WorldWideScience

Sample records for dopamine system vulnerability

  1. The Impact of Exercise on the Vulnerability of Dopamine Neurons to Cell Death in Animal Models of Parkinson's Disease

    National Research Council Canada - National Science Library

    Zigmond, Michael J; Smith, Amanda; Liou, Anthony

    2006-01-01

    Parkinson's disease results in part from the loss of dopamine neurons. We hypothesize that exercise reduces the vulnerability of dopamine neurons to neurotoxin exposure, whereas stress increases vulnerability...

  2. Chronic treatment with extended release methylphenidate does not alter dopamine systems or increase vulnerability for cocaine self-administration: a study in nonhuman primates.

    Science.gov (United States)

    Gill, Kathryn E; Pierre, Peter J; Daunais, James; Bennett, Allyson J; Martelle, Susan; Gage, H Donald; Swanson, James M; Nader, Michael A; Porrino, Linda J

    2012-11-01

    Despite the widespread use of stimulant medications for the treatment of attention deficit hyperactivity disorder, few studies have addressed their long-term effects on the developing brain or susceptibility to drug use in adolescence. Here, we determined the effects of chronic methylphenidate (MPH) treatment on brain dopamine (DA) systems, developmental milestones, and later vulnerability to substance abuse in juvenile nonhuman primates. Male rhesus monkeys (approximately 30 months old) were treated daily with either a sustained release formulation of MPH or placebo (N=8 per group). Doses were titrated to achieve initial drug blood serum levels within the therapeutic range in children and adjusted throughout the study to maintain target levels. Growth, including measures of crown-rump length and weight, was assessed before and after 1 year of treatment and after 3-5 months washout. In addition, positron emission tomography scans were performed to quantify binding availability of D2/D3 receptors and dopamine transporters (DATs). Distribution volume ratios were calculated to quantify binding of [¹⁸F]fluoroclebopride (DA D2/D3) and [¹⁸F]-(+)-N-(4-fluorobenzyl)-2β-propanoyl-3β-(4-chlorophenyl)tropane (DAT). Chronic MPH did not differentially alter the course of weight gain or other measures of growth, nor did it influence DAT or D2/D3 receptor availability after 1 year of treatment. However, after washout, the D2/D3 receptor availability of MPH-treated animals did not continue to decline at the same rate as control animals. Acquisition of intravenous cocaine self-administration was examined by first substituting saline for food reinforcement and then cocaine doses (0.001-0.1 mg/kg per injection) in ascending order. Each dose was available for at least five consecutive sessions. The lowest dose of cocaine that maintained response rates significantly higher than saline-contingent rates was operationally defined as acquisition of cocaine reinforcement. There

  3. Dopamine

    International Nuclear Information System (INIS)

    Walters, L.

    1983-01-01

    Dopamine is an important neurotransmittor in the central nervous system. The physiological function of the peripheral dopamine receptors is unknown, but they are of therapeutic importance as dopamine is used to improve renal blood flow in shocked patients. There are 4 dopamine receptors. The classification of these dopamine receptors has been made possible by research with radiopharmaceuticals. Dopamine sensitive adenylate cyclase is an inherent part of the dopamine-1-receptor. Dopamine-1-receptors are stimulated by micromolar (physiological) concentrations of dopamine and inhibited by micromolar (supratherapeutic) concentrations of the antipsychotic drugs. The vascular effect of dopamine is mediated through the dopamine-1-receptors. Dopamine-2-receptors are responsible for the effect of dopamine at the mesolimbic, nigrostriatal and chemoreceptortrigger areas. It is activated by micromolar concentrations of dopamine and blocked by nanomolar (therapeutic) concentrations of the anti-psychotic drugs. Dopamine-3-receptors are activated by nanomolar concentrations of dopamine and inhibited by micromolar concentrations of the antipsychotic drugs. They occur on presynaptic nerve terminals and have a negative feedback effect on the liberation of dopamine, noradrenaline and serotonin. The dopamine-4-receptors are activated by nanomolar concentrations of dopamine. These are the only dopamine receptors that could be responsible for effects in the hypophysis as only nanomolar concentrations of dopamine occur there. These receptors are blocked by nanomolar concentrations of the antipsychotic drugs

  4. The Impact of Exercise on the Vulnerability of Dopamine Neurons to Cell Death in Animal Models of Parkinson's Disease

    National Research Council Canada - National Science Library

    Zpgmond, Michael J; Smith, Amanda; Liou, Anthony

    2007-01-01

    Parkinson's disease results in part from the loss of dopamine neurons. We hypothesize that exercise reduces the vulnerability of dopamine neurons to neurotoxin exposure, which is modulated by stress...

  5. The Impact of Exercise on the Vulnerability of Dopamine Neurons to Cell Death in Animal Models of Parkinson's Disease

    National Research Council Canada - National Science Library

    Zigmond, Michael J; Smith, Amanda

    2005-01-01

    Parkinson's disease (PD) results in part from the loss of dopamine (DA) neurons. We hypothesize that exercise reduces the vulnerability of DA neurons to neurotoxin exposure, whereas stress increases vulnerability...

  6. Vulnerability to glutamate toxicity of dopaminergic neurons is dependent on endogenous dopamine and MAPK activation.

    Science.gov (United States)

    Izumi, Yasuhiko; Yamamoto, Noriyuki; Matsuo, Takaaki; Wakita, Seiko; Takeuchi, Hiroki; Kume, Toshiaki; Katsuki, Hiroshi; Sawada, Hideyuki; Akaike, Akinori

    2009-07-01

    Dopaminergic neurons are more vulnerable than other types of neurons in cases of Parkinson disease and ischemic brain disease. An increasing amount of evidence suggests that endogenous dopamine plays a role in the vulnerability of dopaminergic neurons. Although glutamate toxicity contributes to the pathogenesis of these disorders, the sensitivity of dopaminergic neurons to glutamate toxicity has not been clarified. In this study, we demonstrated that dopaminergic neurons were preferentially affected by glutamate toxicity in rat mesencephalic cultures. Glutamate toxicity in dopaminergic neurons was blocked by inhibiting extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK. Furthermore, depletion of dopamine by alpha-methyl-dl-p-tyrosine methyl ester (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), protected dopaminergic neurons from the neurotoxicity. Exposure to glutamate facilitated phosphoryration of TH at Ser31 by ERK, which contributes to the increased TH activity. Inhibition of ERK had no additive effect on the protection offered by alpha-MT, whereas alpha-MT and c-jun N-terminal kinase or p38 MAPK inhibitors had additive effects and yielded full protection. These data suggest that endogenous dopamine is responsible for the vulnerability to glutamate toxicity of dopaminergic neurons and one of the mechanisms may be an enhancement of dopamine synthesis mediated by ERK.

  7. Computational systems analysis of dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Zhen Qi

    2008-06-01

    Full Text Available A prominent feature of Parkinson's disease (PD is the loss of dopamine in the striatum, and many therapeutic interventions for the disease are aimed at restoring dopamine signaling. Dopamine signaling includes the synthesis, storage, release, and recycling of dopamine in the presynaptic terminal and activation of pre- and post-synaptic receptors and various downstream signaling cascades. As an aid that might facilitate our understanding of dopamine dynamics in the pathogenesis and treatment in PD, we have begun to merge currently available information and expert knowledge regarding presynaptic dopamine homeostasis into a computational model, following the guidelines of biochemical systems theory. After subjecting our model to mathematical diagnosis and analysis, we made direct comparisons between model predictions and experimental observations and found that the model exhibited a high degree of predictive capacity with respect to genetic and pharmacological changes in gene expression or function. Our results suggest potential approaches to restoring the dopamine imbalance and the associated generation of oxidative stress. While the proposed model of dopamine metabolism is preliminary, future extensions and refinements may eventually serve as an in silico platform for prescreening potential therapeutics, identifying immediate side effects, screening for biomarkers, and assessing the impact of risk factors of the disease.

  8. The role of learning-related dopamine signals in addiction vulnerability.

    Science.gov (United States)

    Huys, Quentin J M; Tobler, Philippe N; Hasler, Gregor; Flagel, Shelly B

    2014-01-01

    Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction. © 2014 Elsevier B.V. All rights reserved.

  9. Vulnerability of damage-accumulating systems

    International Nuclear Information System (INIS)

    Lind, Niels C.

    1996-01-01

    Disastrous failures have shown that systems can be highly vulnerable. Quantified vulnerability can help designers and regulators to decide how much vulnerability is tolerable. Vulnerability of a system to a specified disturbance is defined as the ratio of the probability of failure of the disturbed system to the probability of failure of the undisturbed system. This vulnerability can be specialized to particular system types. It is adapted here to systems that are expected to deteriorate while in service due to processes such as fatigue, creep, corrosion, aging, neglect or insufficient maintenance. Application is illustrated by vulnerability to fatigue under constant and variable stress

  10. Dynamics of immune system vulnerabilities

    Science.gov (United States)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  11. Vulnerability

    NARCIS (Netherlands)

    Issa, Sahar; van der Molen, Irna; Stel, Nora

    2015-01-01

    This chapter reviews the literature on vulnerability. Together with Chapter 3, that offers a literature review specifically focused on resilience, it lays the conceptual foundations for the empirical chapters in this edited volume. Vulnerability symbolizes the susceptibility of a certain system to

  12. The evolution of dopamine systems in chordates

    Directory of Open Access Journals (Sweden)

    Kei eYamamoto

    2011-03-01

    Full Text Available Dopamine (DA neurotransmission in the central nervous system (CNS is found throughout chordates, and its emergence predates the divergence of chordates. Many of the molecular components of DA systems, such as biosynthetic enzymes, transporters and receptors, are shared with those of other monoamine systems, suggesting the common origin of these systems. In the mammalian CNS, the DA neurotransmitter systems are diversified and serve for visual and olfactory perception, sensory-motor programming, motivation, memory, emotion, and endocrine regulations. Some of the functions are conserved among different vertebrate groups, while others are not, and this is reflected in the anatomical aspects of DA systems in the forebrain and midbrain. Recent findings concerning a second tyrosine hydroxylase gene (TH2 revealed new populations of DA synthesizing cells, as evidenced in the periventricular hypothalamic zones of teleost fish. It is likely that the ancestor of vertebrates possessed TH2 DA-synthesizing cells, and the TH2 gene has been lost secondarily in placental mammals. All the vertebrates possess DA cells in the olfactory bulb, retina and in the diencephalon. Midbrain DA cells are abundant in amniotes while absent in some groups, e.g. teleosts. Studies of protochordate DA cells suggest that the diencephalic DA cells were present before the divergence of the chordate lineage. In contrast, the midbrain cell populations have probably emerged in the vertebrate lineage following the development of the midbrain-hindbrain boundary. The functional flexibility of the DA systems, and the evolvability provided by duplication of the corresponding genes permitted a large diversification of these systems. These features were instrumental in the adaptation of brain functions to the very variable way of life of vertebrates.

  13. Dopamine system: Manager of neural pathways

    Directory of Open Access Journals (Sweden)

    Simon eHong

    2013-12-01

    Full Text Available There are a growing number of roles that midbrain dopamine (DA neurons assume, such as, reward, aversion, alerting and vigor. Here I propose a theory that may be able to explain why the suggested functions of DA came about. It has been suggested that largely parallel cortico-basal ganglia-thalamo-cortico loops exist to control different aspects of behavior. I propose that (1 the midbrain DA system is organized in a similar manner, with different groups of DA neurons corresponding to these parallel neural pathways (NPs. The DA system can be viewed as the manager of these parallel NPs in that it recruits and activates only the task-relevant NPs when they are needed. It is likely that the functions of those NPs that have been consistently activated by the corresponding DA groups are facilitated. I also propose that (2 there are two levels of DA roles: the How and What roles. The How role is encoded in tonic and phasic DA neuron firing patterns and gives a directive to its target NP: how vigorously its function needs to be carried out. The tonic DA firing is to maintain a certain level of DA in the target NPs to support their expected behavioral and mental functions; it is only when a sudden unexpected boost or suppression of activity is required by the relevant target NP that DA neurons in the corresponding NP act in a phasic manner. The What role is the implementational aspect of the role of DA in the target NP, such as binding to D1 receptors to boost working memory. This What aspect of DA explains why DA seems to assume different functions depending on the region of the brain in which it is involved. In terms of the role of the lateral habenula (LHb, the LHb is expected to suppress maladaptive behaviors and mental processes by controlling the DA system. The demand-based smart management by the DA system may have given animals an edge in evolution with adaptive behaviors and a better survival rate in resource-scarce situations.

  14. Vulnerability of multiple-barrier systems

    International Nuclear Information System (INIS)

    Lind, N.C.

    1996-01-01

    'Vulnerability' is defined as the ratio of the probability of failure of a damaged system to the probability of failure of the undamaged system. This definition applies to all engineered systems and can be specialized to particular system types. Some disastrous failures (e.g., Chernobyl) have shown that systems can be highly vulnerable. open-quotes Defense in depthclose quotes is a powerful design principle, reducing vulnerability when the consequences of failure can be catastrophic. In the nuclear industry, defense in depth is widely used in radiation protection, reactor control, and shutdown systems. A multiple-barrier system is a simple example of a system that has defense in depth. The idea is that the system is not vulnerable. It cannot fail if one barrier fails because there is another to take its place. This idea is untenable in waste management, but a quantified vulnerability of a system can help owners, designers, and regulators decide how much defense in depth is desirable or enough. Many multiple-barrier systems can be modeled as systems of components physically in a series, each individually able to prevent failure. Components typically have bimodal distributions of the service time to failure, as illustrated by an example of application to a hypothetical nuclear fuel waste repository

  15. The dopamine motive system: implications for drug and food addiction.

    Science.gov (United States)

    Volkow, Nora D; Wise, Roy A; Baler, Ruben

    2017-11-16

    Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum. Cues that predict a reinforcing stimulus also modulate extrasynaptic dopamine concentrations, energizing motivation. Repeated administration of the reinforcer (drugs, energy-rich foods) generates conditioned associations between the reinforcer and the predicting cues, which is accompanied by downregulated dopaminergic response to other incentives and downregulated capacity for top-down self-regulation, facilitating the emergence of impulsive and compulsive responses to food or drug cues. Thus, dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding. Thus, interventions to rebalance the dopamine motive system might have therapeutic potential for obesity and addiction.

  16. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result...... in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...

  17. Genetic Variation in the Dopamine System Influences Intervention Outcome in Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Rochellys Diaz Heijtz

    2018-02-01

    Interpretation: Naturally occurring genetic variation in the dopamine system can influence treatment outcomes in children with cerebral palsy. A polygenic dopamine score might be valid for treatment outcome prediction and for designing individually tailored interventions for children with cerebral palsy.

  18. Vulnerability

    Science.gov (United States)

    Taback, I.

    1979-01-01

    The discussion of vulnerability begins with a description of some of the electrical characteristics of fibers before definiting how vulnerability calculations are done. The vulnerability results secured to date are presented. The discussion touches on post exposure vulnerability. After a description of some shock hazard work now underway, the discussion leads into a description of the planned effort and some preliminary conclusions are presented.

  19. Development and function of the midbrain dopamine system: what we know and what we need to

    OpenAIRE

    Bissonette, G. B.; Roesch, M. R.

    2015-01-01

    The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson’s disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, in...

  20. Study and development of retinal dopamine nervous system in experimental myopia

    International Nuclear Information System (INIS)

    Zhao Juan; Liu Xingdang

    2007-01-01

    Myopia is the most familiar ametropia. Animal experimental models include form deprivation myopia and defocus myopia. Experimental animals we often use are chicken and mammals. The retinal dopamine system and vision experience have close relations with the regulation of eyeball's growth after birth, while the change of dopamine transporter may reflect the change of dopamine in the synaptic cleft more directly. (authors)

  1. Intelligent Techniques for Power Systems Vulnerability Assessment

    Directory of Open Access Journals (Sweden)

    Mohamed A. El-Sharkawi

    2002-06-01

    Full Text Available With power grids considered national security matters, the reliable operation of the system is of top priority to utilities.  This concern is amplified by the utility’s deregulation, which increases the system’s openness while simultaneously decreasing the applied degree of control.  Vulnerability Assessment (VA deals with the power system’s ability to continue to provide service in case of an unforeseen catastrophic contingency.  Such contingencies may include unauthorized tripping, breaks in communication links, sabotage or intrusion by external agents, human errors, natural calamities and faults.  These contingencies could lead to a disruption of service to part or all of the system.  The service disruption is known as outage or blackout.  The paper outlines an approach by which feature extraction and boundary tracking can be implemented to achieve on line vulnerability assessment.

  2. Intelligent Techniques for Power Systems Vulnerability Assessment

    OpenAIRE

    Mohamed A. El-Sharkawi

    2002-01-01

    With power grids considered national security matters, the reliable operation of the system is of top priority to utilities.  This concern is amplified by the utility’s deregulation, which increases the system’s openness while simultaneously decreasing the applied degree of control.  Vulnerability Assessment (VA) deals with the power system’s ability to continue to provide service in case of an unforeseen catastrophic contingency.  Such contingencies may include unauthorized tripping, breaks ...

  3. Regenerative, Highly-Sensitive, Non-Enzymatic Dopamine Sensor and Impact of Different Buffer Systems in Dopamine Sensing

    Directory of Open Access Journals (Sweden)

    Saumya Joshi

    2018-01-01

    Full Text Available Carbon nanotube field-effect transistors are used extensively in ultra-sensitive biomolecule sensing applications. Along with high sensitivity, the possibility of regeneration is highly desired in bio-sensors. An important constituent of such bio-sensing systems is the buffer used to maintain pH and provide an ionic conducting medium, among its other properties. In this work, we demonstrate highly-sensitive regenerative dopamine sensors and the impact of varying buffer composition and type on the electrolyte gated field effect sensors. The role of the buffer system is an often ignored condition in the electrical characterization of sensors. Non-enzymatic dopamine sensors are fabricated and regenerated in hydrochloric acid (HCl solution. The sensors are finally measured against four different buffer solutions. The impact of the nature and chemical structure of buffer molecules on the dopamine sensors is shown, and the appropriate buffer systems are demonstrated.

  4. Individual differences in the propensity to approach signals vs goals promote different adaptations in the dopamine system of rats.

    Science.gov (United States)

    Flagel, Shelly B; Watson, Stanley J; Robinson, Terry E; Akil, Huda

    2007-04-01

    The way an individual responds to cues associated with rewards may be a key determinant of vulnerability to compulsive behavioral disorders. We studied individual differences in Pavlovian conditioned approach behavior and examined the expression of neurobiological markers associated with the dopaminergic system, the same neural system implicated in incentive motivational processes. Pavlovian autoshaping procedures consisted of the brief presentation of an illuminated retractable lever (conditioned stimulus) followed by the response-independent delivery of a food pellet (unconditioned stimulus), which lead to a Pavlovian conditioned response. In situ hybridization was performed on brains obtained either following the first or last (fifth) day of training. Two phenotypes emerged. Sign-trackers (ST) exhibited behavior that seemed to be largely controlled by the cue that signaled impending reward delivery; whereas goal-trackers (GT) preferentially approached the location where the reward was delivered. Following a single training session, ST showed greater expression of dopamine D1 receptor mRNA relative to GT. After 5 days of training, GT exhibited greater expression levels of tyrosine hydroxylase, dopamine transporter, and dopamine D2 receptor mRNA relative to ST. These findings suggest that the development of approach behavior towards signals vs goal leads to distinct adaptations in the dopamine system. The sign-tracker vs goal-tracker phenotype may prove to be a valuable animal model to investigate individual differences in the way incentive salience is attributed to environmental stimuli, which may contribute to the development of addiction and other compulsive behavioral disorders.

  5. SCADA system vulnerabilities to cyber attack

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, W. T. [Cyber Security Consulting (Canada)

    2004-10-01

    The susceptibility to terrorist attacks of computer-based supervisory control (SCADA) systems that are used to monitor and control water distribution systems, oil and gas pipelines and the electrical grid, is discussed. The discussion includes ways in which SCADA systems may be attacked and remedial actions that may be taken to reduce or eliminate the possibility of such attacks. Attacks may take the form of causing the system to generate false data to divert attention from impending system disasters, or commandeer the system to seriously disable it, or cause damage to the process or equipment being controlled by sending improper control commands. SCADA systems are also vulnerable to internal threats, either from an accidental action that results in damage, or an intentional action, as for example by a disgruntled employee, or ex-employee, usually by way of reprogramming an RTU or PLC by accessing the polling/communications circuit. Recent SCADA systems are much more susceptible to concerted cyber attacks because of the adoption of IT technologies and standards into the design of such systems. (Older systems are more likely to be unique designs, hence less susceptible to attack). As far as protection of SCADA systems is concerned, there are no technologies that would prevent a technologically sophisticated terrorist or disgruntled employee from doing major damage to the system, however, the IT world has developed a range of technologies for the protection of IT assets, and many of these same technologies can also be used to safeguard modern SCADA systems.

  6. Reward and aversion in a heterogeneous midbrain dopamine system.

    Science.gov (United States)

    Lammel, Stephan; Lim, Byung Kook; Malenka, Robert C

    2014-01-01

    The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Development and function of the midbrain dopamine system: what we know and what we need to.

    Science.gov (United States)

    Bissonette, G B; Roesch, M R

    2016-01-01

    The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  8. Effects of Pro-Gly-Pro tripeptide on the dopamine system.

    Science.gov (United States)

    Meshavkin, V K; Batishcheva, E Yu; Kost, N V; Sokolov, O Yu; Trufanova, A V; Samonina, G E

    2011-08-01

    Tripeptide Pro-Gly-Pro interacted with dopamine receptors in vitro and reduced behavioral manifestations of apomorphine-induced hyperfunction of the dopamine system in verticalization, stereotypy, and yawning tests. Presumably, the behavioral effects of Pro-Gly-Pro tripeptide were mediated through post- and presynaptic D(2)and D(3)receptors.

  9. Dopamine systems adaptation during acquisition and consolidation of a skill

    Directory of Open Access Journals (Sweden)

    Wolfgang H Sommer

    2014-11-01

    Full Text Available The striatum plays a key role in motor learning. Striatal function depends strongly on dopaminergic neurotransmission, but little is known about neuroadaptions of the dopamine system during striatal learning. Using an established task that allows differentiation between acquisition and consolidation of motor learning, we here investigate D1 and D2-like receptor binding and transcriptional levels after initial and long-term training of mice. We found profound reduction in D1 binding within the dorsomedial striatum (DMS after the first training session on the accelerated rotarod and a progressive reduction in D2-like binding within the dorsolateral striatum (DLS after extended training. Given that similar phase- and region-specific striatal neuroadaptations have been found also during learning of complex procedural tasks including habit formation and automatic responding, the here observed neurochemical alterations are important for our understanding of neuropsychiatric disorders that show a dysbalance in the function of striatal circuits, such as in addictive behaviours.

  10. A Survey of Satellite Communications System Vulnerabilities

    National Research Council Canada - National Science Library

    Steinberger, Jessica A

    2008-01-01

    The U.S. military's increasing reliance on commercial and military communications satellites to enable widely-dispersed, mobile forces to communicate makes these space assets increasingly vulnerable to attack by adversaries...

