.5 to 4.6 lb/1000 Hp-Hr/cycle with an increase in NOx of 17 percent, which is still 25% below the program goal. The smoke number was reduced from 59 to 17. Emissions given here are for the reverse flow Mod. IV combustor which is the best candidate for further development into eventual use with the 501-D22A turboprop engine. Even lower emissions were obtained with the advanced technology combustors.

Mergers and innovation in the pharmaceutical industry.

PubMed

Comanor, William S; Scherer, F M

2013-01-01

Conflicting trends confound the pharmaceutical industry. The productivity of pharmaceutical innovation has declined in recent years. At the same time, the cohort of large companies who are the leading engines of pharmaceutical R&D has become increasingly concentrated. The concurrent presence of these trends is not sufficient to determine causation. In response to lagging innovation prospects, some companies have sought refuge in mergers and acquisitions to disguise their dwindling prospects or gain R&D synergies. On the other hand, the increased concentration brought on by recent mergers may have contributed to the declining rate of innovation. In this paper, we consider the second of these causal relationships: the likely impact of the recent merger wave among the largest pharmaceutical companies on the rate of innovation. In other words, have recent mergers, which may have been taken in response to lagging innovation, represented a self-defeating strategy that only made industry outcomes worse? Copyright © 2012 Elsevier B.V. All rights reserved.

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

Parameter estimation in spiking neural networks: a reverse-engineering approach.

PubMed

Rostro-Gonzalez, H; Cessac, B; Vieville, T

2012-04-01

This paper presents a reverse engineering approach for parameter estimation in spiking neural networks (SNNs). We consider the deterministic evolution of a time-discretized network with spiking neurons, where synaptic transmission has delays, modeled as a neural network of the generalized integrate and fire type. Our approach aims at by-passing the fact that the parameter estimation in SNN results in a non-deterministic polynomial-time hard problem when delays are to be considered. Here, this assumption has been reformulated as a linear programming (LP) problem in order to perform the solution in a polynomial time. Besides, the LP problem formulation makes the fact that the reverse engineering of a neural network can be performed from the observation of the spike times explicit. Furthermore, we point out how the LP adjustment mechanism is local to each neuron and has the same structure as a 'Hebbian' rule. Finally, we present a generalization of this approach to the design of input-output (I/O) transformations as a practical method to 'program' a spiking network, i.e. find a set of parameters allowing us to exactly reproduce the network output, given an input. Numerical verifications and illustrations are provided.

Topology reconstruction for B-Rep modeling from 3D mesh in reverse engineering applications

NASA Astrophysics Data System (ADS)

Bénière, Roseline; Subsol, Gérard; Gesquière, Gilles; Le Breton, François; Puech, William

2012-03-01

Nowadays, most of the manufactured objects are designed using CAD (Computer-Aided Design) software. Nevertheless, for visualization, data exchange or manufacturing applications, the geometric model has to be discretized into a 3D mesh composed of a finite number of vertices and edges. But, in some cases, the initial model may be lost or unavailable. In other cases, the 3D discrete representation may be modified, for example after a numerical simulation, and does not correspond anymore to the initial model. A reverse engineering method is then required to reconstruct a 3D continuous representation from the discrete one. In previous work, we have presented a new approach for 3D geometric primitive extraction. In this paper, to complete our automatic and comprehensive reverse engineering process, we propose a method to construct the topology of the retrieved object. To reconstruct a B-Rep model, a new formalism is now introduced to define the adjacency relations. Then a new process is used to construct the boundaries of the object. The whole process is tested on 3D industrial meshes and bring a solution to recover B-Rep models.

Data and Analysis Center for Software: An IAC in Transition.

DTIC Science & Technology

1983-06-01

reviewed and is approved for publication. * APPROVEDt Proj ect Engineer . JOHN J. MARCINIAK, Colonel, USAF Chief, Command and Control Division . FOR THE CO...SUPPLEMENTARY NOTES RADC Project Engineer : John Palaimo (COEE) It. KEY WORDS (Conilnuo n rever*e aide if necessary and identify by block numober...Software Engineering Software Technology Information Analysis Center Database Scientific and Technical Information 20. ABSTRACT (Continue on reverse side It

Enzyme engineering through evolution: thermostable recombinant group II intron reverse transcriptases provide new tools for RNA research and biotechnology.

PubMed

Collins, Kathleen; Nilsen, Timothy W

2013-08-01

Current investigation of RNA transcriptomes relies heavily on the use of retroviral reverse transcriptases. It is well known that these enzymes have many limitations because of their intrinsic properties. This commentary highlights the recent biochemical characterization of a new family of reverse transcriptases, those encoded by group II intron retrohoming elements. The novel properties of these enzymes endow them with the potential to revolutionize how we approach RNA analyses.

Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology.

PubMed

Das, Arya A; Ajayakumar Darsana, T; Jacob, Elizabeth

2017-03-01

Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments. A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies. Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material . liz.csir@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

NASA Researcher Examines an Aircraft Model with a Four-Fan Thrust Reverser

NASA Image and Video Library

1972-03-21

National Aeronautics and Space Administration (NASA) researcher John Carpenter inspects an aircraft model with a four-fan thrust reverser which would be studied in the 9- by 15-Foot Low Speed Wind Tunnel at the Lewis Research Center. Thrust reversers were introduced in the 1950s as a means for slowing high-speed jet aircraft during landing. Engineers sought to apply the technology to Vertical and Short Takeoff and Landing (VSTOL) aircraft in the 1970s. The new designs would have to take into account shorter landing areas, noise levels, and decreased thrust levels. A balance was needed between the thrust reverser’s efficiency, its noise generation, and the engine’s power setting. This model underwent a series of four tests in the 9- by 15-foot tunnel during April and May 1974. The model, with a high-wing configuration and no tail, was equipped with four thrust-reverser engines. The investigations included static internal aerodynamic tests on a single fan/reverser, wind tunnel isolated fan/reverser thrust tests, installation effects on a four-fan airplane model in a wind tunnel, and single reverser acoustic tests. The 9-by 15 was built inside the return leg of the 8- by 6-Foot Supersonic Wind Tunnel in 1968. The facility generates airspeeds from 0 to 175 miles per hour to evaluate the aerodynamic performance and acoustic characteristics of nozzles, inlets, and propellers, and investigate hot gas re-ingestion of advanced VSTOL concepts. John Carpenter was a technician in the Wind Tunnels Service Section of the Test Installations Division.

77 FR 7518 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... report that the top 3 inches of the aero/fire seals of the blocker doors on the thrust reverser torque... aero/fire seals of the blocker doors on the thrust reverser torque boxes on the engines, and replacing affected aero/fire seals with new, improved aero/fire seals. We are issuing this AD to prevent a fire in...

Teaching Mass Transfer and Filtration Using Crossflow Reverse Osmosis and Nanofiltration: An Experiment for the Undergraduate Unit Operations Lab

ERIC Educational Resources Information Center

Anastasio, Daniel; McCutcheon, Jeffrey

2012-01-01

A crossflow reverse osmosis (RO) system was built for a senior-level chemical engineering unit operations laboratory course. Intended to teach students mass transfer fundamentals related to membrane separations, students tested several commercial desalination membranes, measuring water flux and salt rejections at various pressures, flow rates, and…

Physics at the International Science and Engineering Fair.