  11. Modulation of the mesolimbic dopamine system by leptin.

    Science.gov (United States)

    Opland, Darren M; Leinninger, Gina M; Myers, Martin G

    2010-09-02

    Nutritional status modulates many forms of reward-seeking behavior, with caloric restriction increasing the drive for drugs of abuse as well as for food. Understanding the interactions between the mesolimbic dopamine (DA) system (which mediates the incentive salience of natural and artificial rewards) and the neural and hormonal systems that sense and regulate energy balance is thus of significant importance. Leptin, which is produced by adipocytes in proportion to fat content as a hormonal signal of long-term energy stores, acts via its receptor (LepRb) on multiple populations of central nervous system neurons to modulate neural circuits in response to body energy stores. Leptin suppresses feeding and plays a central role in the control of energy balance. In addition to demonstrating that leptin modulates hypothalamic and brainstem circuits to promote satiety, recent work has begun to explore the mechanisms by which leptin influences the mesolimbic DA system and related behaviors. Indeed, leptin diminishes several measures of drug and food reward, and promotes a complex set of changes in the mesolimbic DA system. While many of the details remain to be worked out, several lines of evidence suggest that leptin regulates the mesolimbic DA system via multiple neural pathways and processes, and that distinct sets of LepRb neurons each modulate unique aspects of the mesolimbic DA system and behavior in response to leptin. 2010 Elsevier B.V. All rights reserved.

  12. Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation.

    Science.gov (United States)

    Ide, Soichiro; Takahashi, Takehiro; Takamatsu, Yukio; Uhl, George R; Niki, Hiroaki; Sora, Ichiro; Ikeda, Kazutaka

    2017-05-01

    Opioid and dopamine systems play crucial roles in reward. Similarities and differences in the neural mechanisms of reward that are mediated by these 2 systems have remained largely unknown. Thus, in the present study, we investigated the differences in reward function in both µ-opioid receptor knockout mice and dopamine transporter knockout mice, important molecules in the opioid and dopamine systems. Mice were implanted with electrodes into the right lateral hypothalamus (l hour). Mice were then trained to put their muzzle into the hole in the head-dipping chamber for intracranial electrical stimulation, and the influences of gene knockout were assessed. Significant differences are observed between opioid and dopamine systems in reward function. µ-Opioid receptor knockout mice exhibited enhanced intracranial electrical stimulation, which induced dopamine release. They also exhibited greater motility under conditions of "despair" in both the tail suspension test and water wheel test. In contrast, dopamine transporter knockout mice maintained intracranial electrical stimulation responding even when more active efforts were required to obtain the reward. The absence of µ-opioid receptor or dopamine transporter did not lead to the absence of intracranial electrical stimulation responsiveness but rather differentially altered it. The present results in µ-opioid receptor knockout mice are consistent with the suppressive involvement of µ-opioid receptors in both positive incentive motivation associated with intracranial electrical stimulation and negative incentive motivation associated with depressive states. In contrast, the results in dopamine transporter knockout mice are consistent with the involvement of dopamine transporters in positive incentive motivation, especially its persistence. Differences in intracranial electrical stimulation in µ-opioid receptor and dopamine transporter knockout mice underscore the multidimensional nature of reward. © The Author

  13. The hack attack - Increasing computer system awareness of vulnerability threats

    Science.gov (United States)

    Quann, John; Belford, Peter

    1987-01-01

    The paper discusses the issue of electronic vulnerability of computer based systems supporting NASA Goddard Space Flight Center (GSFC) by unauthorized users. To test the security of the system and increase security awareness, NYMA, Inc. employed computer 'hackers' to attempt to infiltrate the system(s) under controlled conditions. Penetration procedures, methods, and descriptions are detailed in the paper. The procedure increased the security consciousness of GSFC management to the electronic vulnerability of the system(s).

  14. Vulnerability Analysis of Urban Drainage Systems: Tree vs. Loop Networks

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2017-03-01

    Full Text Available Vulnerability analysis of urban drainage networks plays an important role in urban flood management. This study analyzes and compares the vulnerability of tree and loop systems under various rainfall events to structural failure represented by pipe blockage. Different pipe blockage scenarios, in which one of the pipes in an urban drainage network is assumed to be blocked individually, are constructed and their impacts on the network are simulated under different storm events. Furthermore, a vulnerability index is defined to measure the vulnerability of the drainage systems before and after the implementation of adaptation measures. The results obtained indicate that the tree systems have a relatively larger proportion of critical hydraulic pipes than the loop systems, thus the vulnerability of tree systems is substantially greater than that of the loop systems. Furthermore, the vulnerability index of tree systems is reduced after they are converted into a loop system with the implementation of adaptation measures. This paper provides an insight into the differences in the vulnerability of tree and loop systems, and provides more evidence for development of adaptation measures (e.g., tanks to reduce urban flooding.

  15. Monitoring the Vulnerability of Energy Supply System

    International Nuclear Information System (INIS)

    Gnansonounou, E.

    2006-01-01

    Due to the increasing complexity of the world evolution, the public decision makers, the energy supply industry and the consumers in industrialised countries are more and more sensitive to the vulnerability of energy supply. The emergence of new big consumer countries and the perspective of oil and gas depletion at the end of the current century raise the concerns about how to share fairly the remaining resources for the common and sustainable development of the mankind. Erratic energy prices discourage investment and delay the energy transition. Voluntary measures are needed mainly in industrialised countries in order to develop alternative and sustainable energy sources and to avoid world struggle for energy procurement. In this contribution a synthetic energy vulnerability index is defined for monitoring energy supply vulnerability. The proposed index is based on energy intensity, oil and gas import dependency, CO 2 content of primary energy supply, electricity supply vulnerability and non-diversity in transport fuels. The preliminary assessment of this synthetic index for selected industrialised countries provides promising results that need however further refinement.(author)

  16. Military Dependence on Commercial Satellite Communications Systems - Strength or Vulnerability

    National Research Council Canada - National Science Library

    Hook, Jack

    1999-01-01

    The military's growing dependence on commercial satellite communications systems will become a strength or vulnerability based on how well the right balance is achieved between commercial and military systems...

  17. Identifying Vulnerabilities and Hardening Attack Graphs for Networked Systems

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Sudip; Vullinati, Anil K.; Halappanavar, Mahantesh; Chatterjee, Samrat

    2016-09-15

    We investigate efficient security control methods for protecting against vulnerabilities in networked systems. A large number of interdependent vulnerabilities typically exist in the computing nodes of a cyber-system; as vulnerabilities get exploited, starting from low level ones, they open up the doors to more critical vulnerabilities. These cannot be understood just by a topological analysis of the network, and we use the attack graph abstraction of Dewri et al. to study these problems. In contrast to earlier approaches based on heuristics and evolutionary algorithms, we study rigorous methods for quantifying the inherent vulnerability and hardening cost for the system. We develop algorithms with provable approximation guarantees, and evaluate them for real and synthetic attack graphs.

  18. Individual differences and vulnerability to drug addiction: a focus on the endocannabinoid system.

    Science.gov (United States)

    Sagheddu, Claudia; Melis, Miriam

    2015-01-01

    Vulnerability to drug addiction depends upon the interactions between the biological makeup of the individual, the environment, and age. These interactions are complex and difficult to tease apart. Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure. In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) has been considered a putative protective and a risk factor, respectively, that can influence one's susceptibility to continued drug abuse as well as the transition to addiction. This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons. Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle. In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented. Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.

  19. Characterization of D1 dopamine receptors in the central nervous system

    International Nuclear Information System (INIS)

    Hess, E.J.

    1987-01-01

    Several lines of evidence suggest an association of central nervous system dopaminergic systems in the etiology of the schizophrenia. Interest in the role of D 1 dopamine receptors has revived with the advent of selective drugs for this dopamine receptor, particularly the D 1 dopamine receptor antagonists, SCH23390. [ 3 H]SCH23390 represents a superior radioligand for labeling the two-state striatal D 1 dopamine receptor in that its high percent specific binding makes it especially suitable for detailed mechanistic studies of this receptor. Striatal D 1 dopamine receptors have been shown to mediate the stimulation of adenylate cyclase activity via a guanine nucleotide regulatory subunit. Forskolin acts in a synergistic manner with dopamine agonists, guanine nucleotides or sodium fluoride to potentiate the stimulation of rat striatal adenylate cyclase activity mediated by these reagents. By using the aforementioned reagents and the irreversible receptor modifying reagent N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroquinoline, we demonstrated that the D 1 dopamine receptor population in rat striatum is not a stoichiometrically-limiting factor in agonist stimulation of adenylate cyclase activity

  20. Measurements, in vivo, of parameters of the dopamine system

    International Nuclear Information System (INIS)

    Friedman, A.M.; DeJesus, O.T.; Dinerstein, R.; Revenaugh, J.

    1983-01-01

    This paper discusses methods of measuring important parameters of the dopamine system in the living animal by use of PET techniques. One primary concern is the density and binding affinity of post-synaptic neuroreceptors. A second concern is the activity of neurons. In vivo, this is generally related to the turnover of neurotransmitter and can also be related to the uptake of precursor compounds by the neurons. If the transmitter and neuroleptic compound compete for the same binding sites (on the receptor molecule) these two effects are interwoven and are not easily isolated. It appears that the movement of neuroleptic drugs from the brain is slow enough to allow equilibrium to be maintained between ligand and receptor, especially after some time for the initial washout and translocation in the brain. To test the consequences of equilibrium binding and the possible use of the model for measurement of receptor densities by emission tomography we have modified Clark's equilibrium model of ligand binding. In this note we will describe the solutions of the equations and some comparisons of the predictions of the model with data, as well as its application to tomographic measurements

  1. Analysis on Single Point Vulnerabilities of Plant Control System

    International Nuclear Information System (INIS)

    Chi, Moon Goo; Lee, Eun Chan; Bae, Yeon Kyoung

    2011-01-01

    The Plant Control System (PCS) is a system that controls pumps, valves, dampers, etc. in nuclear power plants with an OPR-1000 design. When there is a failure or spurious actuation of the critical components in the PCS, it can result in unexpected plant trips or transients. From this viewpoint, single point vulnerabilities are evaluated in detail using failure mode effect analyses (FMEA) and fault tree analyses (FTA). This evaluation demonstrates that the PCS has many vulnerable components and the analysis results are provided for OPR-1000 plants for reliability improvements that can reduce their vulnerabilities

  2. Analysis on Single Point Vulnerabilities of Plant Control System

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Moon Goo; Lee, Eun Chan; Bae, Yeon Kyoung [Korea Hydro and Nuclear Power Co., Daejeon (Korea, Republic of)

    2011-08-15

    The Plant Control System (PCS) is a system that controls pumps, valves, dampers, etc. in nuclear power plants with an OPR-1000 design. When there is a failure or spurious actuation of the critical components in the PCS, it can result in unexpected plant trips or transients. From this viewpoint, single point vulnerabilities are evaluated in detail using failure mode effect analyses (FMEA) and fault tree analyses (FTA). This evaluation demonstrates that the PCS has many vulnerable components and the analysis results are provided for OPR-1000 plants for reliability improvements that can reduce their vulnerabilities.

  3. Effective vulnerability assessments for physical security devices, systems, and programs

    International Nuclear Information System (INIS)

    Johnston, R.G.; Garcia, A.R.E.

    2002-01-01

    Full text: The efficacy of devices, systems, and programs used for physical security depend critically on having periodic and effective vulnerability assessments. Effective vulnerability assessments, in turn, require certain conditions and attributes. These include: a proper understanding of their purpose; not confusing vulnerability assessments with other kinds of metrics, analyses, tests, and security exercises; the view that vulnerabilities are inevitable, and that finding them is good news (since they can then be mitigated), not bad news; rejection of findings of no vulnerabilities; avoidance of mere 'compliance mode' rubber stamping; the use of the proper outside, independent, imaginative personnel; psychologically predisposed to finding and demonstrating problems; the absence of conflicts of interest; no unrealistic constraints on the possible attack tools, procedures, personnel, or strategies; efforts to not just find and demonstrate vulnerabilities, but also to suggest possible countermeasures; proper context; input and buy-in from ALL facility security personnel, especially low-level personnel; emphasis on the simplest, most relevant attacks first; no underestimation of potential adversaries; consideration of fault analysis attacks; awareness of Rohrbach's Maxim and Shannon's Maxim. In addition to these factors, we will cover some of the complex issues and problems associated with the design of vulnerability assessments. There will also be suggestions on how to conduct effective vulnerability assessments on a severely limited budget. We will conclude with a discussion of both conventional and unconventional ways of reporting results. (author)

  4. Antidepressant activity of curcumin: involvement of serotonin and dopamine system.

    Science.gov (United States)

    Kulkarni, Shrinivas K; Bhutani, Mohit Kumar; Bishnoi, Mahendra

    2008-12-01

    Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

  5. Assessing Financial System Vulnerabilities: An Early Warning Approach

    OpenAIRE

    Gurnain Pasricha; Tom Roberts; Ian Christensen; Brad Howell

    2013-01-01

    This article focuses on a quantitative method to identify financial system vulnerabilities, specifically, an imbalance indicator model (IIM) and its application to Canada. An IIM identifies potential vulnerabilities in a financial system by comparing current economic and financial data with data from periods leading up to past episodes of financial stress. It complements other sources of information - including market intelligence and regular monitoring of the economy - that policy-makers use...

  6. Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation.

    Science.gov (United States)

    Beeler, Jeff A; Faust, Rudolf P; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

    2016-06-01

    The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. The KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. LOW DOPAMINE D2 RECEPTOR INCREASES VULNERABILITY TO OBESITY VIA REDUCED PHYSICAL ACTIVITY NOT INCREASED APPETITIVE MOTIVATION

    Science.gov (United States)

    Beeler, Jeff A.; Faust, Rudolf P.; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

    2015-01-01

    Background The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a “reward deficiency” and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. Methods We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. Results The KD mice did not gain more weight or show increased appetitive motivation compared to wild-type (WT) in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than WT, obtaining no protective benefit from exercise opportunities. Conclusions These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. PMID:26281715

  8. Dopamine transporters govern diurnal variation in extracellular dopamine tone

    OpenAIRE

    Ferris, Mark J.; España, Rodrigo A.; Locke, Jason L.; Konstantopoulos, Joanne K.; Rose, Jamie H.; Chen, Rong; Jones, Sara R.

    2014-01-01

    The mechanism for diurnal (i.e., light/dark) oscillations in extracellular dopamine tone in mesolimbic and nigrostriatal systems is unknown. This is because, unlike other neurotransmitter systems, variation in dopamine tone does not correlate with variation in dopamine cell firing. The current research pinpoints the dopamine transporter as a critical governor of diurnal variation in both extracellular dopamine tone and the intracellular availability of releasable dopamine. These data describe...

  9. [Neurotensin-like oligopeptides as potential antipsychotics: effect on dopamine system].

    Science.gov (United States)

    Kost, N V; Meshavkin, V K; Batishcheva, E Iu; Sokolov, O Iu; Andreeva, L A; Miasoedov, N F

    2011-01-01

    According to published data, peptide neurotensin is considered as endogenous antipsychotic agent. A series of oligopeptides have been synthesized based on the proposed active center of neurotensin. These oligopeptides (called neurotensin-like peptides, NLPs) have been studied on behavioral models, in which the functional state of the dopamine system of animals was modified by apomorphine injections. The results of verticalization, stereotypy, and yawning tests revealed NLPs that behave as antagonists of dopamine receptors. Radioligand analysis showed that these peptides compete for specific binding to these receptors with sulpiride, which is a D2-type selective antagonist of dopamine receptors. The high degree of NLPs efficiency manifested in the behavioral tests and radioligand analysis suggests that the their antipsychotic action can be mediated by dopamine receptors.

  10. Structural vulnerability in transmission systems: Cases of Colombia and Spain

    International Nuclear Information System (INIS)

    Correa, Gabriel J.; Yusta, José M.

    2014-01-01

    Highlights: • Vulnerability analysis of transmission electric systems in Colombia and Spain. • Based on scale-free graph statistic indexes. • Evaluating both current conditions and expansion plans of infrastructures. • Comparison of random error and deliberate attack tolerance evaluation. - Abstract: In this paper the authors apply methodological strategies for the structural vulnerability assessment in high voltage power networks based upon the combination of power flow models and scale-free graph statistic indexes. Thus, it is possible to study risk scenarios based on events that may trigger cascading failures within a power system. The usefulness of graph theory techniques has been validated on previous works of the authors, and may be applied in analysis of the vulnerability of different power electric networks. A case study for vulnerability analysis is carried out through methodologies that allow comparison on random error and deliberate attack tolerance evaluation in transmission electric systems from countries like Colombia and Spain. Such vulnerability assessment methodology takes into account the current conditions of the power networks (base case), as well as the impact of expansion plans into infrastructures as defined by their governments. Consequently, the authors show the advantage on the use of graph theory based techniques for vulnerability analysis of electrical power systems

  11. Quantitative Vulnerability Assessment of Cyber Security for Distribution Automation Systems

    Directory of Open Access Journals (Sweden)

    Xiaming Ye

    2015-06-01

    Full Text Available The distribution automation system (DAS is vulnerable to cyber-attacks due to the widespread use of terminal devices and standard communication protocols. On account of the cost of defense, it is impossible to ensure the security of every device in the DAS. Given this background, a novel quantitative vulnerability assessment model of cyber security for DAS is developed in this paper. In the assessment model, the potential physical consequences of cyber-attacks are analyzed from two levels: terminal device level and control center server level. Then, the attack process is modeled based on game theory and the relationships among different vulnerabilities are analyzed by introducing a vulnerability adjacency matrix. Finally, the application process of the proposed methodology is illustrated through a case study based on bus 2 of the Roy Billinton Test System (RBTS. The results demonstrate the reasonability and effectiveness of the proposed methodology.

  12. Vulnerability Management for an Enterprise Resource Planning System

    Science.gov (United States)

    Goel, Shivani; Kiran, Ravi; Garg, Deepak

    2012-09-01

    Enterprise resource planning (ERP) systems are commonly used in technical educational institutions(TEIs). ERP systems should continue providing services to its users irrespective of the level of failure. There could be many types of failures in the ERP systems. There are different types of measures or characteristics that can be defined for ERP systems to handle the levels of failure. Here in this paper, various types of failure levels are identified along with various characteristics which are concerned with those failures. The relation between all these is summarized. The disruptions causing vulnerabilities in TEIs are identified .A vulnerability management cycle has been suggested along with many commercial and open source vulnerability management tools. The paper also highlights the importance of resiliency in ERP systems in TEIs.

  13. Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism.

    Science.gov (United States)

    Ball, Kevin T; Stone, Eric; Best, Olivia; Collins, Tyler; Edson, Hunter; Hagan, Erin; Nardini, Salvatore; Neuciler, Phelan; Smolinsky, Michael; Tosh, Lindsay; Woodlen, Kristin

    2018-06-01

    A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers. We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure. A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 μg/kg; i.p.), a dopamine D 1 -like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement. Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D 1 -like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. APRESS: apical regulatory super system, serotonin, and dopamine interaction

    Directory of Open Access Journals (Sweden)

    Hinz M

    2011-08-01

    Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USABackground: The monoamines serotonin and dopamine are known to exist in two separate states: the endogenous state and the competitive inhibition state. The presence of the competitive inhibition state has been known to science for many years, but from a functional standpoint it has been noted in the literature as being "meaningless."Methods: A large database of monoamine transporter response to amino acid precursor administration variations with clinical outcomes was accumulated. In the process, a new organic cation transporter (OCT model has been published, and OCT functional status determination along with amino acid precursor manipulation methods have been invented and refined.Results: Methodology was developed whereby manipulation of the OCT, in the competitive inhibition state, is carried out in a predictable manner. This, in turn, has disproved the long-held assertion that the monoamine competitive inhibition state is functionally meaningless.Conclusion: The most significant aspect of this paper is the documentation of newly recognized relationships between serotonin and dopamine. When transport of serotonin and dopamine are both in the competitive inhibition state, manipulation of the concentrations of one will lead to predictable changes in concentrations of the other. From a functional standpoint, processes regulated and controlled by changes to only serotonin can now be controlled by changes to dopamine, and vice versa, in a predictable manner.Keywords: catecholamine, monoamine, competitive inhibition state

  15. Formal Vulnerability Assessment of a maritime transportation system

    International Nuclear Information System (INIS)

    Berle, Oyvind; Asbjornslett, Bjorn Egil; Rice, James B.

    2011-01-01

    World trade increasingly relies on longer, larger and more complex supply chains, where maritime transportation is a vital backbone of such operations. Long and complex supply chain systems are more prone to being vulnerable, though through reviews, no specific methods have been found to assess vulnerabilities of a maritime transportation system. Most existing supply chain risk assessment frameworks require risks to be foreseen to be mitigated, rather than giving transportation systems the ability to cope with unforeseen threats and hazards. In assessing cost-efficiency, societal vulnerability versus industrial cost of measures should be included. This conceptual paper presents a structured Formal Vulnerability Assessment (FVA) methodology, seeking to transfer the safety-oriented Formal Safety Assessment (FSA) framework into the domain of maritime supply chain vulnerability. To do so, the following two alterations are made: (1) The focus of the assessment is defined to ensure the ability of the transportation to serve as a throughput mechanism of goods, and to survive and recover from disruptive events. (2) To cope with low-frequency high-impact disruptive scenarios that were not necessarily foreseen, two parallel tracks of risk assessments need to be pursued-the cause-focused risk assessment as in the FSA, and a consequence-focused failure mode approach.

  16. Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain.

    Science.gov (United States)

    Hungen, K V; Roberts, S; Hill, D F

    1975-08-22

    Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and

  17. Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

    Science.gov (United States)

    Fricchione, Gregory; Stefano, George B

    2005-05-01

    Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

  18. Autoradiographic localization of mu and delta opioid receptors in the mesocorticolimbic dopamine system

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P. Jr.

    1989-01-01

    In vitro autoradiographic techniques were coupled with selective chemical lesions of the A10 dopamine cells and intrinsic perikarya of the region to delineate the anatomical localization of mu and delta opioid receptors, as well as, neurotensin receptors. Mu opioid receptors were labeled with {sup 125}I-DAGO. Delta receptors were labeled with {sup 125}I-DPDPE. Neurotensin receptors were labeled with {sup 125}I-NT3. Unilateral lesions of the dopamine perikarya were produced by injections of 6-OHDA administered in the ventral mesencephalon. Unilateral lesions of intrinsic perikarya were induced by injections of quinolinic acid in to the A10 dopamine cell region. Unilateral lesions produced with 6-OHDA resulted in the loss of neurotensin receptors in the A10 region and within the terminal fields. Mu opioid receptors were unaffected by this treatment, but delta opioid receptors increased in the contralateral striatum and nucleus accumbens following 6-OHDA administration. Quinolinic acid produced a reduction of mu opioid receptors within the A10 region with a concomitant reduction in neurotensin receptors in both the cell body region and terminal fields. These results are consistent with a variety of biochemical and behavioral data which suggest the indirect modulation of dopamine transmission by the opioids. In contrast these results strongly indicate a direct modulation of the mesolimbic dopamine system by neurotensin.

  19. Neuroimaging of the Dopamine/Reward System in Adolescent Drug Use

    Science.gov (United States)

    Ernst, Monique; Luciana, Monica

    2015-01-01

    Adolescence is characterized by heightened risk-taking, including substance misuse. These behavioral patterns are influenced by ontogenic changes in neurotransmitter systems, particularly the dopamine system, which is fundamentally involved in the neural coding of reward and motivated approach behavior. During adolescence, this system evidences a peak in activity. At the same time, the dopamine system is neuroplastically altered by substance abuse, impacting subsequent function. Here, we describe properties of the dopamine system that change with typical adolescent development and that are altered with substance abuse. Much of this work has been gleaned from animal models due to limitations in measuring dopamine in pediatric samples. Structural and functional neuroimaging techniques have been used to examine structures that are heavily DA-innervated; they measure morphological and functional changes with age and with drug exposure. Presenting marijuana abuse as an exemplar, we consider recent findings that support an adolescent peak in DA-driven reward-seeking behavior and related deviations in motivational systems that are associated with marijuana abuse/dependence. Clinicians are advised that (1) chronic adolescent marijuana use may lead to deficiencies in incentive motivation, (2) that this state is due to marijuana’s interactions with the developing DA system, and (3) that treatment strategies should be directed to remediating resultant deficiencies in goal-directed activity. PMID:26095977

  20. The Vulnerability Assessment Code for Physical Protection System

    International Nuclear Information System (INIS)

    Jang, Sung Soon; Yoo, Ho Sik

    2007-01-01

    To neutralize the increasing terror threats, nuclear facilities have strong physical protection system (PPS). PPS includes detectors, door locks, fences, regular guard patrols, and a hot line to a nearest military force. To design an efficient PPS and to fully operate it, vulnerability assessment process is required. Evaluating PPS of a nuclear facility is complicate process and, hence, several assessment codes have been developed. The estimation of adversary sequence interruption (EASI) code analyzes vulnerability along a single intrusion path. To evaluate many paths to a valuable asset in an actual facility, the systematic analysis of vulnerability to intrusion (SAVI) code was developed. KAERI improved SAVI and made the Korean analysis of vulnerability to intrusion (KAVI) code. Existing codes (SAVI and KAVI) have limitations in representing the distance of a facility because they use the simplified model of a PPS called adversary sequence diagram. In adversary sequence diagram the position of doors, sensors and fences is described just as the locating area. Thus, the distance between elements is inaccurate and we cannot reflect the range effect of sensors. In this abstract, we suggest accurate and intuitive vulnerability assessment based on raster map modeling of PPS. The raster map of PPS accurately represents the relative position of elements and, thus, the range effect of sensor can be easily incorporable. Most importantly, the raster map is easy to understand

  1. Vulnerability Assessment of Water Supply Systems: Status, Gaps and Opportunities

    Science.gov (United States)

    Wheater, H. S.

    2015-12-01

    Conventional frameworks for assessing the impacts of climate change on water resource systems use cascades of climate and hydrological models to provide 'top-down' projections of future water availability, but these are subject to high uncertainty and are model and scenario-specific. Hence there has been recent interest in 'bottom-up' frameworks, which aim to evaluate system vulnerability to change in the context of possible future climate and/or hydrological conditions. Such vulnerability assessments are generic, and can be combined with updated information from top-down assessments as they become available. While some vulnerability methods use hydrological models to estimate water availability, fully bottom-up schemes have recently been proposed that directly map system vulnerability as a function of feasible changes in water supply characteristics. These use stochastic algorithms, based on reconstruction or reshuffling methods, by which multiple water supply realizations can be generated under feasible ranges of change in water supply conditions. The paper reports recent successes, and points to areas of future improvement. Advances in stochastic modeling and optimization can address some technical limitations in flow reconstruction, while various data mining and system identification techniques can provide possibilities to better condition realizations for consistency with top-down scenarios. Finally, we show that probabilistic and Bayesian frameworks together can provide a potential basis to combine information obtained from fully bottom-up analyses with projections available from climate and/or hydrological models in a fully integrated risk assessment framework for deep uncertainty.

  2. Integration of vulnerable road users in cooperative ITS systems

    NARCIS (Netherlands)

    Scholliers, J.; Sambeek, M. van; Moerman, K.

    2017-01-01

    Introduction: This paper describes the development of an architecture for the integration of Vulnerable Road Users (VRUs), i.e. pedestrians, cyclists and powered two-wheelers (PTWs) in Cooperative ITS (C-ITS) systems, and the requirements for VRU devices. Methods: This paper starts with a literature

  3. Mitigations for Security Vulnerabilities Found in Control System Networks

    Energy Technology Data Exchange (ETDEWEB)

    Trent D. Nelson

    2006-05-01

    Industry is aware of the need for Control System (CS) security, but in on-site assessments, Idaho National Laboratory (INL) has observed that security procedures and devices are not consistently and effectively implemented. The Department of Homeland Security (DHS), National Cyber Security Division (NCSD), established the Control Systems Security Center (CSSC) at INL to help industry and government improve the security of the CSs used in the nation's critical infrastructures. One of the main CSSC objectives is to identify control system vulnerabilities and develop effective mitigations for them. This paper discusses common problems and vulnerabilities seen in on-site CS assessments and suggests mitigation strategies to provide asset owners with the information they need to better protect their systems from common security flows.

  4. Polymorphisms in Dopamine System Genes Are Associated with Individual Differences in Attention in Infancy

    Science.gov (United States)

    Holmboe, Karla; Nemoda, Zsofia; Fearon, R. M. Pasco; Csibra, Gergely; Sasvari-Szekely, Maria; Johnson, Mark H.

    2010-01-01

    Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the…

  5. Vulnerability analysis for a drought Early Warning System

    Science.gov (United States)

    Angeluccetti, Irene; Demarchi, Alessandro; Perez, Francesca

    2014-05-01

    Early Warning Systems (EWS) for drought are often based on risk models that do not, or marginally, take into account the vulnerability factor. The multifaceted nature of drought (hydrological, meteorological, and agricultural) is source of coexistence for different ways to measure this phenomenon and its effects. The latter, together with the complexity of impacts generated by this hazard, causes the current underdevelopment of drought EWS compared to other hazards. In Least Developed Countries, where drought events causes the highest numbers of affected people, the importance of correct monitoring and forecasting is considered essential. Existing early warning and monitoring systems for drought produced at different geographic levels, provide only in a few cases an actual spatial model that tries to describe the cause-effect link between where the hazard is detected and where impacts occur. Integrate vulnerability information in such systems would permit to better estimate affected zones and livelihoods, improving the effectiveness of produced hazard-related datasets and maps. In fact, the need of simplification and, in general, of a direct applicability of scientific outputs is still a matter of concern for field experts and early warning products end-users. Even if the surplus of hazard related information produced right after catastrophic events has, in some cases, led to the creation of specific data-sharing platforms, the conveyed meaning and usefulness of each product has not yet been addressed. The present work is an attempt to fill this gap which is still an open issue for the scientific community as well as for the humanitarian aid world. The study aims at conceiving a simplified vulnerability model to embed into an existing EWS for drought, which is based on the monitoring of vegetation phenological parameters and the Standardized Precipitation Index, both produced using free satellite derived datasets. The proposed vulnerability model includes (i) a

  6. Vulnerability of ecological systems for nuclear war climatic consequences

    International Nuclear Information System (INIS)

    Kharuehll, M.; Khatchinson, T.; Kropper, U.; Kharuehll, K.

    1988-01-01

    Vulnerability of ecological systems of Northern hemisphere (terrestrial, aquatic and tropical) as well as Southern one in relation to climatic changes following large nuclear war is considered. When analyzing potential sensitivity of ecological systems to climatic changes, possible consequences are considered for different stress categories under various war scenarios. The above-mentioned stresses correspond to those adopted in published work by Pittok and others. To estimate the less important climatic disturbances a few additional computer-simulated models are developed

  7. Juvenile hormone-dopamine systems for the promotion of flight activity in males of the large carpenter bee Xylocopa appendiculata

    Science.gov (United States)

    Sasaki, Ken; Nagao, Takashi

    2013-12-01

    The reproductive roles of dopamine and dopamine regulation systems are known in social hymenopterans, but the knowledge on the regulation systems in solitary species is still needed. To test the possibility that juvenile hormone (JH) and brain dopamine interact to trigger territorial flight behavior in males of a solitary bee species, the effects on biogenic amines of JH analog treatments and behavioral assays with dopamine injections in males of the large carpenter bee Xylocopa appendiculata were quantified. Brain dopamine levels were significantly higher in methoprene-treated males than in control males 4 days after treatment, but were not significantly different after 7 days. Brain octopamine and serotonin levels did not differ between methoprene-treated and control males at 4 and 7 days after treatment. Injection of dopamine caused significantly higher locomotor activities and a shorter duration for flight initiation in experimental versus control males. These results suggest that brain dopamine can be regulated by JH and enhances flight activities in males. The JH-dopamine system in males of this solitary bee species is similar to that of males of the highly eusocial honeybee Apis mellifera.

  8. Dopamine modulates reward system activity during subconscious processing of sexual stimuli.

    Science.gov (United States)

    Oei, Nicole Y L; Rombouts, Serge Arb; Soeter, Roelof P; van Gerven, Joop M; Both, Stephanie

    2012-06-01

    Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive-compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the 'reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate 'wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.

  9. Vulnerability assessment and mitigation for the Chinese railway system under floods

    International Nuclear Information System (INIS)

    Hong, Liu; Ouyang, Min; Peeta, Srinivas; He, Xiaozheng; Yan, Yongze

    2015-01-01

    The economy of China and the travel needs of its citizens depend significantly on the continuous and reliable services provided by its railway system. However, this system is subject to frequent natural hazards, such as floods, earthquakes, and debris flow. A mechanism to assess the railway system vulnerability under these hazards and the design of effective vulnerability mitigation strategies are essential to the reliable functioning of the railway system. This article proposes a comprehensive methodology to quantitatively assess the railway system vulnerability under floods using historical data and GIS technology. The proposed methodology includes a network representation of the railway system, the generation of flood event scenarios, a method to estimate railway link vulnerability, and a quantitative vulnerability value computation approach. The railway system vulnerability is evaluated in terms of its service disruption related to the number of interrupted trains and the durations of interruption. A maintenance strategy to mitigate vulnerability is proposed that simultaneously considers link vulnerability and number of trains using it. Numerical experiments show that the flood-induced vulnerability of the proposed representation of the Chinese railway system reaches its maximum monthly value in July, and the proposed vulnerability mitigation strategy is more effective compared to other strategies. - Highlights: • We propose a methodology to assess flood-induced railway system vulnerability. • Railway system vulnerability is evaluated in terms of its service disruption. • Chinese railway system reaches its maximum monthly vulnerability in July. • We propose an effective maintenance strategy considering link vulnerability and burden

  10. Dynamic vulnerability assessment and intelligent control for sustainable power systems

    CERN Document Server

    Gonzalez-Longatt, Francisco

    2018-01-01

    Identifying, assessing, and mitigating electric power grid vulnerabilities is a growing focus in short-term operational planning of power systems. Through illustrated application, this important guide surveys state-of-the-art methodologies for the assessment and enhancement of power system security in short-term operational planning and real-time operation. The methodologies employ advanced methods from probabilistic theory, data mining, artificial intelligence, and optimization, to provide knowledge-based support for monitoring, control (preventive and corrective), and decision making tasks. Key features: Introduces behavioural recognition in wide-area monitoring and security constrained optimal power flow for intelligent control and protection and optimal grid management. Provides in-depth understanding of risk-based reliability and security assessment, dynamic vulnerability as essment methods, supported by the underpinning mathematics. Develops expertise in mitigation techniques using intelligent protect...

  11. Groundwater vulnerability mapping in Guadalajara aquifers system (Western Mexico)

    Science.gov (United States)

    Rizo-Decelis, L. David; Marín, Ana I.; Andreo, Bartolomé

    2016-04-01

    Groundwater vulnerability mapping is a practical tool to implement strategies for land-use planning and sustainable socioeconomic development coherent with groundwater protection. The objective of vulnerability mapping is to identify the most vulnerable zones of catchment areas and to provide criteria for protecting the groundwater used for drinking water supply. The delineation of protection zones in fractured aquifers is a challenging task due to the heterogeneity and anisotropy of hydraulic conductivities, which makes difficult prediction of groundwater flow organization and flow velocities. Different methods of intrinsic groundwater vulnerability mapping were applied in the Atemajac-Toluquilla groundwater body, an aquifers system that covers around 1300 km2. The aquifer supplies the 30% of urban water resources of the metropolitan area of Guadalajara (Mexico), where over 4.6 million people reside. Study area is located in a complex neotectonic active volcanic region in the Santiago River Basin (Western Mexico), which influences the aquifer system underneath the city. Previous works have defined the flow dynamics and identified the origin of recharge. In addition, the mixture of fresh groundwater with hydrothermal and polluted waters have been estimated. Two main aquifers compose the multilayer system. The upper aquifer is unconfined and consists of sediments and pyroclastic materials. Recharge of this aquifer comes from rainwater and ascending vertical fluids from the lower aquifer. The lower aquifer consists of fractured basalts of Pliocene age. Formerly, the main water source has been the upper unit, which is a porous and unconsolidated unit, which acts as a semi-isotropic aquifer. Intense groundwater usage has resulted in lowering the water table in the upper aquifer. Therefore, the current groundwater extraction is carried out from the deeper aquifer and underlying bedrock units, where fracture flow predominates. Pollution indicators have been reported in

  12. Synthesis of dopamine in E. coli using plasmid-based expression system and its marked effect on host growth profiles.

    Science.gov (United States)

    Das, Arunangshu; Verma, Anita; Mukherjee, Krishna J

    2017-09-14

    L-Dopa and dopamine are important pathway intermediates toward the synthesis of catecholamine such as epinephrine and norepinephrine from amino acid L-tyrosine. Dopamine, secreted from dopaminergic nerve cells, serves as an important neurotransmitter. We report the synthesis of dopamine by extending the aromatic amino acid pathway of Escherichia coli DH5α by the expression of 4-hydroxyphenylacetate-3-hydrolase (HpaBC) from E. coli and an engineered dopa decarboxylase (DDC) from pig kidney cell. The activity of HpaBC and DDC require 200 µM iron supplementation and 50 µM vitamin B6, respectively as additives to the growth media. The maximum concentration of L-dopa and dopamine obtained from the broth was around 26 and 27 mg/L after 24 hr of separate shake flask studies. We observed that in the presence of dopamine synthesized in vivo host growth was remarkably enhanced. These observations lead us to an interesting finding about the role of these catecholamines on bacterial growth. It is clear that synthesis of dopamine in vivo actually promotes growth much efficiently as compared to when dopamine is added to the system from outside. From HPLC and GC-MS data it was further observed that L-dopa was stable within the observable time of experiments whereas dopamine actually was subjected to degradation via oxidation and host consumption.

  13. Vulnerability Analysis of Physical Protection System at Hypothetical Facility

    International Nuclear Information System (INIS)

    Jung, Won Moog; Lee, Ho Jin; Yu, Dong Han; Min, Gyung Sik

    2006-01-01

    Since the 9/11 event in the U.S.A, International terror possibilities has been increasing for nuclear facilities including nuclear power plants(NPPs). It is necessary to evaluate the performance of an existing physical protection system(PPS) at nuclear facilities based on such malevolent acts. A PPS is a complex configuration of detection, delay, and response elements. Detection, delay, and response elements are all important to the analysis and evaluation of a PPS and its effectiveness. Methods are available to analyze a PPS and evaluate its effectiveness. Sandia National Laboratory(SNL) in the U.S.A was developed a System Analysis of Vulnerability to Intrusion (SAVI) computer code for evaluating the effectiveness of PPS against outsider threats. This study presents the vulnerability analysis of the PPS at hypothetical facility using SAVI code that the basic input parameters are from PPS of Hanaro Research Reactor at Korea Atomic Energy Research Institution. It is understand that PPS of research reactor and critical assemblies are deficient that that of NPP and nuclear materials of RRCAS are compact to transport For analysis, first, the site-specific Adversary Sequence Diagrams(ASDs) of the PPS is constructed. It helps to understand the functions of the existing PPS composed of physical areas and Protection Elements(PEs). Then, the most vulnerable path of an ASD as a measure of effectiveness is determined. The results in the analysis can used to suggest the possible PPS upgrades to the most vulnerable paths for the system like research reactor

  14. Source Code Vulnerabilities in IoT Software Systems

    Directory of Open Access Journals (Sweden)

    Saleh Mohamed Alnaeli

    2017-08-01

    Full Text Available An empirical study that examines the usage of known vulnerable statements in software systems developed in C/C++ and used for IoT is presented. The study is conducted on 18 open source systems comprised of millions of lines of code and containing thousands of files. Static analysis methods are applied to each system to determine the number of unsafe commands (e.g., strcpy, strcmp, and strlen that are well-known among research communities to cause potential risks and security concerns, thereby decreasing a system’s robustness and quality. These unsafe statements are banned by many companies (e.g., Microsoft. The use of these commands should be avoided from the start when writing code and should be removed from legacy code over time as recommended by new C/C++ language standards. Each system is analyzed and the distribution of the known unsafe commands is presented. Historical trends in the usage of the unsafe commands of 7 of the systems are presented to show how the studied systems evolved over time with respect to the vulnerable code. The results show that the most prevalent unsafe command used for most systems is memcpy, followed by strlen. These results can be used to help train software developers on secure coding practices so that they can write higher quality software systems.

  15. Vulnerability of the Nordic power system. Executive summary

    International Nuclear Information System (INIS)

    Doorman, Gerard; Kjoeelle, Gerd; Uhlen, Kjetil; Huse, Einar Staale; Flataboe, Nils

    2004-05-01

    The objective of the analysis is to identify the vulnerability of the Nordic power system, identify barriers to reduce vulnerability in a Nordic context and to propose possible actions. The study focuses on vulnerability with respect to energy shortage, capacity shortage and power system failures. Vulnerability is defined with respect to the unwanted situations ''High prices'', ''Curtailment'' and ''Blackouts''. The main tool of the study is risk analysis, where risk is a result of the probability of an event and its consequences. With respect to energy shortage, the system is in a medium risk state. For the present system the probability of a situation like the 2002/03 winter or considerably worse is once every ten years. Under the assumption that power production increases with increasing demand, the situation will be similar towards 2010. In the opposite case, the risk of extremely high prices increases. With respect to capacity shortage, the system is in a low risk state. This is partly due to actions already taken by the TSOs. The risk state will slightly deteriorate towards 2010. With respect to blackouts, the system is in a medium risk state. This is due to the fact that large blackouts in Southern Scandinavia cannot be completely ruled out. Such blackouts involve many consumers resulting in major or potentially even critical consequences. However this is not different from the situation before deregulation. There are no indications that the situation will become worse towards 2010, but there is uncertainty with regard to the effect of changed maintenance routines. Reductions in qualified technical personnel also gives reason for concern. The study identifies significant differences between the Nordic countries with respect to the framework for transmission system investment, system balancing, rules and price setting in the case of curtailment, congestion management and the handling of import and export. Recommended actions include reduction of regulatory

  16. Design and implementation based on the classification protection vulnerability scanning system

    International Nuclear Information System (INIS)

    Wang Chao; Lu Zhigang; Liu Baoxu

    2010-01-01

    With the application and spread of the classification protection, Network Security Vulnerability Scanning should consider the efficiency and the function expansion. It proposes a kind of a system vulnerability from classification protection, and elaborates the design and implementation of a vulnerability scanning system based on vulnerability classification plug-in technology and oriented classification protection. According to the experiment, the application of classification protection has good adaptability and salability with the system, and it also approves the efficiency of scanning. (authors)

  17. A Methodology for Assessing the Seismic Vulnerability of Highway Systems

    International Nuclear Information System (INIS)

    Cirianni, Francis; Leonardi, Giovanni; Scopelliti, Francesco

    2008-01-01

    Modern society is totally dependent on a complex and articulated infrastructure network of vital importance for the existence of the urban settlements scattered on the territory. On these infrastructure systems, usually indicated with the term lifelines, are entrusted numerous services and indispensable functions of the normal urban and human activity.The systems of the lifelines represent an essential element in all the urbanised areas which are subject to seismic risk. It is important that, in these zones, they are planned according to opportune criteria based on two fundamental assumptions: a) determination of the best territorial localization, avoiding, within limits, the places of higher dangerousness; b) application of constructive technologies finalized to the reduction of the vulnerability.Therefore it is indispensable that in any modern process of seismic risk assessment the study of the networks is taken in the rightful consideration, to be integrated with the traditional analyses of the buildings.The present paper moves in this direction, dedicating particular attention to one kind of lifeline: the highway system, proposing a methodology of analysis finalized to the assessment of the seismic vulnerability of the system

  18. Methamphetamine Increases Locomotion and Dopamine Transporter Activity in Dopamine D5 Receptor-Deficient Mice

    OpenAIRE

    Hayashizaki, Seiji; Hirai, Shinobu; Ito, Yumi; Honda, Yoshiko; Arime, Yosefu; Sora, Ichiro; Okado, Haruo; Kodama, Tohru; Takada, Masahiko

    2013-01-01

    Dopamine regulates the psychomotor stimulant activities of amphetamine-like substances in the brain. The effects of dopamine are mediated through five known dopamine receptor subtypes in mammals. The functional relevance of D5 dopamine receptors in the central nervous system is not well understood. To determine the functional relevance of D5 dopamine receptors, we created D5 dopamine receptor-deficient mice and then used these mice to assess the roles of D5 dopamine receptors in the behaviora...

  19. Dopamine system dysregulation by the ventral subiculum as the common pathophysiological basis for schizophrenia psychosis, psychostimulant abuse, and stress.

    Science.gov (United States)

    Grace, Anthony A

    2010-11-01

    The dopamine system is under multiple forms of regulation, and in turn provides effective modulation of system responses. Dopamine neurons are known to exist in several states of activity. The population activity, or the proportion of dopamine neurons firing spontaneously, is controlled by the ventral subiculum of the hippocampus. In contrast, burst firing, which is proposed to be the behaviorally salient output of the dopamine system, is driven by the brainstem pedunculopontine tegmentum (PPTg). When an animal is exposed to a behaviorally salient stimulus, the PPTg elicits a burst of action potentials in the dopamine neurons. However, this bursting only occurs in the portion of the dopamine neuron population that is firing spontaneously. This proportion is regulated by the ventral subiculum. Therefore, the ventral subiculum provides the gain, or the amplification factor, for the behaviorally salient stimulus. The ventral subiculum itself is proposed to carry information related to the environmental context. Thus, the ventral subiculum will adjust the responsivity of the dopamine system based on the needs of the organism and the characteristics of the environment. However, this finely tuned system can be disrupted in disease states. In schizophrenia, a disruption of interneuronal regulation of the ventral subiculum is proposed to lead to an overdrive of the dopamine system, rendering the system in a constant hypervigilant state. Moreover, amphetamine sensitization and stressors also appear to cause an abnormal dopaminergic drive. Such an interaction could underlie the risk factors of drug abuse and stress in the precipitation of a psychotic event. On the other hand, this could point to the ventral subiculum as an effective site of therapeutic intervention in the treatment or even the prevention of schizophrenia.