ERIC Educational Resources Information Center

Walker, Jearl

1979-01-01

A judge for the physics projects for the 1979 International Science and Engineering Fair describes many of the more popular science projects. Projects described include the following: carbon dioxide and helium-neon lasers, reverse flame investigations, holography, construction of a magnetic bottle to confine plasma, and aerodynamic drag. (BT)

The tendency for social submission predicts superior cognitive performance in previously isolated male mice

PubMed Central

Matzel, Louis D.; Kolata, Stefan; Light, Kenneth; Sauce, Bruno

2016-01-01

The imposition of subordination may negatively impact cognitive performance in common social settings (e.g., the classroom), and likewise, laboratory studies of animals indicate that the stress associated with social defeat can impair cognitive performance. It is less clear whether an animal’s predisposition for social subordination (i.e., a tendency that is expressed prior to experience with social defeat) is related to its cognitive abilities (e.g., “general” intelligence). Using genetically diverse CD-1 male mice, here we determined that in the absence of adult experience with social hierarchies or social defeat, the predisposition for social subordination was associated with superior general cognitive ability (aggregate performance across a battery of five learning tasks). The tendency for social subordination was not dependent on the mice’ body weight, but both general cognitive ability and the tendency for social subordination were directly related to high stress reactivity (i.e., free corticosterone elevations induced by mild stress). This pattern of results suggests that submissive behavior and sensitivity to stress may be associated with superior cognitive potential, and this can reflect a native predisposition that precedes exposure to social pressures. More broadly, these results raise the possibility that socially subordinate animals evolved compensatory strategies to facilitate their survival, and that absent the imposition of subordination, normally submissive individuals may be better prepared for cognitive/academic achievement. PMID:27457190

Transonic Fan/Compressor Rotor Design Study. Volume 5

DTIC Science & Technology

1982-02-01

Fan Aircraft Engines Compressor Blade Thickness Rotor Camber Distribution Aerodesign Throat Margin Aerodynamics 20. ABStTRACT (Continue n reverse...Technology Branch FOR THE COMNANDER H. IV N BUS Director, Turbine Engine Division A If your address has changed, if you wish to be removed from our...ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK General Electric Ctmpany AREA & WORK UNIT NUMBERS Aircraft Engine Business Group Project 2307

Quiet Clean Short-haul Experimental Engine (QCSEE) Over-The-Wing (OTW) propulsion systems test report. Volume 4: Acoustic performance

NASA Technical Reports Server (NTRS)

Stimpert, D. L.

1979-01-01

A series of acoustic tests were conducted on the over the wing engine. These tests evaluated the fully suppressed noise levels in forward and reverse thrust operation and provided insight into the component noise sources of the engine plus the suppression achieved by various components. System noise levels using the contract specified calculation procedure indicate that the in-flight noise level on a 152 m sideline at takeoff and approach are 97.2 and 94.6 EPNdB, respectively, compared to a goal of 95.0 EPNdB. In reverse thrust, the system noise level was 106.1 PNdB compared to a goal of 100 PNdB. Baseline source noise levels agreed very well with pretest predictions. Inlet-radiated noise suppression of 14 PNdB was demonstrated with the high throat Mach number inlet at 0.79 throat Mach number.

John N. Crouse--crusader and mitigator.

PubMed

Schulein, Thomas M

2005-11-01

During the last part of the nineteenth century, John N. Crouse fought hard to defeat the process patents of the International Tooth Crown Company. Prior to that time he engaged in a lucrative dental practice, was a President of the American Dental Association and was a highly respected dentist in Chicago. In the midst of his fight against the International Tooth Crown Company, Crouse organized a dental supply business and a dental journal. After the defeat of the Tooth Crown Company's patents, in an interesting turn of events, Crouse appeared to form an alliance with a party who formed another threat to the dental profession by foisting his patents on it. This article traces the life of a noteworthy man who could rightly be placed among the most important figures in American dentistry.

"Our reach is wide by any corporate standard": how the tobacco industry helped defeat the Clinton health plan and why it matters now.

PubMed

Tesler, Laura E; Malone, Ruth E

2010-07-01

Contemporary health care reformers, like those who promoted the failed Clinton era plan, face opposition from multiple corporate interests. However, scant literature has examined how relationships between corporations and other stakeholders, such as think tanks and advocacy groups, shape health care reform debate. We show how the 2 biggest US tobacco companies, Philip Morris and RJ Reynolds, and their trade association coordinated in mobilizing ideologically diverse constituencies to help defeat the Clinton plan. Unwittingly perhaps, some reform supporters advanced the tobacco industry's public relations blitz, contributing to perceptions of public opposition to the plan. As the current reform debate unfolds, this case highlights the importance of funding transparency for interpreting the activities of think tanks, advocacy groups, and "grassroots" movements.

Small-scale heat detection using catalytic microengines irradiated by laser

NASA Astrophysics Data System (ADS)

Liu, Zhaoqian; Li, Jinxing; Wang, Jiao; Huang, Gaoshan; Liu, Ran; Mei, Yongfeng

2013-01-01

We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection.We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32494f

[Veneer computer aided design based on reverse engineering technology].

PubMed

Liu, Ming-li; Chen, Xiao-dong; Wang, Yong

2012-03-01

To explore the computer aided design (CAD) method of veneer restoration, and to assess if the solution can help prosthesis meet morphology esthetics standard. A volunteer's upper right central incisor needed to be restored with veneer. Super hard stone models of patient's dentition (before and after tooth preparation) were scanned with the three-dimensional laser scanner. The veneer margin was designed as butt-to-butt type. The veneer was constructed using reverse engineering (RE) software. The technique guideline of veneers CAD was explore based on RE software, and the veneers was smooth, continuous and symmetrical, which met esthetics construction needs. It was a feasible method to reconstruct veneer restoration based on RE technology.

Update of GRASP/Ada reverse engineering tools for Ada

NASA Technical Reports Server (NTRS)

Cross, James H., II

1992-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation of Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAS 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3, the prototype was evaluated by software engineering students at Auburn University and then updated with significant enhancements to the user interface including editing capabilities. Version 3.2 of the prototype was prepared for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical application.

Federal STEM Policy and Politics and Their Impact on Astronomy EPO: Reflections and Provocations

NASA Astrophysics Data System (ADS)

Schultz, G.; Storksdieck, M.; Canright, S.

2015-11-01

The federal government invests more than $3 billion each year across its various units in supporting STEM education and outreach. Efforts in recent years to understand and better coordinate these investments have resulted in considerable pushback, particularly those efforts that aimed at consolidation and elimination of programs deemed ineffective or duplicative. While initial plans to streamline federal STEM education were defeated, many agencies nonetheless saw cuts and elimination, and a high-level effort to coordinate STEM education at the cross-agency level is now gaining steam (CoSTEM: Committee on Science, Technology, Engineering, and Mathematics Education). What do all of these developments mean for education and public outreach in astronomy and related fields? How should this community operate within the opportunities and threats that CoSTEM might pose? Former director of the National Academy of Science's Board on Science Education, and now director of the Center for Research on Lifelong STEM Learning, Martin Storksdieck, reflected on past and recent developments from the perspective of a close observer, and from the perspective of someone who has been involved in astronomy education research and evaluation for nearly 20 years. Shelley Canright, Senior Advisor for Education Integration at the NASA Office of Education, shared her insights and perspectives with respect to CoSTEM and EPO, in particular from co-chairing the Federal Coordination in Science, Technology, Engineering, and Mathematics Education (FC-STEM) group.

Coupling of protein localization and cell movements by a dynamically localized response regulator in Myxococcus xanthus

PubMed Central

Leonardy, Simone; Freymark, Gerald; Hebener, Sabrina; Ellehauge, Eva; Søgaard-Andersen, Lotte

2007-01-01

Myxococcus xanthus cells harbor two motility machineries, type IV pili (Tfp) and the A-engine. During reversals, the two machineries switch polarity synchronously. We present a mechanism that synchronizes this polarity switching. We identify the required for motility response regulator (RomR) as essential for A-motility. RomR localizes in a bipolar, asymmetric pattern with a large cluster at the lagging cell pole. The large RomR cluster relocates to the new lagging pole in parallel with cell reversals. Dynamic RomR localization is essential for cell reversals, suggesting that RomR relocalization induces the polarity switching of the A-engine. The analysis of RomR mutants shows that the output domain targets RomR to the poles and the receiver domain is essential for dynamic localization. The small GTPase MglA establishes correct RomR polarity, and the Frz two-component system regulates dynamic RomR localization. FrzS localizes with Tfp at the leading pole and relocates in an Frz-dependent manner to the opposite pole during reversals; FrzS and RomR localize and oscillate independently. The Frz system synchronizes these oscillations and thus the synchronous polarity switching of the motility machineries. PMID:17932488

14 CFR 25.1103 - Induction system ducts and air duct systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... between which relative motion could exist must have means for flexibility. (d) For turbine engine and... stage of the engine supercharger and of the auxiliary power unit compressor must have a drain to prevent... compartment to prevent hot gas reverse flow from burning through auxiliary power unit ducts and entering any...

DC-9 Flight Demonstration Program with Refanned JT8D Engines. Volume 3; Performance and Analysis

NASA Technical Reports Server (NTRS)

1975-01-01

The JT8D-109 engine has a sea level static, standard day bare engine takeoff thrust of 73,840 N. At sea level standard day conditions the additional thrust of the JT8D-109 results in 2,040 kg additional takeoff gross weight capability for a given field length. Range loss of the DC-9 Refan airplane for long range cruise was determined. The Refan airplane demonstrated stall, static longitudinal stability, longitudinal control, longitudinal trim, minimum control speeds, and directional control characteristics similar to the DC-9-30 production airplane and complied with airworthiness requirements. Cruise, climb, and thrust reverser performance were evaluated. Structural and dynamic ground test, flight test and analytical results substantiate Refan Program requirements that the nacelle, thrust reverser hardware, and the airplane structural modifications are flightworthy and certifiable and that the airplane meets flutter speed margins. Estimated unit cost of a DC-9 Refan retrofit program is 1.338 million in mid-1975 dollars with about an equal split in cost between airframe and engine.

An airline study of advanced technology requirements for advanced high speed commercial transport engines. 1: Engine design study assessment

NASA Technical Reports Server (NTRS)

Sallee, G. P.

1973-01-01

The advanced technology requirements for an advanced high speed commercial tranport engine are presented. The results of the phase 1 study effort cover the following areas: (1) statement of an airline's major objectives for future transport engines, (2) airline's method of evaluating engine proposals, (3) description of an optimum engine for a long range subsonic commercial transport including installation and critical design features, (4) discussion of engine performance problems and experience with performance degradation, (5) trends in engine and pod prices with increasing technology and objectives for the future, (6) discussion of the research objectives for composites, reversers, advanced components, engine control systems, and devices to reduce the impact of engine stall, and (7) discussion of the airline objectives for noise and pollution reduction.

Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.

PubMed

De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

2013-01-01

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.

Reverse engineering and analysis of large genome-scale gene networks

PubMed Central

Aluru, Maneesha; Zola, Jaroslaw; Nettleton, Dan; Aluru, Srinivas

2013-01-01

Reverse engineering the whole-genome networks of complex multicellular organisms continues to remain a challenge. While simpler models easily scale to large number of genes and gene expression datasets, more accurate models are compute intensive limiting their scale of applicability. To enable fast and accurate reconstruction of large networks, we developed Tool for Inferring Network of Genes (TINGe), a parallel mutual information (MI)-based program. The novel features of our approach include: (i) B-spline-based formulation for linear-time computation of MI, (ii) a novel algorithm for direct permutation testing and (iii) development of parallel algorithms to reduce run-time and facilitate construction of large networks. We assess the quality of our method by comparison with ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks) and GeneNet and demonstrate its unique capability by reverse engineering the whole-genome network of Arabidopsis thaliana from 3137 Affymetrix ATH1 GeneChips in just 9 min on a 1024-core cluster. We further report on the development of a new software Gene Network Analyzer (GeNA) for extracting context-specific subnetworks from a given set of seed genes. Using TINGe and GeNA, we performed analysis of 241 Arabidopsis AraCyc 8.0 pathways, and the results are made available through the web. PMID:23042249

House again passes ban on abortions at military facilities.

PubMed

1996-05-31

Voting 192-225 on May 14, the House defeated an effort to reverse the current prohibition on privately funded abortions at military facilities except in cases of life endangerment, rape, or incest. Introduced by pro-choice Representatives Rosa DeLauro (D-CT), Jane Harman (D-CA), and Mike Ward (D-KY) and mixed record Representative Peter Torkildsen (R-MA), the amendment to the National Defense Authorization Act (HR 3230) would have repealed restrictive language in the statute that governs the Department of Defense (DOD). Floor action on the provision of non-government-funded abortions mirrored Representative DeLauro's failed attempts to strike the onerous provision during the mark-up process for HR 3230, which received final House approval in a 272-153 vote on May 15. The House National Security Committee voted 26-20 against removing the abortion restriction on May 1, six days after a similar 11-5 vote by the Subcommittee on Military Personnel. The near ban on abortion services has been in effect since December of last year, when the DOD spending bill was implemented; President Clinton signed the legislation permanently encoding the restriction into law in February (see RFN IV/22, V/3-4). Upon taking office in January 1993, President Clinton had issued an executive memorandum directing the Secretary of Defense to reverse the ban on the performance of non-lifesaving, privately funded abortions at military facilities, which had been instituted through agency action in mid-1988 (see RFN II/3, IV/13). The DOD authorization statute has prohibited the use of federal funds for abortions except in cases of life endangerment for more than a decade. full text

Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

PubMed

Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

2008-02-19

Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

Reversible S-nitrosylation in an engineered azurin

DOE PAGES

Tian, Shiliang; Liu, Jing; Cowley, Ryan E.; ...

2016-04-25

Here, S-Nitrosothiols are known as reagents for NO storage and transportation and as regulators in many physiological processes. Although the S-nitrosylation catalysed by haem proteins is well known, no direct evidence of S-nitrosylation in copper proteins has been reported. Here, we report reversible insertion of NO into a copper–thiolate bond in an engineered copper centre in Pseudomonas aeruginosa azurin by rational design of the primary coordination sphere and tuning its reduction potential by deleting a hydrogen bond in the secondary coordination sphere. The results not only provide the first direct evidence of S-nitrosylation of Cu(II)-bound cysteine in metalloproteins, but alsomore » shed light on the reaction mechanism and structural features responsible for stabilizing the elusive Cu(I)–S(Cys)NO species. The fast, efficient and reversible S-nitrosylation reaction is used to demonstrate its ability to prevent NO inhibition of cytochrome bo 3 oxidase activity by competing for NO binding with the native enzyme under physiologically relevant conditions.« less

Rho-associated kinase (ROCK) inhibition reverses low cell activity on hydrophobic surfaces.