  20. Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces Amphetamine-Induced Dopamine Release and Reinforcing Effects.

    Science.gov (United States)

    Carpenter, Colleen; Zestos, Alexander G; Altshuler, Rachel; Sorenson, Roderick J; Guptaroy, Bipasha; Showalter, Hollis D; Kennedy, Robert T; Jutkiewicz, Emily; Gnegy, Margaret E

    2017-09-01

    Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH addiction to date, there is urgent need for the identification of druggable targets that mediate the reinforcing action of this stimulant class. AMPH-stimulated dopamine efflux is modulated by protein kinase C (PKC) activation. Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity. The only known CNS-permeant PKC inhibitor is the selective estrogen receptor modulator tamoxifen. In this study, we demonstrate that a tamoxifen analog, 6c, which more potently inhibits PKC than tamoxifen but lacks affinity for the estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine and reinforcement-related behavior. In rat striatal synaptosomes, 6c was almost fivefold more potent at inhibiting AMPH-stimulated dopamine efflux than [ 3 H]dopamine uptake through the dopamine transporter (DAT). The compound did not compete with [ 3 H]WIN 35,428 binding or affect surface DAT levels. Using microdialysis, direct accumbal administration of 1 μM 6c reduced dopamine overflow in freely moving rats. Using LC-MS, we demonstrate that 6c is CNS-permeant. Systemic treatment of rats with 6 mg/kg 6c either simultaneously or 18 h prior to systemic AMPH administration reduced both AMPH-stimulated dopamine overflow and AMPH-induced locomotor effects. Finally, 18 h pretreatment of rats with 6 mg/kg 6c s.c. reduces AMPH-self administration but not food self-administration. These results demonstrate the utility of tamoxifen analogs in reducing AMPH effects on dopamine and reinforcement-related behaviors and suggest a new avenue of development for therapeutics to reduce AMPH abuse.

  1. Vulnerability of water supply systems to cyber-physical attacks

    Science.gov (United States)

    Galelli, Stefano; Taormina, Riccardo; Tippenhauer, Nils; Salomons, Elad; Ostfeld, Avi

    2016-04-01

    The adoption of smart meters, distributed sensor networks and industrial control systems has largely improved the level of service provided by modern water supply systems. Yet, the progressive computerization exposes these critical infrastructures to cyber-physical attacks, which are generally aimed at stealing critical information (cyber-espionage) or causing service disruption (denial-of-service). Recent statistics show that water and power utilities are undergoing frequent attacks - such as the December power outage in Ukraine - , attracting the interest of operators and security agencies. Taking the security of Water Distribution Networks (WDNs) as domain of study, our work seeks to characterize the vulnerability of WDNs to cyber-physical attacks, so as to conceive adequate defense mechanisms. We extend the functionality of EPANET, which models hydraulic and water quality processes in pressurized pipe networks, to include a cyber layer vulnerable to repeated attacks. Simulation results on a medium-scale network show that several hydraulic actuators (valves and pumps, for example) can be easily attacked, causing both service disruption - i.e., water spillage and loss of pressure - and structural damages - e.g., pipes burst. Our work highlights the need for adequate countermeasures, such as attacks detection and reactive control systems.

  2. Report: Results of Technical Vulnerability Assessment: EPA’s Directory Service System Authentication and Authorization Servers

    Science.gov (United States)

    Report #11-P-0597, September 9, 2011. Vulnerability testing of EPA’s directory service system authentication and authorization servers conducted in March 2011 identified authentication and authorization servers with numerous vulnerabilities.

  3. Overexpression of parkin in rat nigrostriatal dopamine system protects against methamphetamine neurotoxicity

    Science.gov (United States)

    Liu, Bin; Traini, Roberta; Killinger, Bryan; Schneider, Bernard; Moszczynska, Anna

    2013-01-01

    Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum, sparing other striatal terminals and cell bodies. We previously detected a deficit in parkin after binge METH in rat striatal synaptosomes. Parkin is an ubiquitin-protein E3 ligase capable of protecting dopamine neurons from diverse cellular insults. Whether the deficit in parkin mediates the toxicity of METH and whether parkin can protect from toxicity of the drug is unknown. The present study investigated whether overexpression of parkin attenuates degeneration of striatal dopaminergic terminals exposed to binge METH. Parkin overexpression in rat nigrostriatal dopamine system was achieved by microinjection of adeno-associated viral transfer vector 2/6 encoding rat parkin (AAV2/6-parkin) into the substantia nigra pars compacta. The microinjections of AAV2/6-parkin dose-dependently increased parkin levels in both the substantia nigra pars compacta and striatum. The levels of dopamine synthesizing enzyme, tyrosine hydroxylase, remained at the control levels; therefore, tyrosine hydroxylase immunoreactivity was used as an index of dopaminergic terminal integrity. In METH-exposed rats, the increase in parkin levels attenuated METH-induced decreases in striatal tyrosine hydroxylase immunoreactivity in a dose-dependent manner, indicating that parkin can protect striatal dopaminergic terminals against METH neurotoxicity. PMID:23313192

  4. Drug abuse: vulnerability and transition to addiction.

    Science.gov (United States)

    Le Moal, M

    2009-05-01

    Intrinsic vulnerability is central to the transition of recreational drug use to misuse. Several factors contribute to vulnerability, inherent or acquired, and they account for the huge individual differences observed concerning the propensity to enter in the addiction process. Some of the multifactional causes for a vulnerable phenotype will be examined: genetic factors, age and gender influences, various comorbidities and epidemiological observations. Stress-induced vulnerability will be particularly reviewed because it provides a good model for a pathophysiological research and for relating environmental events to biological consequences of drug vulnerability, namely through the striato-cortical dopamine system. Experimental studies are generally blind concerning these historical factors that contribute vulnerability and a critical evaluation of current animal models is needed. The transition of the last stage of the process, addiction, is conceptualized as a progression from homeostasis to allostasis and then, to pathology.

  5. Dealing with the vulnerability of the Italian banking system

    Directory of Open Access Journals (Sweden)

    Elisabetta Montanaro

    2017-12-01

    Full Text Available The major vulnerabilities of the Italian banking system are the overhang of NPLs and low profitability. Differently from the attention given to excesses of NPLs, the profitability problem is normally considered to be a matter to be left to bank management and not an area of explicit direct regulatory action. Although focusing on capital requirements, regulators and supervisors seldom pose the question of where capital comes from. Using a large sample of 410 Italian domestic banking groups and individual banks, we propose an NPL stress test and a viability test that show: that the system’s vulnerability is a widespread phenomenon; that a further recapitalisation of around ten billion euro is necessary; and that, more importantly, limiting interventions to the overhang problem does not put the majority of Italian banks into a viability path due to the inefficiencies coming from their current business models. The analysis of the Italian case strengthens the critique of current regulation and supervision because, not focusing on bank profitability, they do not avoid threats on solvency coming from the accumulation of NPLs. We thus argue that the structural changes necessary to put the Italian banking system into a viable path require new regulatory and supervisory approaches.

  6. Vulnerability analysis of complementary transportation systems with applications to railway and airline systems in China

    International Nuclear Information System (INIS)

    Ouyang, Min; Pan, ZheZhe; Hong, Liu; He, Yue

    2015-01-01

    Most of existing studies on vulnerability analysis of multiple infrastructure systems mainly focus on negative effects of interdependencies, which mean that failures in one system can propagate to other systems and aggravate the initial damage. In reality, there also exist positive effects of interdependencies, which are shown in complementary systems and mean that if one system fails another system can provide alternative services to satisfy customers' demands. Different types of transportation systems in a city or country are typical complementary systems. Taking railway and airline systems in China as an example, this paper proposes a network-based approach to model the vulnerability of complementary transportation systems, and based on this model, this paper further introduces a dynamic complementary strength metric, which can help decision makers design or select better complementary topologies from the vulnerability perspective. Also, based on a simple genetic algorithm, this paper analyzes whether critical components for single systems are still important when taking two systems as a whole for analysis. Results show that a protection strategy of hardening a few critical components is also good strategy for the combined system. In addition, the findings and several assumptions are further discussed to close the gap between theory and practice. - Highlights: • We propose a method to model and analyze complementary system vulnerability. • We study vulnerability of complementary railway and airline systems in China. • We propose an approach to quantify dynamic complementary strength. • A few critical components for single systems are important for combined system

  7. Glutamate Receptors within the Mesolimbic Dopamine System Mediate Alcohol Relapse Behavior.

    Science.gov (United States)

    Eisenhardt, Manuela; Leixner, Sarah; Luján, Rafael; Spanagel, Rainer; Bilbao, Ainhoa

    2015-11-25

    Glutamatergic input within the mesolimbic dopamine (DA) pathway plays a critical role in the development of addictive behavior. Although this is well established for some drugs of abuse, it is not known whether glutamate receptors within the mesolimbic system are involved in mediating the addictive properties of chronic alcohol use. Here we evaluated the contribution of mesolimbic NMDARs and AMPARs in mediating alcohol-seeking responses induced by environmental stimuli and relapse behavior using four inducible mutant mouse lines lacking the glutamate receptor genes Grin1 or Gria1 in either DA transporter (DAT) or D1R-expressing neurons. We first demonstrate the lack of GluN1 or GluA1 in either DAT- or D1R-expressing neurons in our mutant mouse lines by colocalization studies. We then show that GluN1 and GluA1 receptor subunits within these neuronal subpopulations mediate the alcohol deprivation effect, while having no impact on context- plus cue-induced reinstatement of alcohol-seeking behavior. We further validated these results pharmacologically by demonstrating similar reductions in the alcohol deprivation effect after infusion of the NMDAR antagonist memantine into the nucleus accumbens and ventral tegmental area of control mice, and a rescue of the mutant phenotype via pharmacological potentiation of AMPAR activity using aniracetam. In conclusion, dopamine neurons as well as D1R-expressing medium spiny neurons and their glutamatergic inputs via NMDARs and AMPARs act in concert to influence relapse responses. These results provide a neuroanatomical and molecular substrate for relapse behavior and emphasize the importance of glutamatergic drugs in modulating relapse behavior. Here we provide genetic and pharmacological evidence that glutamate receptors within the mesolimbic dopamine system play an essential role in alcohol relapse. Using various inducible and site-specific transgenic mouse models and pharmacological validation experiments, we show that critical

  8. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

  9. Single Point Vulnerability Analysis of Automatic Seismic Trip System

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Seo Bin; Chung, Soon Il; Lee, Yong Suk [FNC Technology Co., Yongin (Korea, Republic of); Choi, Byung Pil [KHNP CRI, Daejeon (Korea, Republic of)

    2016-10-15

    Single Point Vulnerability (SPV) analysis is a process used to identify individual equipment whose failure alone will result in a reactor trip, turbine generator failure, or power reduction of more than 50%. Automatic Seismic Trip System (ASTS) is a newly installed system to ensure the safety of plant when earthquake occurs. Since this system directly shuts down the reactor, the failure or malfunction of its system component can cause a reactor trip more frequently than other systems. Therefore, an SPV analysis of ASTS is necessary to maintain its essential performance. To analyze SPV for ASTS, failure mode and effect analysis (FMEA) and fault tree analysis (FTA) was performed. In this study, FMEA and FTA methods were performed to select SPV equipment of ASTS. D/O, D/I, A/I card, seismic sensor, and trip relay had an effect on the reactor trip but their single failure will not cause reactor trip. In conclusion, ASTS is excluded as SPV. These results can be utilized as the basis data for ways to enhance facility reliability such as design modification and improvement of preventive maintenance procedure.

  10. Single Point Vulnerability Analysis of Automatic Seismic Trip System

    International Nuclear Information System (INIS)

    Oh, Seo Bin; Chung, Soon Il; Lee, Yong Suk; Choi, Byung Pil

    2016-01-01

    Single Point Vulnerability (SPV) analysis is a process used to identify individual equipment whose failure alone will result in a reactor trip, turbine generator failure, or power reduction of more than 50%. Automatic Seismic Trip System (ASTS) is a newly installed system to ensure the safety of plant when earthquake occurs. Since this system directly shuts down the reactor, the failure or malfunction of its system component can cause a reactor trip more frequently than other systems. Therefore, an SPV analysis of ASTS is necessary to maintain its essential performance. To analyze SPV for ASTS, failure mode and effect analysis (FMEA) and fault tree analysis (FTA) was performed. In this study, FMEA and FTA methods were performed to select SPV equipment of ASTS. D/O, D/I, A/I card, seismic sensor, and trip relay had an effect on the reactor trip but their single failure will not cause reactor trip. In conclusion, ASTS is excluded as SPV. These results can be utilized as the basis data for ways to enhance facility reliability such as design modification and improvement of preventive maintenance procedure

  11. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

    Science.gov (United States)

    Pfeifer, Philippe; Tüscher, Oliver; Buchholz, Hans Georg; Gründer, Gerhard; Vernaleken, Ingo; Paulzen, Michael; Zimmermann, Ulrich S; Maus, Stephan; Lieb, Klaus; Eggermann, Thomas; Fehr, Christoph; Schreckenberger, Mathias

    2017-09-01

    Investigations on the acute effects of alcohol in the human mesolimbic dopamine D 2 /D 3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D 2 /D 3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D 2 /D 3 receptor ligand [ 18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D 2 /D 3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP ND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP ND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D 2 /D 3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D 2 /D 3 receptors may hint at an addiction relevant trait. © 2016 Society for the Study of Addiction.

  12. Assessment of human-natural system characteristics influencing global freshwater supply vulnerability

    Science.gov (United States)

    Padowski, Julie C.; Gorelick, Steven M.; Thompson, Barton H.; Rozelle, Scott; Fendorf, Scott

    2015-10-01

    Global freshwater vulnerability is a product of environmental and human dimensions, however, it is rarely assessed as such. Our approach identifies freshwater vulnerability using four broad categories: endowment, demand, infrastructure, and institutions, to capture impacts on natural and managed water systems within the coupled human-hydrologic environment. These categories are represented by 19 different endogenous and exogenous characteristics affecting water supply vulnerability. By evaluating 119 lower per capita income countries (Yemen and Djibouti nearly as vulnerable. Surprising similarities in vulnerability were also found among geographically disparate nations such as Vietnam, Sri Lanka, and Guatemala. Determining shared patterns of freshwater vulnerability provides insights into why water supply vulnerabilities are manifested in human-water systems at the national scale.

  13. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong; Hu Mingyang; Pan Shangren; Wang Bocheng

    1996-01-01

    To study preparation of central nerves system dopamine D2 imaging agent 131 I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated 125 I-IBZM and 131 I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of 125 I-IBZM and 131 I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: K d = 0.53 +- 0.06 nmol/L, B max = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high 125 I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high 125 -IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. 131 I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat's and rabbit's central nerves system dopamine D2 receptors

  14. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    Energy Technology Data Exchange (ETDEWEB)

    Yansong, Lin; Xiangtong, Lin; Mingyang, Hu; Shangren, Pan; Bocheng, Wang [Huashan Hospital of Shanghai Medical Univ., Shanghai (China)

    1996-11-01

    To study preparation of central nerves system dopamine D2 imaging agent {sup 131}I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated {sup 125}I-IBZM and {sup 131}I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of {sup 125}I-IBZM and {sup 131}I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: K{sub d} = 0.53 +- 0.06 nmol/L, B{sub max} = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high {sup 125}I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high {sup 125}-IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. {sup 131}I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat`s and rabbit`s central nerves system dopamine D2 receptors.

  15. Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

    Science.gov (United States)

    Torres-Rosas, Rafael; Yehia, Ghassan; Peña, Geber; Mishra, Priya; del Rocio Thompson-Bonilla, Maria; Moreno-Eutimio, Mario Adán; Arriaga-Pizano, Lourdes Andrea; Isibasi, Armando; Ulloa, Luis

    2014-01-01

    Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders. PMID:24562381

  16. National legal system in relation to vulnerable population groups

    Directory of Open Access Journals (Sweden)

    Sjeničić Marta

    2015-01-01

    Full Text Available Vulnerable social groups can be recognized in everyday life, and local legal regulations identify them as well. Strategies and laws clearly identify the increased needs of vulnerable groups. Local legislation, for example, observes comparative law trends and attempts to prevent discrimination of persons with disabilities, emphasizes their human rights and creates the legal framework for taking these persons out of the institutional form of protection and including them into the community. In Serbia however, strategies and laws, as well as by-laws, are written in sectors, and not in cross-sectors manner. Proper caring for persons with disabilities, including persons with mental disabilities, requires an integral approach, namely a mutual approach of the social, health, educational and other sectors. True enough, local regulations stress the need for an intersectional approach, but such an approach is scantily applied in practice, so the comprehensive care that would satisfy the multiple needs of persons with mental disabilities often turns out to be less than expected in the community. Pursuant to national laws and basic ethic principals, all citizens of the Republic of Serbia have the right to health protection without discrimination. Therefore, methods for using health protection, easier than the existing ones, should be found for certain vulnerable groups, depending on their characteristics, and so for the Roma as well, and bearing in mind that systemic health regulations in Serbia open the door to special treatment of these groups. The inaccessible approach to health care of the Roma population persists primarily due to insufficient basic health documentation and basic personal documentation. Personal documents are linked with the registered place of residence, which the Roma, largely do not have. The problem is thus on a wider scale and is not only focused on the health sector. As such, it requires a wider, intersectional approach and a

  17. Epigenetic dysregulation of the dopamine system in diet-induced obesity.

    Science.gov (United States)

    Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

    2012-03-01

    Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  18. Specificity and impact of adrenergic projections to the midbrain dopamine system

    Science.gov (United States)

    Mejias-Aponte, Carlos A.

    2016-01-01

    Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson’s disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. PMID:26820641

  19. Development of information security and vulnerability risk management system for J-PARC

    International Nuclear Information System (INIS)

    Ishikawa, Hiroyuki; Tate, Akihiro; Murakami, Tadashi

    2012-02-01

    In J-PARC (Japan Proton Accelerator Research Complex) we have set up intra-network (internal network, we will abbreviate it as JLAN, below) to support research activity and communication among users. In JLAN, we set up various kinds of security devices to keep JLAN secure. However, the servers which provide information or service to public are still in danger of being accessed illegally. If there is an illegal access, that may cause defacement of data or information leak. Furthermore, the victim servers are manipulated by the malicious attackers, and they themselves attack the external information equipments. Vulnerability of servers enables unauthorized access. So, vulnerability test with use of a vulnerability tool is one of the most effective ways to take measures for vulnerability of the equipments. However, it is not enough to just conduct a vulnerability test. It is also essential for information security to take measures to cover constantly for the vulnerability of servers. We focused on the points above, and developed the vulnerability testing system for security. It is not only a testing tool for the vulnerability of servers, but also management system which enables the server administrators in charge of taking measures for vulnerabilities to manage risks and handles PDCA (Plan-Do-Check-Action) cycles as countermeasure for vulnerability. In this paper, we report the technologies and ingenuities for the development of the above system. (author)

  20. Systemic effects of low-dose dopamine during administration of cytarabine.

    Science.gov (United States)

    Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

    2017-09-01

    Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

  1. Guiding climate change adaptation within vulnerable natural resource management systems.

    Science.gov (United States)

    Bardsley, Douglas K; Sweeney, Susan M

    2010-05-01

    Climate change has the potential to compromise the sustainability of natural resources in Mediterranean climatic systems, such that short-term reactive responses will increasingly be insufficient to ensure effective management. There is a simultaneous need for both the clear articulation of the vulnerabilities of specific management systems to climate risk, and the development of appropriate short- and long-term strategic planning responses that anticipate environmental change or allow for sustainable adaptive management in response to trends in resource condition. Governments are developing climate change adaptation policy frameworks, but without the recognition of the importance of responding strategically, regional stakeholders will struggle to manage future climate risk. In a partnership between the South Australian Government, the Adelaide and Mt Lofty Ranges Natural Resource Management Board and the regional community, a range of available research approaches to support regional climate change adaptation decision-making, were applied and critically examined, including: scenario modelling; applied and participatory Geographical Information Systems modelling; environmental risk analysis; and participatory action learning. As managers apply ideas for adaptation within their own biophysical and socio-cultural contexts, there would be both successes and failures, but a learning orientation to societal change will enable improvements over time. A base-line target for regional responses to climate change is the ownership of the issue by stakeholders, which leads to an acceptance that effective actions to adapt are now both possible and vitally important. Beyond such baseline knowledge, the research suggests that there is a range of tools from the social and physical sciences available to guide adaptation decision-making.

  2. Guiding Climate Change Adaptation Within Vulnerable Natural Resource Management Systems

    Science.gov (United States)

    Bardsley, Douglas K.; Sweeney, Susan M.

    2010-05-01

    Climate change has the potential to compromise the sustainability of natural resources in Mediterranean climatic systems, such that short-term reactive responses will increasingly be insufficient to ensure effective management. There is a simultaneous need for both the clear articulation of the vulnerabilities of specific management systems to climate risk, and the development of appropriate short- and long-term strategic planning responses that anticipate environmental change or allow for sustainable adaptive management in response to trends in resource condition. Governments are developing climate change adaptation policy frameworks, but without the recognition of the importance of responding strategically, regional stakeholders will struggle to manage future climate risk. In a partnership between the South Australian Government, the Adelaide and Mt Lofty Ranges Natural Resource Management Board and the regional community, a range of available research approaches to support regional climate change adaptation decision-making, were applied and critically examined, including: scenario modelling; applied and participatory Geographical Information Systems modelling; environmental risk analysis; and participatory action learning. As managers apply ideas for adaptation within their own biophysical and socio-cultural contexts, there would be both successes and failures, but a learning orientation to societal change will enable improvements over time. A base-line target for regional responses to climate change is the ownership of the issue by stakeholders, which leads to an acceptance that effective actions to adapt are now both possible and vitally important. Beyond such baseline knowledge, the research suggests that there is a range of tools from the social and physical sciences available to guide adaptation decision-making.

  3. Reversal of dopamine system dysfunction in response to high-fat diet.

    Science.gov (United States)

    Carlin, Jesselea; Hill-Smith, Tiffany E; Lucki, Irwin; Reyes, Teresa M

    2013-12-01

    To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD. Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR. After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region. These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention. Copyright © 2013 The Obesity Society.

  4. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitoxicity and Environmental, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2002-01-01

    .... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U.S...

  5. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2005-01-01

    .... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U.S...

  6. Gender-specific roles for the melanocortin-3 receptor in the regulation of the mesolimbic dopamine system in mice.

    Science.gov (United States)

    Lippert, Rachel N; Ellacott, Kate L J; Cone, Roger D

    2014-05-01

    The melanocortin-3 receptor (MC3R) and MC4R are known to play critical roles in energy homeostasis. However, the physiological functions of the MC3R remain poorly understood. Earlier reports indicated that the ventral tegmental area (VTA) is one of the highest sites of MC3R expression, and we sought to determine the function of the receptor in this brain region. A MC3R-green-fluorescent protein transgenic mouse and a MC3R knockout mouse strain were used to characterize the neurochemical identity of the MC3R neurons in the VTA and to determine the effects of global MC3R deletion on VTA dopamine (DA) homeostasis. We demonstrate that the MC3R, but not MC4R, is expressed in up to a third of dopaminergic neurons of the VTA. Global deletion of the MC3R increases total dopamine by 42% in the VTA and decreases sucrose intake and preference in female but not male mice. Ovariectomy restores dopamine levels to normal, but aberrant decreased VTA dopamine levels are also observed in prepubertal female mice. Because arcuate Agouti-related peptide/neuropeptide Y neurons are known to innervate and regulate VTA signaling, the MC3R in dopaminergic neurons provides a specific input for communication of nutritional state within the mesolimbic dopamine system. Data provided here suggest that this input may be highly sexually dimorphic, functioning as a specific circuit regulating effects of estrogen on VTA dopamine levels and on sucrose preference. Overall, this data support a sexually dimorphic function of MC3R in regulation of the mesolimbic dopaminergic system and reward.

  7. Vulnerability analysis and critical areas identification of the power systems under terrorist attacks

    Science.gov (United States)

    Wang, Shuliang; Zhang, Jianhua; Zhao, Mingwei; Min, Xu

    2017-05-01

    This paper takes central China power grid (CCPG) as an example, and analyzes the vulnerability of the power systems under terrorist attacks. To simulate the intelligence of terrorist attacks, a method of critical attack area identification according to community structures is introduced. Meanwhile, three types of vulnerability models and the corresponding vulnerability metrics are given for comparative analysis. On this basis, influence of terrorist attacks on different critical areas is studied. Identifying the vulnerability of different critical areas will be conducted. At the same time, vulnerabilities of critical areas under different tolerance parameters and different vulnerability models are acquired and compared. Results show that only a few number of vertex disruptions may cause some critical areas collapse completely, they can generate great performance losses the whole systems. Further more, the variation of vulnerability values under different scenarios is very large. Critical areas which can cause greater damage under terrorist attacks should be given priority of protection to reduce vulnerability. The proposed method can be applied to analyze the vulnerability of other infrastructure systems, they can help decision makers search mitigation action and optimum protection strategy.

  8. Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

    Science.gov (United States)

    Yang, Chen; Ge, Shun-Nan; Zhang, Jia-Rui; Chen, Lei; Yan, Zhi-Qiang; Heng, Li-Jun; Zhao, Tian-Zhi; Li, Wei-Xin; Jia, Dong; Zhu, Jun-Ling; Gao, Guo-Dong

    2013-01-01

    High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

  9. Integrating Social impacts on Health and Health-Care Systems in Systemic Seismic Vulnerability Analysis

    Science.gov (United States)

    Kunz-Plapp, T.; Khazai, B.; Daniell, J. E.

    2012-04-01

    This paper presents a new method for modeling health impacts caused by earthquake damage which allows for integrating key social impacts on individual health and health-care systems and for implementing these impacts in quantitative systemic seismic vulnerability analysis. In current earthquake casualty estimation models, demand on health-care systems is estimated by quantifying the number of fatalities and severity of injuries based on empirical data correlating building damage with casualties. The expected number of injured people (sorted by priorities of emergency treatment) is combined together with post-earthquake reduction of functionality of health-care facilities such as hospitals to estimate the impact on healthcare systems. The aim here is to extend these models by developing a combined engineering and social science approach. Although social vulnerability is recognized as a key component for the consequences of disasters, social vulnerability as such, is seldom linked to common formal and quantitative seismic loss estimates of injured people which provide direct impact on emergency health care services. Yet, there is a consensus that factors which affect vulnerability and post-earthquake health of at-risk populations include demographic characteristics such as age, education, occupation and employment and that these factors can aggravate health impacts further. Similarly, there are different social influences on the performance of health care systems after an earthquake both on an individual as well as on an institutional level. To link social impacts of health and health-care services to a systemic seismic vulnerability analysis, a conceptual model of social impacts of earthquakes on health and the health care systems has been developed. We identified and tested appropriate social indicators for individual health impacts and for health care impacts based on literature research, using available European statistical data. The results will be used to

  10. Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study

    NARCIS (Netherlands)

    da Silva Alves, Fabiana; Schmitz, Nicole; Figee, Martijn; Abeling, Nico; Hasler, Gregor; van der Meer, Johan; Nederveen, Aart; de Haan, Lieuwe; Linszen, Don; van Amelsvoort, Therese

    2011-01-01

    Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity

  11. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  12. Extreme climatic events: reducing ecological and social systems vulnerabilities

    International Nuclear Information System (INIS)

    Decamps, H.; Amatore, C.; Bach, J.F.; Baccelli, F.; Balian, R.; Carpentier, A.; Charnay, P.; Cuzin, F.; Davier, M.; Dercourt, J.; Dumas, C.; Encrenaz, P.; Jeannerod, M.; Kahane, J.P.; Meunier, B.; Rebut, P.H.; Salencon, J.; Spitz, E.; Suquet, P.; Taquet, P.; Valleron, A.J.; Yoccoz, J.C.; Chapron, J.Y.; Fanon, J.; Andre, J.C.; Auger, P.; Bourrelier, P.H.; Combes, C.; Derrida, B.; Laubier, L.; Laval, K.; Le Maho, Y.; Marsily, G. De; Petit, M.; Schmidt-Laine, C.; Birot, Y.; Peyron, J.L.; Seguin, B.; Barles, S.; Besancenot, J.P.; Michel-Kerjan, E.; Hallegatte, S.; Dumas, P.; Ancey, V.; Requier-Desjardins, M.; Ducharnes, A.; Ciais, P.; Peylin, P.; Kaniewski, D.; Van Campo, E.; Planton, S.; Manuguerra, J.C.; Le Bars, Y.; Lagadec, P.; Kessler, D.; Pontikis, C.; Nussbaum, R.

    2010-01-01

    The Earth has to face more and more devastating extreme events. Between 1970 and 2009, at the worldwide scale, the 25 most costly catastrophes all took place after 1987, and for more than half of them after 2001. Among these 25 catastrophes, 23 were linked to climate conditions. France was not spared: the December 1999 storms led to 88 deaths, deprived 3.5 million households of electricity and costed more than 9 billion euros. The 2003 heat wave led to about 15000 supernumerary deaths between August 1 and August 20. The recent Xynthia storm, with its flood barrier ruptures, provoked 53 deaths in addition to many other tragedies that took place in areas liable to flooding. In the present day context of climate change, we know that we must be prepared to even more dangerous events, sometimes unexpected before. These events can have amplified effects because of the urban development, the overpopulation of coastal areas and the anthropization of natural environments. They represent real 'poverty traps' for the poorest countries of the Earth. The anticipation need is real but is our country ready to answer it? Does it have a sufficient contribution to international actions aiming at reducing risks? Is his scientific information suitable? France is not less vulnerable than other countries. It must reinforce its prevention, its response and resilience capacities in the framework of integrated policies of catastrophes risk management as well as in the framework of climate change adaptation plans. This reinforcement supposes the development of vigilance systems with a better risk coverage and benefiting by the advances gained in the meteorology and health domains. It supposes a town and country planning allowing to improve the viability of ecological and social systems - in particular by protecting their diversity. Finally, this reinforcement requires inciting financial coverage solutions for catastrophes prevention and for their management once they have taken place. A

  13. Critical Vulnerability: Defending the Decisive Point of United States Computer Networked Information Systems

    National Research Council Canada - National Science Library

    Virden, Roy

    2003-01-01

    .... The military's use of computer networked information systems is thus a critical strength. These systems are then critical vulnerabilities because they may lack adequate protection and are open to enemy attack...

  14. Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

    International Nuclear Information System (INIS)

    Fedi, M.; Berkovic, S.F.; Tochon-Danguy, H.J.; Reutens, D.C.

    2002-01-01

    Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p 0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  15. You are what you eat: influence of type and amount of food consumed on central dopamine systems and the behavioral effects of direct- and indirect-acting dopamine receptor agonists.

    Science.gov (United States)

    Baladi, Michelle G; Daws, Lynette C; France, Charles P

    2012-07-01

    The important role of dopamine (DA) in mediating feeding behavior and the positive reinforcing effects of some drugs is well recognized. Less widely studied is how feeding conditions might impact the sensitivity of drugs acting on DA systems. Food restriction, for example, has often been the focus of aging and longevity studies; however, other studies have demonstrated that mild food restriction markedly increases sensitivity to direct- and indirect-acting DA receptor agonists. Moreover, it is becoming clear that not only the amount of food, but the type of food, is an important factor in modifying the effects of drugs. Given the increased consumption of high fat and sugary foods, studies are exploring how consumption of highly palatable food impacts DA neurochemistry and the effects of drugs acting on these systems. For example, eating high fat chow increases sensitivity to some behavioral effects of direct- as well as indirect-acting DA receptor agonists. A compelling mechanistic possibility is that central DA pathways that mediate the effects of some drugs are regulated by one or more of the endocrine hormones (e.g. insulin) that undergo marked changes during food restriction or after consuming high fat or sugary foods. Although traditionally recognized as an important signaling molecule in regulating energy homeostasis, insulin can also regulate DA neurochemistry. Because direct- and indirect-acting DA receptor drugs are used therapeutically and some are abused, a better understanding of how food intake impacts response to these drugs would likely facilitate improved treatment of clinical disorders and provide information that would be relevant to the causes of vulnerability to abuse drugs. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Vulnerability effects of passengers' intermodal transfer distance preference and subway expansion on complementary urban public transportation systems

    International Nuclear Information System (INIS)

    Hong, Liu; Yan, Yongze; Ouyang, Min; Tian, Hui; He, Xiaozheng

    2017-01-01

    The vulnerability studies on urban public transportation systems have attracted growing attentions in recent years, due to their important role in the economy development of a city and the well-beings of its citizens. This paper proposes a vulnerability model of complementary urban public transportation systems (CUPTSs) composed of bus systems and subway systems, with the consideration of passengers’ intermodal transfer distance preference (PITDP) to capture different levels of complementary strength between the two systems. Based on the model, this paper further introduces a CUPTSs-aimed vulnerability analysis method from two specific aspects: (a) vulnerability effects of different PITDP values, which facilitate the design of policies to change PITDP to reduce system vulnerability; (b) vulnerability effects of different subway expansion plans, which facilitate the vulnerability investigation of current expansion plan and the identification of the optimal expansion plan from the system vulnerability perspective. The proposed CUPTSs-aimed vulnerability analysis method is applied to investigate the complementary bus and subway systems in the city of Wuhan, China. The insights from this study are helpful to analyze other CUPTSs for valuable planning suggestions from the vulnerability perspective. - Highlights: • We model complementary urban public transportation systems’ (CUPTSs) vulnerability. • We use a PITDP metric to capture different levels of complementary relationship. • We study vulnerability under different PITDP and different subway expansion plans. • We analyze dynamic vulnerability of CUPTSs during their expansion process.

  17. Rat brain sagittal organotypic slice cultures as an ex vivo dopamine cell loss system.

    Science.gov (United States)

    McCaughey-Chapman, Amy; Connor, Bronwen

    2017-02-01

    Organotypic brain slice cultures are a useful tool to study neurological function as they provide a more complex, 3-dimensional system than standard 2-dimensional in vitro cell cultures. Building on a previously developed mouse brain slice culture protocol, we have developed a rat sagittal brain slice culture system as an ex vivo model of dopamine cell loss. We show that rat brain organotypic slice cultures remain viable for up to 6 weeks in culture. Using Fluoro-Gold axonal tracing, we demonstrate that the slice 3-dimensional cytoarchitecture is maintained over a 4 week culturing period, with particular focus on the nigrostriatal pathway. Treatment of the cultures with 6-hydroxydopamine and desipramine induces a progressive loss of Fluoro-Gold-positive nigral cells with a sustained loss of tyrosine hydroxylase-positive nigral cells. This recapitulates the pattern of dopaminergic degeneration observed in the rat partial 6-hydroxydopamine lesion model and, most importantly, the progressive pathology of Parkinson's disease. Our slice culture platform provides an advance over other systems, as we demonstrate for the first time 3-dimensional cytoarchitecture maintenance of rat nigrostriatal sagittal slices for up to 6 weeks. Our ex vivo organotypic slice culture system provides a long term cellular platform to model Parkinson's disease, allowing for the elucidation of mechanisms involved in dopaminergic neuron degeneration and the capability to study cellular integration and plasticity ex vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2001-01-01

    .... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is rapidly becoming a widespread problem and drug of abuse throughout the U.S...

  19. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2000-01-01

    .... Similarly, the psycho stimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is rapidly becoming a widespread problem and drug of abuse throughout the U.S...

  20. Swim stress exaggerates the hyperactive mesocortical dopamine system in a rodent model of autism.

    Science.gov (United States)

    Nakasato, Akane; Nakatani, Yasushi; Seki, Yoshinari; Tsujino, Naohisa; Umino, Masahiro; Arita, Hideho

    2008-02-08

    Several clinical reports have suggested that there is a hyperactivation of the dopaminergic system in people with autism. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we measured dopamine (DA) levels in samples collected from the frontal cortex (FC) using in vivo microdialysis and HPLC. The basal DA level in FC was significantly higher in VPA-exposed rats relative to controls. Since the mesocortical DA system is known to be sensitive to physical and psychological stressors, we measured DA levels in FC before, during, and after a 60-min forced swim test (FST). There were further gradual increases in FC DA levels during the FST in the VPA-exposed rats, but not in the control rats. Behavioral analysis during the last 10 min of the FST revealed a significant decrease in active, escape-oriented behavior and an increase in immobility, which is thought to reflect the development of depressive behavior that disengages the animal from active forms of coping with stressful stimuli. These results suggest that this rodent model of autism exhibits a hyperactive mesocortical DA system, which is exaggerated by swim stress. This abnormality may be responsible for depressive and withdrawal behavior observed in autism.

  1. METHODOLOGICAL APPROACH TO ANALYSIS AND EVALUATION OF INFORMATION PROTECTION IN INFORMATION SYSTEMS BASED ON VULNERABILITY DANGER

    Directory of Open Access Journals (Sweden)

    Y. M. Krotiuk

    2008-01-01

    Full Text Available The paper considers a methodological approach to an analysis and estimation of information security in the information systems which is based on the analysis of vulnerabilities and an extent of their hazard. By vulnerability hazard it is meant a complexity of its operation as a part of an information system. The required and sufficient vulnerability operational conditions  have  been  determined in the paper. The paper proposes a generalized model for attack realization which is used as a basis for construction of an attack realization model for an operation of a particular vulnerability. A criterion for estimation of information protection in the information systems which is based on the estimation of vulnerability hazard is formulated in the paper. The proposed approach allows to obtain a quantitative estimation of the information system security on the basis of the proposed schemes on realization of typical attacks for the distinguished classes of vulnerabilities.The methodical approach is used for choosing variants to be applied for realization of protection mechanisms in the information systems as well as for estimation of information safety in the operating information systems.

  2. The mechanisms of neurotoxicity and the selective vulnerability of nervous system sites.

    Science.gov (United States)

    Maurer, Laura L; Philbert, Martin A

    2015-01-01

    The spatial heterogeneity of the structure, function, and cellular composition of the nervous system confers extraordinary complexity and a multiplicity of mechanisms of chemical neurotoxicity. Because of its relatively high metabolic demands and functional dependence on postmitotic neurons, the nervous system is vulnerable to a variety of xenobiotics that affect essential homeostatic mechanisms that support function. Despite protection from the neuroglia and blood-brain barrier, the central nervous system is prone to attack from lipophilic toxicants and those that hijack endogenous transport, receptor, metabolic, and other biochemical systems. The inherent predilection of chemicals for highly conserved biochemical systems confers selective vulnerability of the nervous system to neurotoxicants. This chapter discusses selective vulnerability of the nervous system in the context of neuron-specific decrements (axonopathy, myelinopathy, disruption of neurotransmission), and the degree to which neuronal damage is facilitated or ameliorated by surrounding nonneural cells in both the central and peripheral nervous systems. © 2015 Elsevier B.V. All rights reserved.

  3. The nigrostriatal dopamine system of aging GFRα-1 heterozygous mice: neurochemistry, morphology and behavior

    Science.gov (United States)

    Zaman, Vandana; Boger, Heather A.; Granholm, Ann-Charlotte; Rohrer, Baerbel; Moore, Alfred; Buhusi, Mona; Gerhardt, Greg A.; Hoffer, Barry J.; Middaugh, Lawrence D.

    2009-01-01

    Given the established importance of glial cell line-derived neurotrophic factor (GDNF) in maintaining dopaminergic neurotransmitter systems, the nigrostriatal system and associated behaviors of mice with genetic reduction of its high-affinity receptor, GDNF receptor (GFR)α-1 (GFRα-1+/−), were compared with wild-type controls. Motor activity and the stimulatory effects of a dopamine (DA) D1 receptor agonist (SKF 82958) were assessed longitudinally at 8 and 18 months of age. Monoamine concentrations and dopaminergic nerve terminals in the striatum and the number of dopaminergic neurons in the substantia nigra (SN) were assessed. The results support the importance of GFRα-1 in maintaining normal function of the nigrostriatal dopaminergic system, with deficits being observed for GFRα-1+/− mice at both ages. Motor activity was lower and the stimulatory effects of the DA agonist were enhanced for the older GFRα-1+/− mice. DA in the striatum was reduced in the GFRα-1+/− mice at both ages, and tyrosine hydroxylase-positive cell numbers in the SN were reduced most substantially in the older GFRα-1+/− mice. The combined behavioral, pharmacological probe, neurochemical and morphological measures provide evidence of abnormalities in GFRα-1+/− mice that are indicative of an exacerbated aging-related decline in dopaminergic system function. The noted deficiencies, in turn, suggest that GFRα-1 is necessary for GDNF to maintain normal function of the nigrostriatal dopaminergic system. Although the precise mechanism(s) for the aging-related changes in the dopaminergic system remain to be established, the present study clearly establishes that genetic reductions in GFRα-1 can contribute to the degenerative changes observed in this system during the aging process. PMID:18973577

  4. Anticipating Vulnerability to Climate Change in Dryland Pastoral Systems: Using Dynamic Systems Models for the Kalahari

    Directory of Open Access Journals (Sweden)

    Andrew J. Dougill

    2010-06-01

    Full Text Available It is vitally important to identify agroecosystems that may cease functioning because of changing climate or land degradation. However, identifying such systems is confounded on both conceptual and methodological grounds, especially in systems that are moving toward thresholds, a common trait of dryland environments. This study explores these challenges by analyzing how a range of external pressures affect the vulnerability of dryland pastoral systems in the Kalahari. This is achieved by employing dynamic systems modeling approaches to understand the pathways by which communities became vulnerable to drought. Specifically, we evaluate how external pressures have changed: (1 different agroecosystems' abilities to tolerate drought, i.e., ecosystem resilience; (2 rural communities' abilities to adapt to drought, mediated via their access to assets; and (3 the ability of institutions and policy interventions to play a role in mediating drought-related crises, i.e., socio-political governance. This is done by reanalyzing ecological and participatory research findings along with farm-scale livestock offtake data from across the Kalahari in Botswana. An iterative process was followed to establish narratives exploring how external drivers led to changes in agroecosystem resilience, access to assets, and the institutional capacity to buffer the system. We use "causal loop diagrams" and statistical dynamic system models to express key quantitative relationships and establish future scenarios to help define where uncertainties lie by showing where the system is most sensitive to change. We highlight how that greater sharing of land management knowledge and practices between private and communal land managers can provide 'win-win-win' benefits of reducing system vulnerability, increasing economic income, and building social capital. We use future scenario analyses to identify key areas for future studies of climate change adaptation across the Kalahari.

  5. Wireless Instantaneous Neurotransmitter Concentration System-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring.

    Science.gov (United States)

    Agnesi, Filippo; Tye, Susannah J; Bledsoe, Jonathan M; Griessenauer, Christoph J; Kimble, Christopher J; Sieck, Gary C; Bennet, Kevin E; Garris, Paul A; Blaha, Charles D; Lee, Kendall H

    2009-10-01

    In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig. The

  6. Vulnerability of ecological systems to climatic effects of nuclear war

    International Nuclear Information System (INIS)

    Harwell, M.A.; Hutchinson, T.C.; Cropper, W.P. Jr.; Harwell, C.C.

    1985-01-01

    The authors' analyses are based on a suite of approaches: physiological information, historical analogs, simulation and statistical analyses, and expert judgment. Because of the great complexity of ecosystems across the global landscape and the temporal and spatial complexity of potential nuclear-war induced climatic disturbances, it is not possible uniquely to characterize the effects on ecosystems. A biome approach has been chosen as an appropriate level for generalization of potential effects. Northern Hemisphere temperate terrestrial ecosystems, aquatic ecosystems, tropical ecosystems, and Southern Hemisphere extra-tropical ecosystems are addressed. The ecosystem discussions emphasize effects on the primary producers, in large part because those components are fundamental to the total ecosystem and are often especially vulnerable to the types of perturbations considered here. Estimates of effects on fauna are largely based on those mediated through changes in food supplies. Further study of effects on trophic structures and of indirect effects on species propagated through the complex interactions of ecosystems is required

  7. The vulnerabilities of the power-grid system: renewable microgrids as an alternative source of energy.

    Science.gov (United States)

    Meyer, Victor; Myres, Charles; Bakshi, Nitin

    2010-03-01

    The objective of this paper is to analyse the vulnerabilities of current power-grid systems and to propose alternatives to using fossil fuel power generation and infrastructure solutions in the form of microgrids, particularly those from renewable energy sources. One of the key potential benefits of microgrids, apart from their inherent sustainability and ecological advantages, is increased resilience. The analysis is targeted towards the context of business process outsourcing in India. However, much of the research on vulnerabilities has been derived from the USA and as such many of the examples cite vulnerabilities in the USA and other developed economies. Nevertheless, the vulnerabilities noted are to a degree common to all grid systems, and so the analysis may be more broadly applicable.

  8. Modelling social vulnerability in sub-Saharan West Africa using a geographical information system

    Directory of Open Access Journals (Sweden)

    Olanrewaju Lawal

    2015-05-01

    Full Text Available In recent times, disasters and risk management have gained significant attention, especially with increasing awareness of the risks and increasing impact of natural and other hazards especially in the developing world. Vulnerability, the potential for loss of life or property from disaster, has biophysical or social dimensions. Social vulnerability relates to societal attributes which has negative impacts on disaster outcomes. This study sought to develop a spatially explicit index of social vulnerability, thus addressing the dearth of research in this area in sub-Saharan Africa. Nineteen variables were identified covering various aspects. Descriptive analysis of these variables revealed high heterogeneity across the South West region of Nigeria for both the state and the local government areas (LGAs. Feature identification using correlation analysis identified six important variables. Factor analysis identified two dimensions, namely accessibility and socioeconomic conditions, from this subset. A social vulnerability index (SoVI showed that Ondo and Ekiti have more vulnerable LGAs than other states in the region. About 50% of the LGAs in Osun and Ogun have a relatively low social vulnerability. Distribution of the SoVI shows that there are great differences within states as well as across regions. Scores of population density, disability and poverty have a high margin of error in relation to mean state scores. The study showed that with a geographical information system there are opportunities to model social vulnerability and monitor its evolution and dynamics across the continent.