PubMed

Tian, Yu Shun; Kim, Hyun Jung; Kim, Hyun-Man

2009-08-28

Hydrophobic polymers do not offer an adequate scaffold surface for cells to attach, migrate, proliferate, and differentiate. Thus, hydrophobic scaffolds for tissue engineering have traditionally been physicochemically modified to enhance cellular activity. However, modifying the surface by chemical or physical treatment requires supplementary engineering procedures. In the present study, regulation of a cell signal transduction pathway reversed the low cellular activity on a hydrophobic surface without surface modification. Inhibition of Rho-associated kinase (ROCK) by Y-27632 markedly enhanced adhesion, migration, and proliferation of osteoblastic cells cultured on a hydrophobic polystyrene surface. ROCK inhibition regulated cell-cycle-related molecules on the hydrophobic surface. This inhibition also decreased expression of the inhibitors of cyclin-dependent kinases such as p21(cip1) and p27(kip1) and increased expression of cyclin A and D. These results indicate that defective cellular activity on the hydrophobic surface can be reversed by the control of a cell signal transduction pathway without physicochemical surface modification.

Electric-field-driven magnetization reversal in square-shaped nanomagnet-based multiferroic heterostructure

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

Peng, Ren-Ci; Nan, Ce-Wen, E-mail: jzw12@psu.edu, E-mail: cwnan@tsinghua.edu.cn; Wang, J. J., E-mail: jzw12@psu.edu, E-mail: cwnan@tsinghua.edu.cn

Based on phase field modeling and thermodynamic analysis, purely electric-field-driven magnetization reversal was shown to be possible in a multiferroic heterostructure of a square-shaped amorphous Co{sub 40}Fe{sub 40}B{sub 20} nanomagnet on top of a ferroelectric layer through electrostrain. The reversal is made possible by engineering the mutual interactions among the built-in uniaxial magnetic anisotropy, the geometry-dependent magnetic configuration anisotropy, and the magnetoelastic anisotropy. Particularly, the incorporation of the built-in uniaxial anisotropy made it possible to reverse magnetization with one single unipolar electrostrain pulse, which is simpler than previous designs involving the use of bipolar electrostrains and may alleviate ferroelectric fatigue.more » Critical conditions for triggering the magnetization reversal are identified.« less

RAS Initiative - Community Outreach

Cancer.gov

Through community and technical collaborations, workshops and symposia, and the distribution of reference reagents, the RAS Initiative seeks to increase the sharing of knowledge and resources essential to defeating cancers caused by mutant RAS genes.

Static Performance of Six Innovative Thrust Reverser Concepts for Subsonic Transport Applications: Summary of the NASA Langley Innovative Thrust Reverser Test Program

NASA Technical Reports Server (NTRS)

Asbury, Scott C.; Yetter, Jeffrey A.

2000-01-01

The NASA Langley Configuration Aerodynamics Branch has conducted an experimental investigation to study the static performance of innovative thrust reverser concepts applicable to high-bypass-ratio turbofan engines. Testing was conducted on a conventional separate-flow exhaust system configuration, a conventional cascade thrust reverser configuration, and six innovative thrust reverser configurations. The innovative thrust reverser configurations consisted of a cascade thrust reverser with porous fan-duct blocker, a blockerless thrust reverser, two core-mounted target thrust reversers, a multi-door crocodile thrust reverser, and a wing-mounted thrust reverser. Each of the innovative thrust reverser concepts offer potential weight savings and/or design simplifications over a conventional cascade thrust reverser design. Testing was conducted in the Jet-Exit Test Facility at NASA Langley Research Center using a 7.9%-scale exhaust system model with a fan-to-core bypass ratio of approximately 9.0. All tests were conducted with no external flow and cold, high-pressure air was used to simulate core and fan exhaust flows. Results show that the innovative thrust reverser concepts achieved thrust reverser performance levels which, when taking into account the potential for system simplification and reduced weight, may make them competitive with, or potentially more cost effective than current state-of-the-art thrust reverser systems.

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

Oler, Kiri J.; Miller, Carl H.

In this paper, we present a methodology for reverse engineering integrated circuits, including a mathematical verification of a scalable algorithm used to generate minimal finite state machine representations of integrated circuits.

76 FR 62649 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

.../fire seals of the blocker doors on the thrust reverser torque boxes on the engines, and replacing affected aero/fire seals with new, improved aero/fire seals. That second supplemental NPRM was prompted by a report that the top 3 inches of the aero/fire seals of the blocker doors on the thrust reverser...

Career Profiles- Aero-Mechanical Design- Operations Engineering Branch

NASA Image and Video Library

2015-10-26

NASA Armstrong’s Aeromechanical Design Group provides mechanical design solutions ranging from research and development to ground support equipment. With an aerospace or mechanical engineering background, team members use the latest computer-aided design software to create one-of-kind parts, assemblies, and drawings, and aid in the design’s fabrication and integration. Reverse engineering and inspection of Armstrong’s fleet of aircraft is made possible by using state-of-the-art coordinate measuring machines and laser scanning equipment.

Pollution reduction technology program for turboprop engines

NASA Technical Reports Server (NTRS)

Tomlinson, J. G.

1977-01-01

The reduction of CO, HC, and smoke emissions while maintaining acceptable NO(x) emissions without affecting fuel consumption, durability, maintainability, and safety was accomplished. Component combustor concept screening directed toward the demonstration of advanced combustor technology required to meet the EPA exhaust emissions standards for class P2 turboprop engines was covered. The combustion system for the Allison 501-D22A engine was used, and three combustor design concepts - reverse flow, prechamber, and staged fuel were evaluated.

48 CFR 3009.108-7003 - Special rules.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... (1) Certain rights shall be treated as stocks to the extent necessary to reflect the present value of... present value of the transaction or to disregard transactions whose recognition would defeat the purpose...

38 CFR Appendix B to Subpart A of... - Illustrative Applications

Code of Federal Regulations, 2012 CFR

2012-07-01

... such grants the assurance will apply to patients, to interns, residents, student nurses, and other... approvals on criteria which have the effect of defeating or of substantially impairing accomplishment of the...

38 CFR Appendix B to Subpart A of... - Illustrative Applications

Code of Federal Regulations, 2013 CFR

2013-07-01

... such grants the assurance will apply to patients, to interns, residents, student nurses, and other... approvals on criteria which have the effect of defeating or of substantially impairing accomplishment of the...

38 CFR Appendix B to Subpart A of... - Illustrative Applications

Code of Federal Regulations, 2014 CFR

2014-07-01

... such grants the assurance will apply to patients, to interns, residents, student nurses, and other... approvals on criteria which have the effect of defeating or of substantially impairing accomplishment of the...

Will the UK Supreme Court allow assisted dying?

PubMed

Griffith, Richard

MPs overwhelmingly voted against passing the Assisted Dying Bill into law in September 2015. The Bill was defeated by a majority of 212, despite the heartfelt pleas of many MPs to pass it into law. The size of the defeat means that it is unlikely that Parliament will consider a similar law for many years. Yet many considered the Bill their last opportunity to make assisted dying lawful. There is, however, one further possible way assisted dying could become lawful in the UK--and that would be where the Supreme Court allowed it. In this article, the author reviews the Supreme Court's decision in R (on the application of Nicklinson v Ministry of Justice [2014] and considers how likely it is that the Supreme Court will now sanction assisted dying following Parliament's refusal to enact an assisted dying law.