  9. Software-Defined Radio Global System for Mobile Communications Transmitter Development for Heterogeneous Network Vulnerability Testing

    Science.gov (United States)

    2013-12-01

    AbdelWahab, “ 2G / 3G Inter-RAT Handover Performance Analysis,” Second European Conference on Antennas and Propagation, pp. 1, 8, 11–16, Nov. 2007. [19] J...RADIO GLOBAL SYSTEM FOR MOBILE COMMUNICATIONS TRANSMITTER DEVELOPMENT FOR HETEROGENEOUS NETWORK VULNERABILITY TESTING by Carson C. McAbee... MOBILE COMMUNICATIONS TRANSMITTER DEVELOPMENT FOR HETEROGENEOUS NETWORK VULNERABILITY TESTING 5. FUNDING NUMBERS 6. AUTHOR(S) Carson C. McAbee

  10. Administration of secretin for autism alters dopamine metabolism in the central nervous system.

    Science.gov (United States)

    Toda, Yoshihiro; Mori, Kenji; Hashimoto, Toshiaki; Miyazaki, Masahito; Nozaki, Satoshi; Watanabe, Yasuyoshi; Kuroda, Yasuhiro; Kagami, Shoji

    2006-03-01

    We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.

  11. Vulnerability and risk of deltaic social-ecological systems exposed to multiple hazards.

    Science.gov (United States)

    Hagenlocher, Michael; Renaud, Fabrice G; Haas, Susanne; Sebesvari, Zita

    2018-08-01

    Coastal river deltas are hotspots of global change impacts. Sustainable delta futures are increasingly threatened due to rising hazard exposure combined with high vulnerabilities of deltaic social-ecological systems. While the need for integrated multi-hazard approaches has been clearly articulated, studies on vulnerability and risk in deltas either focus on local case studies or single hazards and do not apply a social-ecological systems perspective. As a result, vulnerabilities and risks in areas with strong social and ecological coupling, such as coastal deltas, are not fully understood and the identification of risk reduction and adaptation strategies are often based on incomplete assumptions. To overcome these limitations, we propose an innovative modular indicator library-based approach for the assessment of multi-hazard risk of social-ecological systems across and within coastal deltas globally, and apply it to the Amazon, Ganges-Brahmaputra-Meghna (GBM), and Mekong deltas. Results show that multi-hazard risk is highest in the GBM delta and lowest in the Amazon delta. The analysis reveals major differences between social and environmental vulnerability across the three deltas, notably in the Mekong and the GBM deltas where environmental vulnerability is significantly higher than social vulnerability. Hotspots and drivers of risk vary spatially, thus calling for spatially targeted risk reduction and adaptation strategies within the deltas. Ecosystems have been identified as both an important element at risk as well as an entry point for risk reduction and adaptation strategies. Copyright © 2018. Published by Elsevier B.V.

  12. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  13. Vulnerability Analysis of Soft Caving Tunnel Support System and Surrounding Rock Optimal Control Technology Research

    Directory of Open Access Journals (Sweden)

    Ming Ji

    2014-01-01

    Full Text Available The vulnerability assessment model, composed by 11 vulnerability factors, is established with the introduction of the concept of “vulnerability” into the assessment of tunnel support system. Analytic hierarchy process is utilized to divide these 11 factors into human attributes and natural attributes, and define the weight of these factors for the model. The “vulnerability” applied io the assessment of the tunnel support system model is reached. The vulnerability assessment model was used for evaluating and modifying the haulage tunnel #3207 of Bo-fang mine panel #2. The results decreased the vulnerability of the tunnel support system and demonstrated acceptable effects. Furthermore, the results show that the impact of human attributes on tunnel support systems is dramatic under the condition that natural attributes are permanent, and the “vulnerability” is exactly a notable factor to manifest the transformation during this process. The results also indicate that optimizing human attributes can attenuate vulnerability in tunnel support systems. As a result, enhancement of stability of tunnel support systems can be achieved.

  14. A Mamdani Adaptive Neural Fuzzy Inference System for Improvement of Groundwater Vulnerability.

    Science.gov (United States)

    Agoubi, Belgacem; Dabbaghi, Radhia; Kharroubi, Adel

    2018-01-23

    Assessing groundwater vulnerability is an important procedure for sustainable water management. Various methods have been developed for effective assessment of groundwater vulnerability and protection. However, each method has its own conditions of use and, in practice; it is difficult to return the same results for the same site. The research conceptualized and developed an improved DRASTIC method using Mamdani Adaptive Neural Fuzzy Inference System (M-ANFIS-DRASTIC). DRASTIC and M-ANFIS-DRASTIC were applied in the Jorf aquifer, southeastern Tunisia, and results were compared. Results confirm that M-ANFIS-DRASTIC combined with geostatistical tools is more powerful, generated more precise vulnerability classes with very low estimation variance. Fuzzy logic has a power to produce more realistic aquifer vulnerability assessments and introduces new ways of modeling in hydrogeology using natural human language expressed by logic rules. © 2018, National Ground Water Association.

  15. Vulnerabilities, Influences and Interaction Paths: Failure Data for Integrated System Risk Analysis

    Science.gov (United States)

    Malin, Jane T.; Fleming, Land

    2006-01-01

    We describe graph-based analysis methods for identifying and analyzing cross-subsystem interaction risks from subsystem connectivity information. By discovering external and remote influences that would be otherwise unexpected, these methods can support better communication among subsystem designers at points of potential conflict and to support design of more dependable and diagnosable systems. These methods identify hazard causes that can impact vulnerable functions or entities if propagated across interaction paths from the hazard source to the vulnerable target. The analysis can also assess combined impacts of And-Or trees of disabling influences. The analysis can use ratings of hazards and vulnerabilities to calculate cumulative measures of the severity and importance. Identification of cross-subsystem hazard-vulnerability pairs and propagation paths across subsystems will increase coverage of hazard and risk analysis and can indicate risk control and protection strategies.

  16. Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

    Directory of Open Access Journals (Sweden)

    Chen Yang

    Full Text Available High-voltage spindles (HVSs have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1 in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

  17. Development of an Audit Classification Index (ACI) for Federal E-Learning Systems Security Vulnerabilities

    Science.gov (United States)

    Johnson, Gerald D.

    2012-01-01

    As U.S federal government agencies have increased the use of the Internet to utilize technologies such as e-learning, U.S. federal government information systems have become more exposed to security vulnerabilities that may contribute to system attacks and system exploitation. U.S. federal government agencies are required to come up with their own…

  18. A probabilistic framework for assessing vulnerability to climate variability and change: The case of the US water supply system

    Science.gov (United States)

    Romano Foti; Jorge A. Ramirez; Thomas C. Brown

    2014-01-01

    We introduce a probabilistic framework for vulnerability analysis and use it to quantify current and future vulnerability of the US water supply system. We also determine the contributions of hydro-climatic and socio-economic drivers to the changes in projected vulnerability. For all scenarios and global climatemodels examined, the US Southwest including California and...

  19. Research on seal control systems for international nuclear safeguard and the vulnerability assessment on the seals

    International Nuclear Information System (INIS)

    Zhang Hongjian; Liu Tianshu; Cao Fangfang; Xu Chunyan

    2014-01-01

    Safeguard seals, also called Tamper-indicating devices (TIDs), are widely used to detect tampering or unauthorized entry in the international safeguard and security systems, Seal control systems consist of seal implementing plan, seal development and the vulnerability assessment on tbe seals, effective implementing procedures and methods of the seals. The vulnerability assessment contents of safeguard seals, thermo-shrinked film seals being as an example, and seals control systems in the implementation program are researched. The seal control systems discuss task assignment, seals management flow and seals program data flow to promote applying effectively seals. The vulnerability assessment program of seals studies assurance level to some different tampering techniques and measures. The researches must promote utilizing seals effectively for nuclear security, non-proliferation of nuclear weapons, radioactive waste management, and the nuclear material accounting and control. (authors)

  20. Distinct effects of ketamine and acetyl l-carnitine on the dopamine system in zebrafish

    Science.gov (United States)

    Robinson, Bonnie L.; Dumas, Melanie; Cuevas, Elvis; Gu, Qiang; Paule, Merle G.; Ali, Syed F.; Kanungo, Jyotshna

    2016-01-01

    Ketamine, a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1–0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reversed 2 mM ketamine-induced reduction in HVA levels. With ALCAR alone, the expression of genes encoding the DA metabolizing enzymes, MAO (monoamine oxidase) and catechol-O-methyltransferase (COMT), was not affected. However, ketamine altered MAO mRNA expression, except at the 0.1 mM dose. COMT transcripts were reduced in the 2 mM ketamine-treated group. These distinct effects of ketamine and ALCAR on the DA system may shed some light on the mechanism on how ketamine can work as an anti-depressant, especially at sub-anesthetic doses that do not affect DA metabolism and suppress MAO gene expression. PMID:26898327

  1. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

    Directory of Open Access Journals (Sweden)

    Elham A. Afify

    2017-11-01

    Full Text Available Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate, (visceral, acetic acid, and (inflammatory, formalin test in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively. The study revealed that propranolol (0.25–20 mg/Kg, IP administration did not produce analgesia in mice. However, 10 mg/Kg propranolol, enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1, and 2 mg/Kg, IP in the three nociceptive tests. It also shifted the dose response curve of morphine to the left. The combined effect of propranolol and morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP, and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP. Repeated daily administration of propranolol (10 mg/Kg, IP did not alter the nociceptive responses in the three pain tests, but it significantly potentiated morphine-induced antinociception in the hot plate, acetic acid-evoked writhing, and in the second phase of formalin tests. Together, the data suggest that a cross-talk exists between the opioidergic and adrenergic systems and implicate dopamine and GABA systems in this synergistic effect of morphine-propranolol combination. Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid analgesics.

  2. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

  3. Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

    Science.gov (United States)

    Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

    2016-03-01

    Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

  4. Effect of dopamine injection on the hemocyte count and prophenoloxidase system of the white shrimp Litopenaeus vannamei

    Science.gov (United States)

    Pan, Luqing; Hu, Fawen; Zheng, Debin

    2011-09-01

    Effects of dopamine injection on the hemocyte count, phenoloxidase activity, serine proteinase activity, proteinase inhibitor activity and α2-macroglobulin-like activity in L. vannamei were studied. Results showed that dopamine injection resulted in a significant effect on the parameters measured ( P < 0.05), while no significant difference was observed in the control group (0.85% NaCl). In the experimental groups, the hemocyte count reached the minimum in 3 h; granular and semi-granular cells became stable after 12 h and hyaline cells and the total hemocyte count became stable after 18 h. Phenoloxidase activity reached the minimum in 6 h, and then became stable after 9 h. Serine protease activity and proteinase inhibitor activity reached the minimum in 3 h, and α2-macroglobulin-like activity reached the maximum in 3 h, and all the three parameters became stable after 12 h. The results suggest that the activating mechanisms of the proPO system triggered by dopamine are different from those triggered by invasive agents or spontaneously activated under a normal physical condition.

  5. A support system for assessing local vulnerability to weather and climate

    Science.gov (United States)

    Coletti, Alex; Howe, Peter D.; Yarnal, Brent; Wood, Nathan J.

    2013-01-01

    The changing number and nature of weather- and climate-related natural hazards is causing more communities to need to assess their vulnerabilities. Vulnerability assessments, however, often require considerable expertise and resources that are not available or too expensive for many communities. To meet the need for an easy-to-use, cost-effective vulnerability assessment tool for communities, a prototype online vulnerability assessment support system was built and tested. This prototype tool guides users through a stakeholder-based vulnerability assessment that breaks the process into four easy-to-implement steps. Data sources are integrated in the online environment so that perceived risks—defined and prioritized qualitatively by users—can be compared and discussed against the impacts that past events have had on the community. The support system is limited in scope, and the locations of the case studies do not provide a sufficiently broad range of sample cases. The addition of more publically available hazard databases combined with future improvements in the support system architecture and software will expand opportunities for testing and fully implementing the support system.

  6. Dopamine and Stress System Modulation of Sex Differences in Decision Making.

    Science.gov (United States)

    Georgiou, Polymnia; Zanos, Panos; Bhat, Shambhu; Tracy, J Kathleen; Merchenthaler, Istvan J; McCarthy, Margaret M; Gould, Todd D

    2018-01-01

    Maladaptive decision making is associated with several neuropsychiatric disorders, including problem gambling and suicidal behavior. The prevalence of these disorders is higher in men vs women, suggesting gender-dependent regulation of their pathophysiology underpinnings. We assessed sex differences in decision making using the rat version of the Iowa gambling task. Female rats identified the most optimal choice from session 1, whereas male rats from session 5. Male, but not female rats, progressively improved their advantageous option responding and surpassed females. Estrus cycle phase did not affect decision making. To test whether pharmacological manipulations targeting the dopaminergic and stress systems affect decision making in a sex-dependent manner, male and female rats received injections of a dopamine D 2 receptor (D 2 R) antagonist (eticlopride), D 2 R agonist (quinpirole), corticotropin-releasing factor 1 (CRF 1 ) antagonist (antalarmin), and α 2 -adrenergic receptor antagonist (yohimbine; used as a pharmacological stressor). Alterations in mRNA levels of D 2 R and CRF 1 were also assessed. Eticlopride decreased advantageous responding in male, but not female rats, whereas quinpirole decreased advantageous responding specifically in females. Yohimbine dose-dependently decreased advantageous responding in female rats, whereas decreased advantageous responding was only observed at higher doses in males. Antalarmin increased optimal choice responding only in female rats. Higher Drd2 and Crhr1 expression in the amygdala were observed in female vs male rats. Higher amygdalar Crhr1 expression was negatively correlated with advantageous responding specifically in females. This study demonstrates the relevance of dopaminergic- and stress-dependent sex differences to maladaptive decision making.

  7. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress

    Science.gov (United States)

    2005-07-01

    K. (1995) Methamphetamine -induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents...glutamate receptors is protective against methamphetamine neurotoxicity . JNeurosci 22, 2135-2141. Beer R., Franz G., Srinivasan A., Hayes R. L., Pike B. R...1992) The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole

  8. Voluntary Exercise Improves Performance of a Discrimination Task through Effects on the Striatal Dopamine System

    Science.gov (United States)

    Eddy, Meghan C.; Stansfield, Katherine J.; Green, John T.

    2014-01-01

    We have previously demonstrated that voluntary exercise facilitates discrimination learning in a modified T-maze. There is evidence implicating the dorsolateral striatum (DLS) as the substrate for this task. The present experiments examined whether changes in DLS dopamine receptors might underlie the exercise-associated facilitation. Infusing a…

  9. ESB-Based Sensor Web Integration for the Prediction of Electric Power Supply System Vulnerability

    Science.gov (United States)

    Stoimenov, Leonid; Bogdanovic, Milos; Bogdanovic-Dinic, Sanja

    2013-01-01

    Electric power supply companies increasingly rely on enterprise IT systems to provide them with a comprehensive view of the state of the distribution network. Within a utility-wide network, enterprise IT systems collect data from various metering devices. Such data can be effectively used for the prediction of power supply network vulnerability. The purpose of this paper is to present the Enterprise Service Bus (ESB)-based Sensor Web integration solution that we have developed with the purpose of enabling prediction of power supply network vulnerability, in terms of a prediction of defect probability for a particular network element. We will give an example of its usage and demonstrate our vulnerability prediction model on data collected from two different power supply companies. The proposed solution is an extension of the GinisSense Sensor Web-based architecture for collecting, processing, analyzing, decision making and alerting based on the data received from heterogeneous data sources. In this case, GinisSense has been upgraded to be capable of operating in an ESB environment and combine Sensor Web and GIS technologies to enable prediction of electric power supply system vulnerability. Aside from electrical values, the proposed solution gathers ambient values from additional sensors installed in the existing power supply network infrastructure. GinisSense aggregates gathered data according to an adapted Omnibus data fusion model and applies decision-making logic on the aggregated data. Detected vulnerabilities are visualized to end-users through means of a specialized Web GIS application. PMID:23955435

  10. ESB-Based Sensor Web Integration for the Prediction of Electric Power Supply System Vulnerability

    Directory of Open Access Journals (Sweden)

    Milos Bogdanovic

    2013-08-01

    Full Text Available Electric power supply companies increasingly rely on enterprise IT systems to provide them with a comprehensive view of the state of the distribution network. Within a utility-wide network, enterprise IT systems collect data from various metering devices. Such data can be effectively used for the prediction of power supply network vulnerability. The purpose of this paper is to present the Enterprise Service Bus (ESB-based Sensor Web integration solution that we have developed with the purpose of enabling prediction of power supply network vulnerability, in terms of a prediction of defect probability for a particular network element. We will give an example of its usage and demonstrate our vulnerability prediction model on data collected from two different power supply companies. The proposed solution is an extension of the GinisSense Sensor Web-based architecture for collecting, processing, analyzing, decision making and alerting based on the data received from heterogeneous data sources. In this case, GinisSense has been upgraded to be capable of operating in an ESB environment and combine Sensor Web and GIS technologies to enable prediction of electric power supply system vulnerability. Aside from electrical values, the proposed solution gathers ambient values from additional sensors installed in the existing power supply network infrastructure. GinisSense aggregates gathered data according to an adapted Omnibus data fusion model and applies decision-making logic on the aggregated data. Detected vulnerabilities are visualized to end-users through means of a specialized Web GIS application.

  11. ESB-based Sensor Web integration for the prediction of electric power supply system vulnerability.

    Science.gov (United States)

    Stoimenov, Leonid; Bogdanovic, Milos; Bogdanovic-Dinic, Sanja

    2013-08-15

    Electric power supply companies increasingly rely on enterprise IT systems to provide them with a comprehensive view of the state of the distribution network. Within a utility-wide network, enterprise IT systems collect data from various metering devices. Such data can be effectively used for the prediction of power supply network vulnerability. The purpose of this paper is to present the Enterprise Service Bus (ESB)-based Sensor Web integration solution that we have developed with the purpose of enabling prediction of power supply network vulnerability, in terms of a prediction of defect probability for a particular network element. We will give an example of its usage and demonstrate our vulnerability prediction model on data collected from two different power supply companies. The proposed solution is an extension of the GinisSense Sensor Web-based architecture for collecting, processing, analyzing, decision making and alerting based on the data received from heterogeneous data sources. In this case, GinisSense has been upgraded to be capable of operating in an ESB environment and combine Sensor Web and GIS technologies to enable prediction of electric power supply system vulnerability. Aside from electrical values, the proposed solution gathers ambient values from additional sensors installed in the existing power supply network infrastructure. GinisSense aggregates gathered data according to an adapted Omnibus data fusion model and applies decision-making logic on the aggregated data. Detected vulnerabilities are visualized to end-users through means of a specialized Web GIS application.

  12. The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia.

    Science.gov (United States)

    Howes, Oliver D; McCutcheon, Robert; Owen, Michael J; Murray, Robin M

    2017-01-01

    The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia. Because it was initially based on indirect evidence and findings in patients with established schizophrenia, it was unclear what role dopamine played in the onset of the disorder. However, recent studies in people at risk of schizophrenia have found elevated striatal dopamine synthesis capacity and increased dopamine release to stress. Furthermore, striatal dopamine changes have been linked to altered cortical function during cognitive tasks, in line with preclinical evidence that a circuit involving cortical projections to the striatum and midbrain may underlie the striatal dopamine changes. Other studies have shown that a number of environmental risk factors for schizophrenia, such as social isolation and childhood trauma, also affect presynaptic dopaminergic function. Advances in preclinical work and genetics have begun to unravel the molecular architecture linking dopamine, psychosis, and psychosocial stress. Included among the many genes associated with risk of schizophrenia are the gene encoding the dopamine D 2 receptor and those involved in the upstream regulation of dopaminergic synthesis, through glutamatergic and gamma-aminobutyric acidergic pathways. A number of these pathways are also linked to the stress response. We review these new lines of evidence and present a model of how genes and environmental factors may sensitize the dopamine system so that it is vulnerable to acute stress, leading to progressive dysregulation and the onset of psychosis. Finally, we consider the implications for rational drug development, in particular regionally selective dopaminergic modulation, and the potential of genetic factors to stratify patients. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Vulnerability analysis on a VPN for a remote monitoring system

    International Nuclear Information System (INIS)

    Kim, Jung Soo; Kim, Jong Soo; Park, Il Jin; Min, Kyung Sik; Choi, Young Myung

    2004-01-01

    14 Pressurized Water Reactors(PWR) in Korea use a Remote Monitoring System(RMS), which have been in Korea Since 1998. A memorandum of understanding on remote monitoring, based on enhanced cooperation on PWRs, was signed at the 10th safeguards review meeting in October 2001 between the International Atomic Energy Agency(IAEA) and Ministry Of Science and Technology(MOST). Thereafter, all PWR power plants applied for remote monitoring systems. However, the existing method is high cost (involving expensive telephone costs). So, it was eventually applied to an internet system for remote monitoring. According to the internet-based Virtual Private Network(VPN) applied to remote monitoring, the Korea Atomic Energy Research Institute(KAERI) came to an agreement with the IAEA, using a Member State Support Program(MSSP). Phase I is a lab test. Phase II is to apply it to a target power plant. Phase III is to apply it to all the power plants. This paper reports on the penetration testing of phase I. Phase I involved both domestic testing and international testing. The target of the testing consisted of a Surveillance Digital Integrated system(SDIS) server, IAEA server and TCNC(Technology Center for Nuclear Control) server. In each system, Virtual Private Network(VPN) system hardware was installed. The penetration of the three systems and the three VPNs was tested. The domestic test involved two hacking scenarios: hacking from the outside and hacking from the inside. The international test involved one scenario from the outside. The results of tests demonstrated that the VPN hardware provided a good defense against hacking. We verified that there was no invasion of the system (SDIS server and VPN; TCNC server and VPN; and IAEA server and VPN) via penetration testing

  14. An Assessment of Vulnerabilities for Ship-based Control Systems

    Science.gov (United States)

    2009-09-01

    finance, emergency and government services, and agriculture. These systems are the lifeblood of the nation’s logistic , economic, and functional...considerable amounts of sewage into parks, rivers, and a hotel , causing severe environmental harm. His goal was apparently to be hired as a consultant to...same issue from occurring with outbound traffic. Second, there should restricted access from the enterprise network to the control system network

  15. Vulnerability analysis on a VPN for a remote monitoring system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Soo; Kim, Jong Soo; Park, Il Jin; Min, Kyung Sik; Choi, Young Myung [KAERI, Taejon (Korea, Republic of)

    2004-08-01

    14 Pressurized Water Reactors(PWR) in Korea use a Remote Monitoring System(RMS), which have been in Korea Since 1998. A memorandum of understanding on remote monitoring, based on enhanced cooperation on PWRs, was signed at the 10th safeguards review meeting in October 2001 between the International Atomic Energy Agency(IAEA) and Ministry Of Science and Technology(MOST). Thereafter, all PWR power plants applied for remote monitoring systems. However, the existing method is high cost (involving expensive telephone costs). So, it was eventually applied to an internet system for remote monitoring. According to the internet-based Virtual Private Network(VPN) applied to remote monitoring, the Korea Atomic Energy Research Institute(KAERI) came to an agreement with the IAEA, using a Member State Support Program(MSSP). Phase I is a lab test. Phase II is to apply it to a target power plant. Phase III is to apply it to all the power plants. This paper reports on the penetration testing of phase I. Phase I involved both domestic testing and international testing. The target of the testing consisted of a Surveillance Digital Integrated system(SDIS) server, IAEA server and TCNC(Technology Center for Nuclear Control) server. In each system, Virtual Private Network(VPN) system hardware was installed. The penetration of the three systems and the three VPNs was tested. The domestic test involved two hacking scenarios: hacking from the outside and hacking from the inside. The international test involved one scenario from the outside. The results of tests demonstrated that the VPN hardware provided a good defense against hacking. We verified that there was no invasion of the system (SDIS server and VPN; TCNC server and VPN; and IAEA server and VPN) via penetration testing.