“Our Reach Is Wide by Any Corporate Standard”: How the Tobacco Industry Helped Defeat the Clinton Health Plan and Why It Matters Now

PubMed Central

Tesler, Laura E.

2010-01-01

Contemporary health care reformers, like those who promoted the failed Clinton era plan, face opposition from multiple corporate interests. However, scant literature has examined how relationships between corporations and other stakeholders, such as think tanks and advocacy groups, shape health care reform debate. We show how the 2 biggest US tobacco companies, Philip Morris and RJ Reynolds, and their trade association coordinated in mobilizing ideologically diverse constituencies to help defeat the Clinton plan. Unwittingly perhaps, some reform supporters advanced the tobacco industry's public relations blitz, contributing to perceptions of public opposition to the plan. As the current reform debate unfolds, this case highlights the importance of funding transparency for interpreting the activities of think tanks, advocacy groups, and “grassroots” movements. PMID:20466958

Tobacco Industry Efforts to Defeat the Occupational Safety and Health Administration Indoor Air Quality Rule

PubMed Central

Bryan-Jones, Katherine; Bero, Lisa A.

2003-01-01

Objectives. We describe tobacco industry strategies to defeat the Occupational Safety and Health Administration (OSHA) Indoor Air Quality rule and the implementation of those strategies. Methods. We analyzed tobacco industry documents, public commentary on, and media coverage of the OSHA rule. Results. The tobacco industry had 5 strategies: (1) maintain scientific debate about the basis of the rule, (2) delay deliberation on the rule, (3) redefine the scope of the rule, (4) recruit and assist labor and business organizations in opposing the rule, and (5) increase media coverage of the tobacco industry position. The tobacco industry successfully implemented all 5 strategies. Conclusions. Our findings suggest that regulatory authorities must take into account the source, motivation, and validity of arguments used in the regulatory process in order to make accurately informed decisions. PMID:12660202

[Cigarette smuggling: a wide scope phenomenon only there to serve the interests of big tobacco manufacturers].

PubMed

Gauvin, Louis

2005-01-01

"Cigarette smuggling: a wide scope phenomenon only there to serve the interests of big tobacco manuafacturers" uses industry officials' quotes and documents to describe how tobacco manufacturers are involved in the organisation of smuggling and how manufacturers use smuggling in two ways: on one hand, to flood markets with cheap cigarettes and defeat governements' efforts to reduce tobacco consumption by adopting one of the most efficient public health measures (ie: high taxation of tobacco products) and on the other hand, by using the false threat of increased contraband to scare politicians and prevent them from adopting strong fiscal policies. The Framework Convention on Tobacco Control (FCTC) with a protocol on smuggling and the collaboration between international agencies is a means to counter and defeat the tobacco industry attemps at sabotaging efficient public health measures.

Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress.

PubMed

Bharwani, Aadil; Mian, M Firoz; Surette, Michael G; Bienenstock, John; Forsythe, Paul

2017-01-11

Stress-related disorders involve systemic alterations, including disruption of the intestinal microbial community. Given the putative connections between the microbiota, immunity, neural function, and behaviour, we investigated the potential for microbe-induced gut-to-brain signalling to modulate the impact of stress on host behaviour and immunoregulation. Male C57BL/6 mice treated orally over 28 days with either Lactobacillus rhamnosus (JB-1) ™ or vehicle were subjected to chronic social defeat and assessed for alterations in behaviour and immune cell phenotype. 16S rRNA sequencing and mass spectrometry were employed to analyse the faecal microbial community and metabolite profile. Treatment with JB-1 decreased stress-induced anxiety-like behaviour and prevented deficits in social interaction with conspecifics. However, JB-1 did not alter development of aggressor avoidance following social defeat. Microbial treatment attenuated stress-related activation of dendritic cells while increasing IL-10+ regulatory T cells. Furthermore, JB-1 modulated the effect of stress on faecal metabolites with neuroactive and immunomodulatory properties. Exposure to social defeat altered faecal microbial community composition and reduced species richness and diversity, none of which was prevented by JB-1. Stress-related microbiota disruptions persisted in vehicle-treated mice for 3 weeks following stressor cessation. These data demonstrate that despite the complexity of the gut microbiota, exposure to a single microbial strain can protect against certain stress-induced behaviours and systemic immune alterations without preventing dysbiosis. This work supports microbe-based interventions for stress-related disorders.

Psychological pathway to suicidal ideation among men who have sex with men in Shanghai, China: A structural equation model.

PubMed

Li, Rui; Cai, Yong; Wang, Ying; Gan, Feng; Shi, Rong

2016-12-01

We aimed to explore the relationships and develop an inter-theoretical model among psychological variables in the progression to suicidal ideation among men who have sex with men (MSM). A cross-sectional study was conducted among 547 MSM in four districts in Shanghai from March to May in 2014. Socio-demographic, psychological, and behavioral information of the participants was collected. A structural equation model (SEM)-Path Analysis was constructed to interpret the intricate relationships among various psychological variables. Suicidal ideation among MSM during the past year was 10.6%. The developed model agreed well with existing suicide models and had a good fit to the data (χ 2 /df = 2.497, comparative fit index = 0.983, root mean squared error of approximation = 0.052). Suicidal ideation was predicted by perceived defeat and entrapment (β = 0.21, p < 0.001), which was in turn predicted by temperament (β = 0.60, p < 0.001) and perceived social support (β = 0.34, p < 0.001). Perceived social support fully mediated the relationships among mood states, perceived social status, and perceived defeat and entrapment. MSM with certain types of temperament might be predisposed to a higher perception of defeat and entrapment. Perceived social support can effectively alleviate the negative appraisals and emotions and lower the risk for suicidal ideation among MSM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Virtual Parts Engineering Research Center

DTIC Science & Technology

2010-05-20

engineering 10 materials. High strength alloys , composites (polymer composites and metallic composites), and the like cannot merely be replaced by...ceramics, smart materials, shape memory alloys , super plastic materials and nano- structured materials may be more appropriate substitutes in a reverse...molding process using thermosetting Bakelite. For remanufacturing the part in small quantities, machining has been identified as the most economical

The High School Environment and the Gender Gap in Science and Engineering

ERIC Educational Resources Information Center

Legewie, Joscha; DiPrete, Thomas A.

2014-01-01

Despite the striking reversal of the gender gap in education, women pursue science, technology, engineering, and mathematics (STEM) degrees at much lower rates than those of their male peers. This study extends existing explanations for these gender differences and examines the role of the high school context for plans to major in STEM fields.…

76 FR 63159 - Airworthiness Directives; Airbus Model A330-243F Airplanes Equipped With Rolls Royce Trent 700...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

... Airworthiness Directives; Airbus Model A330-243F Airplanes Equipped With Rolls Royce Trent 700 Series Engines... Branch, ANM-116, Transport Airplane Directorate, FAA, 1601 Lind Avenue, SW., Renton, Washington 98057... assemblies and along the beam structure of the right and left engine thrust reversers, detailed inspection...

Common Database Interface for Heterogeneous Software Engineering Tools.