  16. Power System Extreme Event Detection: The VulnerabilityFrontier

    Energy Technology Data Exchange (ETDEWEB)

    Lesieutre, Bernard C.; Pinar, Ali; Roy, Sandip

    2007-10-17

    In this work we apply graph theoretic tools to provide aclose bound on a frontier relating the number of line outages in a gridto the power disrupted by the outages. This frontier describes theboundary of a space relating the possible severity of a disturbance interms of power disruption, from zero to some maximum on the boundary, tothe number line outages involved in the event. We present the usefulnessof this analysis with a complete analysis of a 30 bus system, and presentresults for larger systems.

  17. Web based remote monitoring and controlling system for vulnerable environments

    Science.gov (United States)

    Thomas, Aparna; George, Minu

    2016-03-01

    The two major areas of concern in industrial establishments are monitoring and security. The remote monitoring and controlling can be established with the help of Web technology. Managers can monitor and control the equipment in the remote area through a web browser. The targeted area includes all type of susceptible environment like gas filling station, research and development laboratories. The environmental parameters like temperature, light intensity, gas etc. can be monitored. Security is a very important factor in an industrial setup. So motion detection feature is added to the system to ensure the security. The remote monitoring and controlling system makes use of the latest, less power consumptive and fast working microcontroller like S3C2440. This system is based on ARM9 and Linux operating system. The ARM9 will collect the sensor data and establish real time video monitoring along with motion detection feature. These captured video data as well as environmental data is transmitted over internet using embedded web server which is integrated within the ARM9 board.

  18. Macro-Prudential Policies to Mitigate Financial System Vulnerabilities

    NARCIS (Netherlands)

    Claessens, S.; Ghosh, S.R.; Mihet, R.

    2014-01-01

    Macro-prudential policies aimed at mitigating systemic financial risks have become part of the policy toolkit in many emerging markets and some advanced countries. Their effectiveness and efficacy are not well-known, however. Using panel data regressions, we analyze how changes in balance sheets of

  19. Vulnerability of semi-enclosed marine systems to environmental disturbances

    Digital Repository Service at National Institute of Oceanography (India)

    MacCracken, M.; Escobar-Briones, E; Gilbert, D.; Korotaev, G.; Naqvi, S.W.A.; Perillo, G.M.E; Rixen, T.; Stanev, E; Sundby, B.; Thomas, H.; Unger, D.; Urban, E

    Semi-Enclosed Marine Systems to Environmental Disturbances Michael MacCracken t Elva Escobar-Briones t Denis Gilbert, Gennady Korotaev, Wajih Naqvi, Gerardo M.E. Perillo, Tim Rixen, Emil Stanev, Bj0rn Sundby, Helmuth Thomas t Daniela Unger, and Edward R. Urban, Jr...

  20. Social Vulnerability to Natural Hazards in Urban Systems. An Application in Santo Domingo (Dominican Republic

    Directory of Open Access Journals (Sweden)

    Eleonora Giovene di Girasole

    2017-11-01

    Full Text Available The concept of risk has become increasingly complex, and has been used not only in relation to the natural features of a region, but also to its socio-economic context. In this conceptualization, the latter directly influences the capacity of a community to cope with, recover from, and adapt to natural hazards. Conceiving vulnerability as a measure of a socio-ecological system’s resilience, and at the same time, as a multidimensional variable that changes in space and time, makes the study of the different ways in which natural hazards impact on society all the more urgent. This is particularly true for developing countries, where risk related to natural hazards affects populations and areas that must deal with stress conditions, such as humanitarian, social and military emergencies. This article presents a methodology for the analysis of social vulnerability, defined and experimented in the context of the international cooperation project “Estudio de la amenaza sísmica y vulnerabilidad física del Gran Santo Domingo”. The methodology, implemented through the employment of a Geographic Information System, led to the elaboration of a “Social Vulnerability Index” and a “Social Vulnerability Map”. These seek to describe the current condition of vulnerability of the city of Santo Domingo de Guzmán (Distrito Nacional in the Dominican Republic (DR, and are used to define context-related vulnerability scenarios, as well as to indicate the adequate set of mitigation objectives and actions. The results highlight the importance of using social vulnerability study as the point of departure for defining seismic-risk mitigation policies, emergency management, and territorial planning in order to reduce the impacts of disasters.

  1. The impact of high penetration of wind energy on the vulnerability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    EL-Arroudi, K.; Joos, G.; McGillis, D. [McGill Univ., Montreal, PQ (Canada). Dept. of Electrical and Computer Engineering

    2006-07-01

    This paper examined the impact of higher penetrations of wind energy installations on the vulnerability of power systems. Vulnerability was defined in terms of migration of system states based on the contingencies that might occur. It was noted that both the penetration levels and physical locations of wind energy installations in power systems have a strong influence on system vulnerability. A methodology was proposed to analyze the impacts of wind energy on power system vulnerability through the construction of a decision-tree classification model at the point of common coupling (PCC) bus. The aim of the model was to determine planning criteria for wind power interconnection and to ensure that design concepts are adequate and secure. The model was built by simulating a pre-specified range of system contingencies to generate patterns at the PCC bus. Actual measurements were then compared against known patterns, from which the stress levels of disturbances were estimated. Stress levels were defined in terms of the performance level measures delineated by National Electricity Reliability Council (NERC) planning standards. The methodology is a non-parametric learning technique able to produce classifiers about given problems in order to deduce information from new, unobserved cases. A case study consisting of a 4-machine system with a total generation of 2295 MW was presented where wind-based generation accounted for 450 MW. The decision-tree classifier was constructed by simulating 120 events generated by combinations of contingencies; seasonal wind patterns and different wind production levels per season. Results showed that with a knowledge of the total penetration level and location of wind power installations, it is possible to estimate the effect of wind energy on the vulnerability of a power system. 12 refs., 6 figs.

  2. Using HFACS-Healthcare to Identify Systemic Vulnerabilities During Surgery.

    Science.gov (United States)

    Cohen, Tara N; Francis, Sarah E; Wiegmann, Douglas A; Shappell, Scott A; Gewertz, Bruce L

    2018-03-01

    The Human Factors Analysis and Classification System for Healthcare (HFACS-Healthcare) was used to classify surgical near miss events reported via a hospital's event reporting system over the course of 1 year. Two trained analysts identified causal factors within each event narrative and subsequently categorized the events using HFACS-Healthcare. Of 910 original events, 592 could be analyzed further using HFACS-Healthcare, resulting in the identification of 726 causal factors. Most issues (n = 436, 60.00%) involved preconditions for unsafe acts, followed by unsafe acts (n = 257, 35.39%), organizational influences (n = 27, 3.72%), and supervisory factors (n = 6, 0.82%). These findings go beyond the traditional methods of trending incident data that typically focus on documenting the frequency of their occurrence. Analyzing near misses based on their underlying contributing human factors affords a greater opportunity to develop process improvements to reduce reoccurrence and better provide patient safety approaches.

  3. Regional Water System Vulnerabilities and Strengths for Unavoidable Climate Adaptation

    Science.gov (United States)

    Gleick, P. H.; Palaniappan, M.; Christian-Smith, J.; Cooley, H.

    2011-12-01

    A wide range of options are available to help water systems prepare and adapt for unavoidable climate impacts, but these options vary depending on region, climatic conditions, economic status, and technical infrastructure in place. Drawing on case studies from the United States, India, and elsewhere, and from both urban and agricultural water systems, risks to water supply and quality are evaluated and summarized and categories of responses to help improve the effectiveness of adaptation policies are reviewed. Among the issues to be discussed are characteristics unique to developing country cities, such as the predominance of informal actors in the water sector. The formal, or government sector, which often exclusively manages water access and distribution in developed country cities, is only one among many players in the water sector in developing country cities. Informal access to water includes direct access by individuals through private groundwater systems, private water markets using vendors or sales of bottled water, and rainwater harvesting systems on individual homes. In this environment, with already existing pressures on water availability and use, the impacts of climate change on water will be strongly felt. This complicates planning for water supply and demand and risks increasing already prevalent water insecurity, especially for urban poor. In wealthier countries, any planning for water-related climate impacts tends to take the form of "business as usual" responses, such as efforts to expand supply with new infrastructure, manage demand through conservation programs, or simply put off addressing the problem to the next generation of managers and users. These approaches can be effective, but also risk missing unusual, non-linear, or threshold impacts. Examples of more informed and innovative efforts to substantively address climate change risks will be presented.

  4. Workshop Builds Strategies to Address Global Positioning System Vulnerabilities

    Science.gov (United States)

    Fisher, Genene

    2011-01-01

    When we examine the impacts of space weather on society, do we really understand the risks? Can past experiences reliably predict what will happen in the future? As the complexity of technology increases, there is the potential for it to become more fragile, allowing for a single point of failure to bring down the entire system. Take the Global Positioning System (GPS) as an example. GPS positioning, navigation, and timing have become an integral part of daily life, supporting transportation and communications systems vital to the aviation, merchant marine, cargo, cellular phone, surveying, and oil exploration industries. Everyday activities such as banking, mobile phone operations, and even the control of power grids are facilitated by the accurate timing provided by GPS. Understanding the risks of space weather to GPS and the many economic sectors reliant upon it, as well as how to build resilience, was the focus of a policy workshop organized by the American Meteorological Society (AMS) and held on 13-14 October 2010 in Washington, D. C. The workshop brought together a select group of policy makers, space weather scientists, and GPS experts and users.

  5. Vulnerability and adaptation to climate variability and change in smallholder farming systems in Zimbabwe

    NARCIS (Netherlands)

    Rurinda, J.

    2014-01-01

    Keywords: Climate change; Increased climate variability; Vulnerability; Smallholder farmers; Adaptation

    Climate change and increased climate variability are currently seen as the major constraints to the already stressed smallholder farming livelihood system in

  6. Critical location identification and vulnerability analysis of interdependent infrastructure systems under spatially localized attacks

    International Nuclear Information System (INIS)

    Ouyang, Min

    2016-01-01

    Infrastructure systems are usually spatially distributed in a wide area and are subject to many types of hazards. For each type of hazards, modeling their direct impact on infrastructure components and analyzing their induced system-level vulnerability are important for identifying mitigation strategies. This paper mainly studies spatially localized attacks that a set of infrastructure components located within or crossing a circle shaped spatially localized area is subject to damage while other components do not directly fail. For this type of attacks, taking interdependent power and gas systems in Harris County, Texas, USA as an example, this paper proposes an approach to exactly identify critical locations in interdependent infrastructure systems and make pertinent vulnerability analysis. Results show that (a) infrastructure interdependencies and attack radius largely affect the position of critical locations; (b) spatially localized attacks cause less vulnerability than equivalent random failures; (c) in most values of attack radius critical locations identified by considering only node failures do not change when considering both node and edge failures in the attack area; (d) for many values of attack radius critical locations identified by topology-based model are also critical from the flow-based perspective. - Highlights: • We propose a method to identify critical locations in interdependent infrastructures. • Geographical interdependencies and attack radius largely affect critical locations. • Localized attacks cause less vulnerability than equivalent random failures. • Whether considering both node and edge failures affects critical locations. • Topology-based critical locations are also critical from flow-based perspective.

  7. Safety, mobility and comfort assessment methodologies of intelligent transport systems for vulnerable road users

    NARCIS (Netherlands)

    Malone, K.; Silla, A.; Johanssen, C.; Bell, D.

    2017-01-01

    Introduction: This paper describes the modification and development of methodologies to assess the impacts of Intelligent Transport Systems (ITS) applications for Vulnerable Road users (VRUs) in the domains of safety, mobility and comfort. This effort was carried out in the context of the VRUITS

  8. Reliability and vulnerability analyses of critical infrastructures: Comparing two approaches in the context of power systems

    International Nuclear Information System (INIS)

    Johansson, Jonas; Hassel, Henrik; Zio, Enrico

    2013-01-01

    Society depends on services provided by critical infrastructures, and hence it is important that they are reliable and robust. Two main approaches for gaining knowledge required for designing and improving critical infrastructures are reliability analysis and vulnerability analysis. The former analyses the ability of the system to perform its intended function; the latter analyses its inability to withstand strains and the effects of the consequent failures. The two approaches have similarities but also some differences with respect to what type of information they generate about the system. In this view, the main purpose of this paper is to discuss and contrast these approaches. To strengthen the discussion and exemplify its findings, a Monte Carlo-based reliability analysis and a vulnerability analysis are considered in their application to a relatively simple, but representative, system the IEEE RTS96 electric power test system. The exemplification reveals that reliability analysis provides a good picture of the system likely behaviour, but fails to capture a large portion of the high consequence scenarios, which are instead captured in the vulnerability analysis. Although these scenarios might be estimated to have small probabilities of occurrence, they should be identified, considered and treated cautiously, as probabilistic analyses should not be the only input to decision-making for the design and protection of critical infrastructures. The general conclusion that can be drawn from the findings of the example is that vulnerability analysis should be used to complement reliability studies, as well as other forms of probabilistic risk analysis. Measures should be sought for reducing both the vulnerability, i.e. improving the system ability to withstand strains and stresses, and the reliability, i.e. improving the likely behaviour

  9. Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice

    OpenAIRE

    Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

    2005-01-01

    Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized that blockade of D2 receptors might facilitate extinction in mice, while agonists should block extinction, as they do in rats. One day after fear con...

  10. Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain.

    Science.gov (United States)

    Sinclair, Duncan; Purves-Tyson, Tertia D; Allen, Katherine M; Weickert, Cynthia Shannon

    2014-04-01

    Adolescence is a developmental period of complex neurobiological change and heightened vulnerability to psychiatric illness. As a result, understanding factors such as sex and stress hormones which drive brain changes in adolescence, and how these factors may influence key neurotransmitter systems implicated in psychiatric illness, is paramount. In this review, we outline the impact of sex and stress hormones at adolescence on dopamine neurotransmission, a signaling pathway which is critical to healthy brain function and has been implicated in psychiatric illness. We review normative developmental changes in dopamine, sex hormone, and stress hormone signaling during adolescence and throughout postnatal life, then highlight the interaction of sex and stress hormones and review their impacts on dopamine neurotransmission in the adolescent brain. Adolescence is a time of increased responsiveness to sex and stress hormones, during which the maturing dopaminergic neural circuitry is profoundly influenced by these factors. Testosterone, estrogen, and glucocorticoids interact with each other and have distinct, brain region-specific impacts on dopamine neurotransmission in the adolescent brain, shaping brain maturation and cognitive function in adolescence and adulthood. Some effects of stress/sex hormones on cortical and subcortical dopamine parameters bear similarities with dopaminergic abnormalities seen in schizophrenia, suggesting a possible role for sex/stress hormones at adolescence in influencing risk for psychiatric illness via modulation of dopamine neurotransmission. Stress and sex hormones may prove useful targets in future strategies for modifying risk for psychiatric illness.

  11. ETUDE FONCTIONNELLE DES SYSTEMES DE CAPTURE SYNAPTOSOMALE ET VESICULAIRE DE DOPAMINE

    Directory of Open Access Journals (Sweden)

    M SLIMANI

    2001-06-01

    Full Text Available L‘injection stéréotaxique unilatérale dans la substance noire de la 6 hydroxy-dopamine ( 6OH-DA se traduit par une chute  parallèle  de  la   capture de dopamine tritiée au  niveau  synaptosomale de  l'ordre  de -70 % et dans les préparations vésiculaires de l'ordre de -69 %, comparées aux préparations issues de Rats non lésés. Ces résultats montrent que ces deux préparations synaptosomales et vésiculaires sont bien d'origine dopaminergique. D'autre part, une étude comparative de l'effet de quelques agents pharmacologiques (β carbolines, imipraminiques, amphétamine et les inhibiteurs purs de la capture synaptosomale sur la capture synaptosomale et vésiculaire de la dopamine tritiée in-vitro, montre qu'ils agissent comme de puissants inhibiteurs. Nous montrons également que le transporteur vésiculaire diffère du transporteur synaptosomal par sa stéréospécificité et sa sensibilité aux agents pharmacologiques.

  12. Different loss of dopamine transporter according to subtype of multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Won [Keimyung University Dongsan Medical Center, Department of Nuclear Medicine, Daegu (Korea, Republic of); Keimyung University, Department of Nuclear Medicine, School of Medicine, Jung-gu, Daegu (Korea, Republic of); Kim, Jae Seung; Oh, Minyoung; Oh, Jungsu S.; Lee, Sang Joo; Oh, Seung Jun [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Chung, Sun Ju; Lee, Chong Sik [University of Ulsan College of Medicine, Department of Neurology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-03-15

    The aim of this study was to evaluate whether striatal dopamine transporter (DAT) loss as measured by {sup 18}F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane ([{sup 18}F]FP-CIT) PET differs according to the metabolic subtype of multiple system atrophy (MSA) as assessed by [{sup 18}F]FDG PET. This retrospective study included 50 patients with clinically diagnosed MSA who underwent [{sup 18}F]FP-CIT and [{sup 18}F]FDG brain PET scans. The PET images were analysed using 12 striatal subregional volume-of-interest templates (bilateral ventral striatum, anterior caudate, posterior caudate, anterior putamen, posterior putamen, and ventral putamen). The patients were classified into three metabolic subtypes according to the [{sup 18}F]FDG PET findings: MSA-P{sub m} (striatal hypometabolism only), MSA-mixed{sub m} (both striatal and cerebellar hypometabolism), and MSA-C{sub m} (cerebellar hypometabolism only). The subregional glucose metabolic ratio (MR{sub gluc}), subregional DAT binding ratio (BR{sub DAT}), and intersubregional ratio (ISR{sub DAT}; defined as the BR{sub DAT} ratio of one striatal subregion to that of another striatal subregion) were compared according to metabolic subtype. Of the 50 patients, 13 presented with MSA-P{sub m}, 16 presented with MSA-mixed{sub m}, and 21 presented with MSA-C{sub m}. The BR{sub DAT} of all striatal subregions in the MSA-P{sub m} and MSA-mixed{sub m} groups were significantly lower than those in the MSA-C{sub m} group. The posterior putamen/anterior putamen ISR{sub DAT} and anterior putamen/ventral striatum ISR{sub DAT} in the MSA-P{sub m} and MSA-mixed{sub m} groups were significantly lower than those in the MSA-C{sub m} group. Patients with MSA-P{sub m} and MSA-mixed{sub m} showed more severe DAT loss in the striatum than patients with MSA-C{sub m}. Patients with MSA-C{sub m} had more diffuse DAT loss than patients with MSA-P{sub m} and MSA-mixed{sub m}. (orig.)

  13. THE DETERMINANTS OF BANKING SYSTEM VULNERABILITY IN THE REPUBLIC OF MOLDOVA

    Directory of Open Access Journals (Sweden)

    Dorina CLICHICI

    2013-12-01

    Full Text Available A banking system is more vulnerable when there are felt more negative effects on this as a consequence of the global financial crisis events. In the context of the objective of enhancing financial stability and, in particular, limiting the likelihood of failure of the banking system it is useful to verify how the main characteristics which play a role for banking system vulnerability behaved in the case of the Republic of Moldova: system’s liquidity, capitalization, competition, diversification, presence of foreign banks, and wholesale funding. In order to determine how hard was hit the banking system of Moldova by the recent financial crisis in the article are analyzed quantitative and qualitative the above mentioned characteristics and identified the crisis effects on them.

  14. Island Partition of Distribution System with Distributed Generators Considering Protection of Vulnerable Nodes

    Directory of Open Access Journals (Sweden)

    Gang Xu

    2017-10-01

    Full Text Available To improve the reliability of power supply in the case of the fault of distribution system with multiple distributed generators (DGs and reduce the influence of node voltage fluctuation on the stability of distribution system operation in power restoration, this paper proposes an island partition strategy of the distribution system considering the protection of vulnerable nodes. First of all, the electrical coupling coefficient of neighboring nodes is put forward according to distribution system topology and equivalent electrical impedance, and the power-dependence relationship between neighboring nodes is calculated based on the direction and level of the power flow between nodes. Then, the bidirectional transmission of the coupling features of neighboring nodes is realized through the modified PageRank algorithm, thus identifying the vulnerable nodes that have a large influence on the stability of distribution system operation. Next, combining the index of node vulnerability, an island partition model is constructed with the restoration of important loads as the primary goal. In addition, the mutually exclusive firefly algorithm (MEFA is also proposed to realize the interaction of learning and competition among fireflies, thus enhancing the globally optimal solution search ability of the algorithm proposed. The proposed island partition method is verified with a Pacific Gas and Electric Company (PG and E 60-node test system. Comparison with other methods demonstrates that the new method is feasible for the distribution system with multiple types of distributed generations and valid to enhance the stability and safety of the grid with a relatively power restoration ratio.

  15. Vulnerability Analysis for Physical Protection System at Hypothetical Facility of a Different Type Reactor

    International Nuclear Information System (INIS)

    Jung, Won-Moog; Kim, Jung-Soo; Kim, Jae-Kwang; Yoo, Ho-Sik; Kwak, Sung-Ho; Jang, Sung-Soon

    2007-01-01

    Since the 9/11 event in the U.S.A, International terror possibilities has been increased for nuclear facilities including nuclear power plants(NPPs). It is necessary to evaluate the performance of an existing physical protection system(PPS) at nuclear facilities based on such malevolent acts. Detection, delay, and response elements are all important to PPS. They are used for the analysis and evaluation of a PPS and its effectiveness. Methods are available to analyze a PPS and evaluate its effectiveness. Sandia National Laboratory(SNL) in the U.S.A developed a System Analysis of Vulnerability to Intrusion (SAVI) computer code for evaluating the effectiveness of PPS against outsider threats. This study presents the vulnerability analysis of the PPS at hypothetical facility of a different type using SAVI code that the basic input parameters are from PPS of a different type. For analysis, first, the site-specific Adversary Sequence Diagrams(ASDs) of the PPS is designed. It helps to understand the functions of the existing PPS composed of physical areas and Protection Elements(PEs). Then, the most vulnerable path of an ASD as a measure of effectiveness is determined. The results in the analysis can compare with the most vulnerable paths at a different type

  16. Systemic Vulnerabilities

    Science.gov (United States)

    2014-10-01

    CRm CAL FA~WR£S Q I • Software Engineering Institute I Ccamt>gw l\\~llon Lniwndty 34 Basic attack tree Destroy Building Generate Sufficient...by computer-security company marketing literature that touts 11hacker proof software,11 11triple-DES security,11 and the like. In truth, unbreakable

  17. Bioinspired near-infrared-excited sensing platform for in vitro antioxidant capacity assay based on upconversion nanoparticles and a dopamine-melanin hybrid system.