DTIC Science & Technology

1987-12-01

SUB-GROUP Database Management Systems ;Programming(Comuters); 1e 05 Computer Files;Information Transfer;Interfaces; 19. ABSTRACT (Continue on reverse...Air Force Institute of Technology Air University In Partial Fulfillment of the Requirements for the Degree of Master of Science in Information Systems ...Literature ..... 8 System 690 Configuration ......... 8 Database Functionis ............ 14 Software Engineering Environments ... 14 Data Manager

Engines with ideal efficiency and nonzero power for sublinear transport laws

NASA Astrophysics Data System (ADS)

Koning, Jesper; Indekeu, Joseph O.

2016-11-01

It is known that an engine with ideal efficiency (η = 1 for a chemical engine and e = eCarnot for a thermal one) has zero power because a reversible cycle takes an infinite time. However, at least from a theoretical point of view, it is possible to conceive (irreversible) engines with nonzero power that can reach ideal efficiency. Here this is achieved by replacing the usual linear transport law by a sublinear one and taking the step-function limit for the particle current (chemical engine) or heat current (thermal engine) versus the applied force. It is shown that in taking this limit exact thermodynamic inequalities relating the currents to the entropy production are not violated.

Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism.

PubMed

Nemenman, Ilya; Escola, G Sean; Hlavacek, William S; Unkefer, Pat J; Unkefer, Clifford J; Wall, Michael E

2007-12-01

We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For benchmarking purposes, we generate synthetic metabolic profiles based on a well-established model for red blood cell metabolism. A variety of data sets are generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and temporal dynamics. These data sets are made available online. We use ARACNE, a mainstream algorithm for reverse engineering of transcriptional regulatory networks from gene expression data, to predict metabolic interactions from these data sets. We find that the performance of ARACNE on metabolic data is comparable to that on gene expression data.

High Pressure Reverse Flow APS Engine

NASA Technical Reports Server (NTRS)

Senneff, J. M.

1972-01-01

A design and test demonstration effort was undertaken to evaluate the concept of the reverse flow engine for the APS engine application. The 1500 lb (6672 N) thrust engine was designed to operate on gaseous hydrogen and gaseous oxygen propellants at a mixture ratio of 4 and to achieve the objective performance of 435 sec (4266 Nsec/kg) specific impulse. Superimposed durability requirements called for a million-cycle capability with 50 hours duration. The program was undertaken as a series of tasks including the initial preliminary design, design of critical test components and finally, the design and demonstration of an altitude engine which could be used interchangeably to examine operating parameters as well as to demonstrate the capability of the concept. The program results are reported with data to indicate that all of the program objectives were met or exceeded within the course of testing on the program. The analysis effort undertaken is also reported in detail and supplemented with test data in some cases where prior definitions could not be made. The results are contained of these analyses as well as the test results conducted throughout the course of the program. Finally, the test data and analytical results were combined to allow recommendations for a flight weight design. This preliminary design effort is also detailed.

TGF-β1 gene-engineered mesenchymal stem cells induce rat cartilage regeneration using nonviral gene vector.

PubMed

He, Cai-Xia; Zhang, Tian-Yuan; Miao, Pei-Hong; Hu, Zhong-Jie; Han, Min; Tabata, Yasuhiko; Hu, Yu-Lan; Gao, Jian-Qing

2012-01-01

This study evaluated the potential of utilizing transfected pTGFβ-1 gene-engineered rat mesenchymal stem cells (MSCs) using nonviral vector to promote cartilage regeneration. Pullulan-spermine was used as the nonviral gene vector and gelatin sponge was used as the scaffold. MSCs were engineered with TGF-β1 gene with either the three-dimensional (3D) reverse transfection system or the two-dimensional (2D) conventional transfection system. For the 3D reverse transfection system, pullulan-spermine/pTGF-β1 gene complexes were immobilized to the gelatin sponge, followed by the seeding of MSCs. Pullulan-spermine/pTGF-β1 gene complexes were delivered to MSCs cultured in the plate to perform the 2D conventional transfection system, and then MSCs were seeded to the gelatin sponge. Then, TGF-β1 gene-transfected MSC seeded gelatin sponge was implanted to the full-thickness cartilage defect. Compared with the control group, both groups of TGF-β1 gene-engineered MSCs improved cartilage regeneration through optical observation and histology staining. So, with pullulan-spermine as the nonviral vector, TGF-β1-gene engineered MSCs can induce cartilage regeneration in vivo. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

PubMed Central

Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-01-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

PubMed

Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-03-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Legitimating Irrelevance: Management Education in Higher Education Institutions.

ERIC Educational Resources Information Center

Crowther, David; Carter, Chris

2002-01-01

Explores why the trend in management teaching and research toward increased specialization and self-referential legitimation is ultimately self-defeating because the needs of the customers involved are changing from specialization to generalization. (EV)

7 CFR 760.106 - Equitable relief.

Code of Federal Regulations, 2010 CFR

2010-01-01

... accordance with the FCIA (7 U.S.C. 1501-1524) or (ii) Application closing date for NAP. (b) Equitable relief... intent of defeating the purposes of a program of insurance, NAP, or any other program administered under...

The Clinical Use of Hypnotic Regression and Progression in Psychotherapy.

ERIC Educational Resources Information Center

Goldberg, Bruce

1990-01-01

Discusses concept of time in therapy, presenting theoretical and clinical foundations to illustrate the validity of guiding patients into past lives and future lifetimes through hypnosis to resolve self-defeating sequences. (Author/TE)

Quiet Clean Short-haul Experimental Engine (QCSEE): The aerodynamic and mechanical design of the QCSEE under-the-wing fan

NASA Technical Reports Server (NTRS)

1977-01-01

The design, fabrication, and testing of two experimental high bypass geared turbofan engines and propulsion systems for short haul passenger aircraft are described. The aerodynamic and mechanical design of a variable pitch 1.34 pressure ratio fan for the under the wing (UTW) engine are included. The UTW fan was designed to permit rotation of the 18 composite fan blades into the reverse thrust mode of operation through both flat pitch and stall pitch directions.

Quiet Clean Short-haul Experimental Engine (QCSEE) UTW fan preliminary design

NASA Technical Reports Server (NTRS)

1975-01-01

High bypass geared turbofan engines and propulsion systems designed for short-haul passenger aircraft are described. The propulsion technology required for future externally blown flap aircraft with engines located both under the wing and over the wing is emphasized. The aerodynamic and mechanical preliminary design of the QCSEE under the wing 1.34 pressure ratio fan with variable blade pitch is presented. Design information is given for two pitch change actuation systems which will provide reverse thrust.

Double acting stirling engine phase control

DOEpatents

Berchowitz, David M.

1983-01-01

A mechanical device for effecting a phase change between the expansion and compression volumes of a double-acting Stirling engine uses helical elements which produce opposite rotation of a pair of crankpins when a control rod is moved, so the phase between two pairs of pistons is changed by +.psi. and the phase between the other two pairs of pistons is changed by -.psi.. The phase can change beyond .psi.=90.degree. at which regenerative braking and then reversal of engine rotation occurs.

Developing a Knowledge Base for Detection of Powertrain Failures by Reversibly Seeding Engine Faults

DTIC Science & Technology

2010-08-01

output, in terms of torque, speed and heat losses, can be accurately performed. Our investigation has focused on creating faulty operating conditions...open loop case”, used to measure the engine output for a given driver demand, for instance, 100% pedal); in the other case (“ closed loop ”) engine...could be changed in nine steps ranging from completely open to fully closed . Another butterfly valve was placed at the end of the exhaust pipe before

A Template Engine for Parsing Objects from Textual Representations

NASA Astrophysics Data System (ADS)

Rajković, Milan; Stanković, Milena; Marković, Ivica

2011-09-01

Template engines are widely used for separation of business and presentation logic. They are commonly used in web applications for clean rendering of HTML pages. Another area of usage is message formatting in distributed applications where they transform objects to appropriate representations. This paper explores the possibility of using templates for a reverse process—for creating objects starting from their representations. We present the prototype of engine that we have developed, and describe benefits and drawbacks of this approach.

Nanointerface-driven reversible hydrogen storage in the nanoconfined Li-N-H system

DOE PAGES

Wood, Brandon C.; Stavila, Vitalie; Poonyayant, Natchapol; ...

2017-01-20

Internal interfaces in the Li 3N/[LiNH 2 + 2LiH] solid-state hydrogen storage system alter the hydrogenation and dehydrogenation reaction pathways upon nanosizing, suppressing undesirable intermediate phases to dramatically improve kinetics and reversibility. Finally, the key role of solid interfaces in determining thermodynamics and kinetics suggests a new paradigm for optimizing complex hydrides for solid-state hydrogen storage by engineering internal microstructure.

Columbia University: Direct Reversal of Glucocorticoid Resistance by AKT inhibition in Acute Lymphoblastic Leukemia (T-ALL) | Office of Cancer Genomics

Cancer.gov

The goal of this project is to identify key druggable regulators of glucocorticoid resistance in T-ALL. To this end, a reverse-engineered T-ALL context-specific regulatory interaction network was created from a phenotypically diverse T-ALL gene expression dataset, and then this network was interrogated using master regulator analysis to find drivers of glucocorticoid resistance.

Nonlinearities in reservoir engineering: Enhancing quantum correlations

NASA Astrophysics Data System (ADS)

Hu, Xiangming; Hu, Qingping; Li, Lingchao; Huang, Chen; Rao, Shi

2017-12-01

There are two decisive factors for quantum correlations in reservoir engineering, but they are strongly reversely dependent on the atom-field nonlinearities. One is the squeezing parameter for the Bogoliubov modes-mediated collective interactions, while the other is the dissipative rates for the engineered collective dissipations. Exemplifying two-level atomic ensembles, we show that the moderate nonlinearities can compromise these two factors and thus enhance remarkably two-mode squeezing and entanglement of different spin atomic ensembles or different optical fields. This suggests that the moderate nonlinearities of the two-level systems are more advantageous for applications in quantum networks associated with reservoir engineering.

Dissipated energy and entropy production for an unconventional heat engine: the stepwise `circular cycle'

NASA Astrophysics Data System (ADS)

di Liberto, Francesco; Pastore, Raffaele; Peruggi, Fulvio

2011-05-01

When some entropy is transferred, by means of a reversible engine, from a hot heat source to a colder one, the maximum efficiency occurs, i.e. the maximum available work is obtained. Similarly, a reversible heat pumps transfer entropy from a cold heat source to a hotter one with the minimum expense of energy. In contrast, if we are faced with non-reversible devices, there is some lost work for heat engines, and some extra work for heat pumps. These quantities are both related to entropy production. The lost work, i.e. ? , is also called 'degraded energy' or 'energy unavailable to do work'. The extra work, i.e. ? , is the excess of work performed on the system in the irreversible process with respect to the reversible one (or the excess of heat given to the hotter source in the irreversible process). Both quantities are analysed in detail and are evaluated for a complex process, i.e. the stepwise circular cycle, which is similar to the stepwise Carnot cycle. The stepwise circular cycle is a cycle performed by means of N small weights, dw, which are first added and then removed from the piston of the vessel containing the gas or vice versa. The work performed by the gas can be found as the increase of the potential energy of the dw's. Each single dw is identified and its increase, i.e. its increase in potential energy, evaluated. In such a way it is found how the energy output of the cycle is distributed among the dw's. The size of the dw's affects entropy production and therefore the lost and extra work. The distribution of increases depends on the chosen removal process.

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.

PubMed

Emeny, Rebecca T; Baumert, Jens; Zannas, Anthony S; Kunze, Sonja; Wahl, Simone; Iurato, Stella; Arloth, Janine; Erhardt, Angelika; Balsevich, Georgia; Schmidt, Mathias V; Weber, Peter; Kretschmer, Anja; Pfeiffer, Liliane; Kruse, Johannes; Strauch, Konstantin; Roden, Michael; Herder, Christian; Koenig, Wolfgang; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Binder, Elisabeth B; Ladwig, Karl-Heinz

2018-01-01

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders.

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model

PubMed Central

Emeny, Rebecca T; Baumert, Jens; Zannas, Anthony S; Kunze, Sonja; Wahl, Simone; Iurato, Stella; Arloth, Janine; Erhardt, Angelika; Balsevich, Georgia; Schmidt, Mathias V; Weber, Peter; Kretschmer, Anja; Pfeiffer, Liliane; Kruse, Johannes; Strauch, Konstantin; Roden, Michael; Herder, Christian; Koenig, Wolfgang; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Binder, Elisabeth B; Ladwig, Karl-Heinz

2018-01-01

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders. PMID:28540928

Arabidopsis Ensemble Reverse-Engineered Gene Regulatory Network Discloses Interconnected Transcription Factors in Oxidative Stress[W

PubMed Central

Vermeirssen, Vanessa; De Clercq, Inge; Van Parys, Thomas; Van Breusegem, Frank; Van de Peer, Yves

2014-01-01

The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation. PMID:25549671

Arabidopsis ensemble reverse-engineered gene regulatory network discloses interconnected transcription factors in oxidative stress.

PubMed

Vermeirssen, Vanessa; De Clercq, Inge; Van Parys, Thomas; Van Breusegem, Frank; Van de Peer, Yves

2014-12-01

The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation. © 2014 American Society of Plant Biologists. All rights reserved.

A network-based dynamical ranking system for competitive sports

NASA Astrophysics Data System (ADS)

Motegi, Shun; Masuda, Naoki

2012-12-01

From the viewpoint of networks, a ranking system for players or teams in sports is equivalent to a centrality measure for sports networks, whereby a directed link represents the result of a single game. Previously proposed network-based ranking systems are derived from static networks, i.e., aggregation of the results of games over time. However, the score of a player (or team) fluctuates over time. Defeating a renowned player in the peak performance is intuitively more rewarding than defeating the same player in other periods. To account for this factor, we propose a dynamic variant of such a network-based ranking system and apply it to professional men's tennis data. We derive a set of linear online update equations for the score of each player. The proposed ranking system predicts the outcome of the future games with a higher accuracy than the static counterparts.

Fingerprinting with Wow

NASA Astrophysics Data System (ADS)

Yu, Eugene; Craver, Scott

2006-02-01

Wow, or time warping caused by speed fluctuations in analog audio equipment, provides a wealth of applications in watermarking. Very subtle temporal distortion has been used to defeat watermarks, and as components in watermarking systems. In the image domain, the analogous warping of an image's canvas has been used both to defeat watermarks and also proposed to prevent collusion attacks on fingerprinting systems. In this paper, we explore how subliminal levels of wow can be used for steganography and fingerprinting. We present both a low-bitrate robust solution and a higher-bitrate solution intended for steganographic communication. As already observed, such a fingerprinting algorithm naturally discourages collusion by averaging, owing to flanging effects when misaligned audio is averaged. Another advantage of warping is that even when imperceptible, it can be beyond the reach of compression algorithms. We use this opportunity to debunk the common misconception that steganography is impossible under "perfect compression."

How do emotional restrictions affect the use of humor? A behavior genetic analysis of alexithymia and humor styles.

PubMed

Atkinson, Breanna E; Lipton, Debra; Baughman, Holly M; Schermer, Julie A; Harris, Juliette; Vernon, Philip A

2015-04-01

This article reports the first behavioral genetic study of relationships between alexithymia and four styles of humor: affiliative, self-enhancing, self-defeating, and aggressive. A total of 509 MZ pairs and 264 DZ pairs of twins completed the Toronto Alexithymia Scale-20 (TAS-20) and the Humor Styles Questionnaire (HSQ). Consistent with our predictions, alexithymia correlated negatively with affiliative and self-enhancing humor and positively with self-defeating and aggressive humor. All but one of the 16 phenotypic correlations that we report are significant at the 0.01 level. Also consistent with our predictions, the phenotypic correlations between alexithymia and humor styles were primarily attributable to correlated genetic factors and to a lesser extent to correlated non-shared environmental factors. Correlated shared environmental factors had no significant effect. Implications and limitations of this study are discussed.

Climate effects of non-compliant Volkswagen diesel cars

NASA Astrophysics Data System (ADS)

Tanaka, Katsumasa; Lund, Marianne T.; Aamaas, Borgar; Berntsen, Terje

2018-04-01

On-road operations of Volkswagen light-duty diesel vehicles equipped with defeat devices cause emissions of NOx up to 40 times above emission standards. Higher on-road NOx emissions are a widespread problem not limited to Volkswagen vehicles, but the Volkswagen violations brought this issue under the spotlight. While several studies investigated the health impacts of high NOx emissions, the climatic impacts have not been quantified. Here we show that such diesel cars generate a larger warming on the time scale of several years but a smaller warming on the decadal time scale during actual on-road operations than in vehicle certification tests. The difference in longer-term warming levels, however, depends on underlying driving conditions. Furthermore, in the presence of defeat devices, the climatic advantage of ‘clean diesel’ cars over gasoline cars, in terms of global-mean temperature change, is in our view not necessarily the case.

California's Proposition 186: lessons from a single-payer health care reform ballot initiative campaign.

PubMed

Farey, K; Lingappa, V R

1996-01-01

Proposition 186 was an initiative on the November 1994 California ballot which proposed to establish a state single-payer health care program. Although Prop 186 was overwhelmingly defeated in the November 1994 election (73% No, 27% Yes), it accomplished many things. Model legislation was developed showing the feasibility of a specific single-payer program for California. It was placed on the ballot by an unprecedented volunteer signature-gathering effort and was the largest grassroots political campaign fund-raising effort in California history. A novel strategy for the discussion of complex issues through 1500 house parties was launched. Prop 186 was defeated by an insurance industry-led coalition with an anti-government message. Lessons for future efforts include increasing the size and duration of the grassroots organizing and educational effort, and decreasing reliance on conventional political campaign tactics and the mainstream media.

Civilian health during WWI and the causes of German defeat: a reexamination of the winter hypothesis.

PubMed

Voth, H J

1995-01-01

This paper is a reexamination of the Winter hypothesis, which holds that there was a marked difference in the development of civilian health during the First World War between the central powers and the Western allies. Ultimate success on the battlefield, according to Winter, required balancing the needs of the military with civilian demands; Germany lost because it failed to achieve such a balance. The resulting decline in health standards undermined the war effort and eventually led to defeat. This article proceeds in two steps. First, it demonstrates that Winter's data does not allow him to make a proper comparison between the two camps. Second, I argue that his hypothesis can be refuted once a truly comparable source is used--infant mortality rated. There is as yet no convincing evidence to suggest that the outcome of the First world War was determined by public health policy.

Tricking the guard: exploiting plant defense for disease susceptibility.

PubMed

Lorang, J; Kidarsa, T; Bradford, C S; Gilbert, B; Curtis, M; Tzeng, S-C; Maier, C S; Wolpert, T J

2012-11-02

Typically, pathogens deploy virulence effectors to disable defense. Plants defeat effectors with resistance proteins that guard effector targets. We found that a pathogen exploits a resistance protein by activating it to confer susceptibility in Arabidopsis. The guard mechanism of plant defense is recapitulated by interactions among victorin (an effector produced by the necrotrophic fungus Cochliobolus victoriae), TRX-h5 (a defense-associated thioredoxin), and LOV1 (an Arabidopsis susceptibility protein). In LOV1's absence, victorin inhibits TRX-h5, resulting in compromised defense but not disease by C. victoriae. In LOV1's presence, victorin binding to TRX-h5 activates LOV1 and elicits a resistance-like response that confers disease susceptibility. We propose that victorin is, or mimics, a conventional pathogen virulence effector that was defeated by LOV1 and confers virulence to C. victoriae solely because it incites defense.

Integrated two-cylinder liquid piston Stirling engine

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

Yang, Ning; Rickard, Robert; Pluckter, Kevin

2014-10-06

Heat engines utilizing the Stirling cycle may run on low temperature differentials with the capacity to function at high efficiency due to their near-reversible operation. However, current approaches to building Stirling engines are laborious and costly. Typically the components are assembled by hand and additional components require a corresponding increase in manufacturing complexity, akin to electronics before the integrated circuit. We present a simple and integrated approach to fabricating Stirling engines with precisely designed cylinders. We utilize computer aided design and one-step, planar machining to form all components of the engine. The engine utilizes liquid pistons and displacers to harnessmore » useful work from heat absorption and rejection. As a proof of principle of the integrated design, a two-cylinder engine is produced and characterized and liquid pumping is demonstrated.« less

Reverse engineering by design: using history to teach.

PubMed

Fagette, Paul

2013-01-01

Engineering students rarely have an opportunity to delve into the historic antecedents of design in their craft, and this is especially true for biomedical devices. The teaching emphasis is always on the new, the innovative, and the future. Even so, over the last decade, I have coupled a research agenda with engineering special projects into a successful format that allows young biomedical engineering students to understand aspects of their history and learn the complexities of design. There is value in having knowledge of historic engineering achievements, not just for an appreciation of these accomplishments but also for understanding exactly how engineers and clinicians of the day executed their feats-in other words, how the design process works. Ultimately, this particular educational odyssey confirms that history and engineering education are not only compatible but mutually supportive.

Integrated two-cylinder liquid piston Stirling engine

NASA Astrophysics Data System (ADS)

Yang, Ning; Rickard, Robert; Pluckter, Kevin; Sulchek, Todd

2014-10-01

Heat engines utilizing the Stirling cycle may run on low temperature differentials with the capacity to function at high efficiency due to their near-reversible operation. However, current approaches to building Stirling engines are laborious and costly. Typically the components are assembled by hand and additional components require a corresponding increase in manufacturing complexity, akin to electronics before the integrated circuit. We present a simple and integrated approach to fabricating Stirling engines with precisely designed cylinders. We utilize computer aided design and one-step, planar machining to form all components of the engine. The engine utilizes liquid pistons and displacers to harness useful work from heat absorption and rejection. As a proof of principle of the integrated design, a two-cylinder engine is produced and characterized and liquid pumping is demonstrated.