    Science.gov (United States)

    Wang, Dong; Chen, Chuan; Ke, Xuebin; Kang, Ning; Shen, Yuqing; Liu, Yongliang; Zhou, Xi; Wang, Hongjun; Chen, Changqing; Ren, Lei

    2015-02-11

    A novel core-shell structure based on upconversion fluorescent nanoparticles (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant capacity of biological fluids. In this approach, dopamine-melanin nanoshells facilely formed on the surface of UCNPs act as ultraefficient quenchers for upconversion fluorescence, contributing to a photoinduced electron-transfer mechanism. This spontaneous oxidative polymerization of the dopamine-induced quenching effect could be effectively prevented by the presence of various antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great selectivity and sensitivity toward antioxidants relative to other compounds at 100-fold higher concentration. A satisfactory correlation was established between the ratio of the "anti-quenching" fluorescence intensity and the concentration of antioxidants. Besides the response of the upconversion fluorescence signal, a specific evaluation process for antioxidants could be visualized by the color change from colorless to dark gray accompanied by the spontaneous oxidation of dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay platform was further used to evaluate the antioxidant capacity of cell extracts and human plasma, and satisfactory sensitivity, repeatability, and recovery rate were obtained. This approach features easy preparation, fluorescence/visual dual mode detection, high specificity to antioxidants, and enhanced sensitivity with NIR excitation, showing great potential for screening and quantitative evaluation of antioxidants in biological systems.

  18. Vulnerability of social-ecological system to climate change in Mongolia

    Science.gov (United States)

    Kakinuma, K.; Yanagawa, A.; Sasaki, T.; Kanae, S.

    2017-12-01

    Coping with future climate changes are one of the most important issues in the world. IPCC (2014) suggested that vulnerability and exposure of social-ecological systems to extreme climatic events (hazard) determine the impact of climate changes. Although the schematic framework is widely accepted, there are high uncertainty of vulnerability of social and ecological systems and it makes difficult to examine it in empirical researches. Our objective is to assess the climate change impact on the social-ecological system in Mongolia. We review researches about trends of climate (Hazard), vegetation, pastoral mobility (Vulnerability) and livestock distribution (Exposure) across Mongolia Climate trends are critical for last several decades and thus hazard may be increasing in Mongolia. Temperature is increasing with high confidence in all regions. Precipitation are slightly decreasing with medium confidence across the country, especially in northern and central regions. Exposure would also be increasing especially in northern, central and western regions, because livestock population are concentrating these regions after 1990. Generally, less productive ecosystems (e.g. few plant productivity and less species richness) are vulnerable to extreme climatic events such as drought. In that sense, southern region may be more vulnerable to climate changes than other regions. However, if we focus on pastoral mobility forms for drought, we get contractive conclusions. Pastoralists in southern region keep mobility to variable and scarce vegetation while pastoralists in northern region less mobile because of stable and much vegetation. Exclusive managements in northern region is able to maximized the number of livestock only under stable precipitation regimes. But at the same time, it is difficult to escape from hazardous areas when it is drought. Thus, in term of rangeland management, northern region would be more vulnerable to increase of drought intensity. Although northern and

  19. The role of genes, stress and dopamine in the development of schizophrenia

    Science.gov (United States)

    Howes, Oliver D; McCutcheon, Robert; Owen, Michael J; Murray, Robin

    2017-01-01

    The dopamine hypothesis is the longest standing pathoaetiological theory of schizophrenia. As it was initially based on indirect evidence and findings in patients with established schizophrenia it was unclear what role dopamine played in the onset of the disorder. However, recent studies in people at risk of schizophrenia have found elevated striatal dopamine synthesis capacity, and increased dopamine release to stress. Furthermore, striatal dopamine changes have been linked to altered cortical function during cognitive tasks, in-line with preclinical evidence that a circuit involving cortical projections to the striatum and midbrain may underlie the striatal dopamine changes. Other studies have shown that a number of environmental risk factors for schizophrenia, such as social isolation and childhood trauma, also impact on presynaptic dopaminergic function. Advances in preclinical work and genetics have begun to unravel the molecular architecture linking dopamine, psychosis and psychosocial stress. Included among the many genes associated with risk of schizophrenia, are the gene encoding the DRD2 receptor and those involved in the up-stream regulation of dopaminergic synthesis, through glutamatergic and gamma-aminobutyric acid (GABA)-ergic pathways. A number of these pathways are also linked to the stress response. We review these new lines of evidence and present a model of how genes and environmental factors may sensitise the dopamine system so that it is vulnerable to acute stress, leading to progressive dysregulation and the onset of psychosis. Finally, we consider the implications for rational drug development, in particular regionally selective dopaminergic modulation, and the potential of genetic factors to stratify patients. PMID:27720198

  20. A study of PLC system vulnerability checklists in nuclear power plants

    International Nuclear Information System (INIS)

    Cha, Ki Jong; Cho, Gi Ho; Ahn, Jaeh Young; Kim, Young Mi; Kwon, Yong Il

    2012-01-01

    Because the design of the PLCs (Programmable Logic Controller) in the I and C (Instrument and Control) systems for NPP (Nuclear Power Plant) were carried out independently, the problems of cyber security were not addressed in the PLC system designs. Recently, the analysis and the countermeasure development for the PLC systems became mandatory due to the developments in cyber attack techniques and the increasingly revealed vulnerability to such attacks. A comparative analysis on the cyber security checklist of PLC in industry control system and in NPP systems was carried out, and in this paper, the cyber security regulatory trend and the PLC usage status are described

  1. A study of PLC system vulnerability checklists in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Ki Jong; Cho, Gi Ho; Ahn, Jaeh Young [Convergence technology Research Commercialization Center, Daejeon (Korea, Republic of); Kim, Young Mi; Kwon, Yong Il [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2012-10-15

    Because the design of the PLCs (Programmable Logic Controller) in the I and C (Instrument and Control) systems for NPP (Nuclear Power Plant) were carried out independently, the problems of cyber security were not addressed in the PLC system designs. Recently, the analysis and the countermeasure development for the PLC systems became mandatory due to the developments in cyber attack techniques and the increasingly revealed vulnerability to such attacks. A comparative analysis on the cyber security checklist of PLC in industry control system and in NPP systems was carried out, and in this paper, the cyber security regulatory trend and the PLC usage status are described.

  2. Paraquat affects mitochondrial bioenergetics, dopamine system expression, and locomotor activity in zebrafish (Danio rerio).

    Science.gov (United States)

    Wang, Xiao H; Souders, Christopher L; Zhao, Yuan H; Martyniuk, Christopher J

    2018-01-01

    The dipyridyl herbicide paraquat induces oxidative stress in cells and is implicated in adult neurodegenerative diseases. However, less is known about paraquat toxicity in early stages of vertebrate development. To address this gap, zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 μM paraquat for 96 h. Paraquat did not induce significant mortality nor deformity in embryos and larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial respiration was related to earlier hatch times, oxygen consumption rate was measured in whole embryos. Maximal respiration of embryos exposed to 100 μM paraquat for 24 h was reduced by more than 70%, suggesting that paraquat negatively impacts mitochondrial bioenergetics in early development. Based upon this evidence for mitochondrial dysfunction, transcriptional responses of oxidative stress- and apoptosis-related genes were measured. Fish exposed to 1 μM paraquat showed higher expression levels of superoxide dismutase 2, heat shock protein 70, Bcl-2-associated X protein, and B-cell CLL/lymphoma 2a compared to control fish. No differences among groups were detected in larvae exposed to 10 and 100 μM paraquat, suggesting a non-monotonic response. We also measured endpoints related to larval behavior and dopaminergic signaling as paraquat is associated with degeneration of dopamine neurons. Locomotor activity was stimulated with 100 μM paraquat and dopamine transporter and dopamine receptor 3 mRNA levels were increased in larvae exposed to 1 μM paraquat, interpreted to be a compensatory response at lower concentrations. This study improves mechanistic understanding into the toxic actions of paraquat on early developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Vulnerable Genders, Vulnerable Loves

    DEFF Research Database (Denmark)

    Schleicher, Marianne

    2015-01-01

    This chapter analyses religious reflections on vulnerable genders and vulnerable loves from the Hebrew Bible to early Rabbinic literature. It is based on theories by inter alia Donna Haraway on complex identities, Turner and Maryanski on love as a prerequisite for survival, Michel Foucault...... on gathering knowledge and its often unpremeditated effect of recognition and inclusion, and Judith Butler on cultural intelligibility and subversion from within. With these theories as a departing point for the analysis, the chapter links the vulnerability of complex identities with the vulnerability...... of cultures which leads to the overall understanding that culture can accommodate complex identities associated with individual and cultural vulnerability as long as the overall survival of the culture is not threatened. This understanding questions the feasibility of the ethical position of thinkers...

  4. Design of a multi-dopamine-modified polymer ligand optimally suited for interfacing magnetic nanoparticles with biological systems.

    Science.gov (United States)

    Wang, Wentao; Ji, Xin; Na, Hyon Bin; Safi, Malak; Smith, Alexandra; Palui, Goutam; Perez, J Manuel; Mattoussi, Hedi

    2014-06-03

    We have designed a set of multifunctional and multicoordinating polymer ligands that are optimally suited for surface functionalizing iron oxide and potentially other magnetic nanoparticles (NPs) and promoting their integration into biological systems. The amphiphilic polymers are prepared by coupling (via nucleophilic addition) several amine-terminated dopamine anchoring groups, poly(ethylene glycol) moieties, and reactive groups onto a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. This design greatly benefits from the highly efficient and reagent-free one-step reaction of maleic anhydride groups with amine-containing molecules. The availability of several dopamine groups in the same ligand greatly enhances the ligand affinity, via multiple coordination, to the magnetic NPs, while the hydrophilic and reactive groups promote colloidal stability in buffer media and allow subsequent conjugation with target biomolecules. Iron oxide nanoparticles ligand exchanged with these polymer ligands have a compact hydrodynamic size and exhibit enhanced long-term colloidal stability over the pH range of 4-12 and in the presence of excess electrolytes. Nanoparticles ligated with terminally reactive polymers have been easily coupled to target dyes and tested in live cell imaging with no measurable cytotoxicity. Finally, the resulting hydrophilic nanoparticles exhibit large and size-dependent r2 relaxivity values.

  5. Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats

    Directory of Open Access Journals (Sweden)

    Toshikatsu Okumura

    2016-02-01

    Subcutaneously (80 mg/rat or intracisternally (2.5 μg/rat administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.

  6. Dopamine synthesis in alcohol drinking-prone and -resistant mouse strains

    Science.gov (United States)

    Siciliano, Cody A.; Locke, Jason L.; Mathews, Tiffany A.; Lopez, Marcelo F.; Becker, Howard C.; Jones, Sara R.

    2017-01-01

    Alcoholism is a prevalent and debilitating neuropsychiatric disease, and much effort has been aimed at elucidating the neurobiological mechanisms underlying maladaptive alcohol drinking in an effort to design rational treatment strategies. In preclinical literature, the use of inbred mouse lines has allowed for the examination of ethanol effects across vulnerable and resistant phenotypes. C57BL/6J mice consistently show higher rates of ethanol drinking compared to most mouse strains. Conversely, DBA/2J mice display low rates of ethanol consumption. Given that the reinforcing and rewarding effects of ethanol are thought to be in part mediated by its actions on dopamine neurotransmission, we hypothesized that alcohol-preferring C57BL/6J and alcohol-avoiding DBA/2J mice would display basal differences in dopamine system function. By administering an L-aromatic acid decarboxylase inhibitor and measuring L-Dopa accumulation via high-performance liquid chromatography as a measure of tyrosine hydroxylase activity, we found no difference in dopamine synthesis between mouse strains in the midbrain, dorsal striatum, or ventral striatum. However, we did find that quinpirole-induced inhibition of dopamine synthesis was greater in the ventral striatum of C57BL/6J mice, suggesting increased presynaptic D2-type dopamine autoreceptor sensitivity. To determine whether dopamine synthesis or autoreceptor sensitivity was altered by a history of ethanol, we exposed C57BL/6J mice to one or two weekly cycles of chronic intermittent ethanol (CIE) exposure and withdrawal. We found that there was an attenuation of baseline dopamine synthesis in the ventral striatum after two cycles of CIE. Finally, we examined tissue content of dopamine and dopamine metabolites across recombinant inbred mice bred from a C57BL/6J × DBA/2J cross (BXD). We found that low dopaminergic activity, as indicated by high dopamine/metabolite ratios, was positively correlated with drinking. Together, these findings

  7. Reward system and addiction: what dopamine does and doesn't do.

    Science.gov (United States)

    Di Chiara, Gaetano; Bassareo, Valentina

    2007-02-01

    Addictive drugs share with palatable food the property of increasing extracellular dopamine (DA), preferentially in the nucleus accumbens shell rather than in the core. However, by acting directly on the brain, drugs bypass the adaptive mechanisms (habituation) that constrain the responsiveness of accumbens shell DA to food reward, abnormally facilitating Pavlovian incentive learning and promoting the acquisition of abnormal DA-releasing properties by drug conditioned stimuli. Thus, whereas Pavlovian food conditioned stimuli release core but not shell DA, drug conditioned stimuli do the opposite, releasing shell but not core DA. This process, which results in the acquisition of excessive incentive-motivational properties by drug conditioned stimuli, initiates the drug addiction process. Neuroadaptive processes related to the chronic influence of drugs on subcortical DA might secondarily impair the function of prefronto-striatal loops, resulting in impairments in impulse control and decision making that form the basis for the compulsive feature of drug seeking and its relapsing character.

  8. Role of prefrontal cortex and the midbrain dopamine system in working memory updating

    Science.gov (United States)

    D’Ardenne, Kimberlee; Eshel, Neir; Luka, Joseph; Lenartowicz, Agatha; Nystrom, Leigh E.; Cohen, Jonathan D.

    2012-01-01

    Humans are adept at switching between goal-directed behaviors quickly and effectively. The prefrontal cortex (PFC) is thought to play a critical role by encoding, updating, and maintaining internal representations of task context in working memory. It has also been hypothesized that the encoding of context representations in PFC is regulated by phasic dopamine gating signals. Here we use multimodal methods to test these hypotheses. First we used functional MRI (fMRI) to identify regions of PFC associated with the representation of context in a working memory task. Next we used single-pulse transcranial magnetic stimulation (TMS), guided spatially by our fMRI findings and temporally by previous event-related EEG recordings, to disrupt context encoding while participants performed the same working memory task. We found that TMS pulses to the right dorsolateral PFC (DLPFC) immediately after context presentation, and well in advance of the response, adversely impacted context-dependent relative to context-independent responses. This finding causally implicates right DLPFC function in context encoding. Finally, using the same paradigm, we conducted high-resolution fMRI measurements in brainstem dopaminergic nuclei (ventral tegmental area and substantia nigra) and found phasic responses after presentation of context stimuli relative to other stimuli, consistent with the timing of a gating signal that regulates the encoding of representations in PFC. Furthermore, these responses were positively correlated with behavior, as well as with responses in the same region of right DLPFC targeted in the TMS experiment, lending support to the hypothesis that dopamine phasic signals regulate encoding, and thereby the updating, of context representations in PFC. PMID:23086162

  9. Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

    Science.gov (United States)

    Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

    2018-01-01

    Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Vulnerability analysis of power systems considering uncertainty in variables using fuzzy logic type 2

    Directory of Open Access Journals (Sweden)

    Julian Alexander Melo Rodriguez

    2016-09-01

    Full Text Available Objectives: This paper presents a new methodology for analyzing the vulnerability of power systems including uncertainty in some variables. Method: The methodology optimizes a Bi-level mixed integer model. Costs associated with power generation and load shedding are minimized at the lowest level whereas at the higher level the damage in the power system, represented by the load shedding, is maximized. Fuzzy logic type 2 is used to model the uncertainty in both linguistic variables and numeric variables. The linguistic variables model the factors of the geographical environment while numeric variables model parameters of the power system. Results: The methodology was validated by using a modified IEEE RTS-96 test system. The results show that by including particularities of the geographical environment different vulnerabilities are detected in the power system. Moreover, it was possible to identify that the most critical component is the line 112-123 because it had 16 attacks in 18 scenarios, and that the maximum load shedding of the system varies from 145 to 1258 MW. Conclusions: This methodology can be used to coordinate and refine protection plans of the power system infrastructure. Funding: EMC-UN research group.

  11. A model for assessing the systemic vulnerability in landslide prone areas

    Directory of Open Access Journals (Sweden)

    S. Pascale

    2010-07-01

    Full Text Available The objectives of spatial planning should include the definition and assessment of possible mitigation strategies regarding the effects of natural hazards on the surrounding territory. Unfortunately, however, there is often a lack of adequate tools to provide necessary support to the local bodies responsible for land management. This paper deals with the conception, the development and the validation of an integrated numerical model for assessing systemic vulnerability in complex and urbanized landslide-prone areas. The proposed model considers this vulnerability not as a characteristic of a particular element at risk, but as a peculiarity of a complex territorial system, in which the elements are reciprocally linked in a functional way. It is an index of the tendency of a given territorial element to suffer damage (usually of a functional kind due to its interconnections with other elements of the same territorial system. The innovative nature of this work also lies in the formalization of a procedure based on a network of influences for an adequate assessment of such "systemic" vulnerability.

    This approach can be used to obtain information which is useful, in any given situation of a territory hit by a landslide event, for the identification of the element which has suffered the most functional damage, ie the most "critical" element and the element which has the greatest repercussions on other elements of the system and thus a "decisive" role in the management of the emergency.

    This model was developed within a GIS system through the following phases:

    1. the topological characterization of the territorial system studied and the assessment of the scenarios in terms of spatial landslide hazard. A statistical method, based on neural networks was proposed for the assessment of landslide hazard;

    2. the analysis of the direct consequences of a scenario event on the system;

    3. the definition of the

  12. A Formal Approach to Exploiting Multi-Stage Attacks based on File-System Vulnerabilities of Web Applications (Extended Version)

    OpenAIRE

    De Meo, Federico; Viganò, Luca

    2017-01-01

    Web applications require access to the file-system for many different tasks. When analyzing the security of a web application, secu- rity analysts should thus consider the impact that file-system operations have on the security of the whole application. Moreover, the analysis should take into consideration how file-system vulnerabilities might in- teract with other vulnerabilities leading an attacker to breach into the web application. In this paper, we first propose a classification of file-...

  13. Modeling and Vulnerability Analysis of Cyber-Physical Power Systems Considering Network Topology and Power Flow Properties

    Directory of Open Access Journals (Sweden)

    Jia Guo

    2017-01-01

    Full Text Available Conventional power systems are developing into cyber-physical power systems (CPPS with wide applications of communication, computer and control technologies. However, multiple practical cases show that the failure of cyber layers is a major factor leading to blackouts. Therefore, it is necessary to discuss the cascading failure process considering cyber layer failures and analyze the vulnerability of CPPS. In this paper, a CPPS model, which consists of cyber layer, physical layer and cyber-physical interface, is presented using complex network theory. Considering power flow properties, the impacts of cyber node failures on the cascading failure propagation process are studied. Moreover, two vulnerability indices are established from the perspective of both network structure and power flow properties. A vulnerability analysis method is proposed, and the CPPS performance before and after cascading failures is analyzed by the proposed method to calculate vulnerability indices. In the case study, three typical scenarios are analyzed to illustrate the method, and vulnerabilities under different interface strategies and attack strategies are compared. Two thresholds are proposed to value the CPPS vulnerability roughly. The results show that CPPS is more vulnerable under malicious attacks and cyber nodes with high indices are vulnerable points which should be reinforced.

  14. PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

    Science.gov (United States)

    España, Rodrigo A.; Jones, Sara R.

    2013-01-01

    The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

  15. Exploiting Hardware Vulnerabilities to Attack Embedded System Devices: a Survey of Potent Microarchitectural Attacks

    Directory of Open Access Journals (Sweden)

    Apostolos P. Fournaris

    2017-07-01

    Full Text Available Cyber-Physical system devices nowadays constitute a mixture of Information Technology (IT and Operational Technology (OT systems that are meant to operate harmonically under a security critical framework. As security IT countermeasures are gradually been installed in many embedded system nodes, thus securing them from many well-know cyber attacks there is a lurking danger that is still overlooked. Apart from the software vulnerabilities that typical malicious programs use, there are some very interesting hardware vulnerabilities that can be exploited in order to mount devastating software or hardware attacks (typically undetected by software countermeasures capable of fully compromising any embedded system device. Real-time microarchitecture attacks such as the cache side-channel attacks are such case but also the newly discovered Rowhammer fault injection attack that can be mounted even remotely to gain full access to a device DRAM (Dynamic Random Access Memory. Under the light of the above dangers that are focused on the device hardware structure, in this paper, an overview of this attack field is provided including attacks, threat directives and countermeasures. The goal of this paper is not to exhaustively overview attacks and countermeasures but rather to survey the various, possible, existing attack directions and highlight the security risks that they can pose to security critical embedded systems as well as indicate their strength on compromising the Quality of Service (QoS such systems are designed to provide.

  16. Sex-Dependent Effects of Stress on Immobility Behavior and VTA Dopamine Neuron Activity: Modulation by Ketamine.

    Science.gov (United States)

    Rincón-Cortés, Millie; Grace, Anthony A

    2017-10-01

    Stress constitutes a risk factor across several psychiatric disorders. Moreover, females are more susceptible to stress-related disorders, such as depression, than males. Although dopamine system underactivation is implicated in the pathophysiology of depression, little is known about the female dopamine system at baseline and post-stress. The effects of chronic mild stress were examined on ventral tegmental area dopamine neuron activity and forced swim test immobility by comparing male and female rats. The impact of a single dose of the rapid antidepressant ketamine (10 mg/kg, i.p.) on forced swim test immobility and ventral tegmental area function was then tested. Baseline ventral tegmental area dopamine activity was comparable in both sexes. At baseline, females exhibited roughly double the forced swim test immobility duration than males, which corresponded to ~50% decrease in ventral tegmental area dopamine population activity compared with similarly treated (i.e., post-forced swim test) males. Following chronic mild stress, there was greater immobility duration in both sexes and reduced ventral tegmental area dopamine neuron activity by approximately 50% in males and nearly 75% in females. Ketamine restored behavior and post-forced swim test ventral tegmental area dopamine activity for up to 7 days in females as well as in both male and female chronic mild stress-exposed rats. These data suggest increased female susceptibility to depression-like phenotypes (i.e., greater immobility, ventral tegmental area hypofunction) is associated with higher dopamine system sensitivity to both acute and repeated stress relative to males. Understanding the neural underpinnings of sex differences in stress vulnerability will provide insight into mechanisms of disease and optimizing therapeutic approaches in both sexes. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  17. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

    Directory of Open Access Journals (Sweden)

    James P. Kesby

    2013-07-01

    Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  18. Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory.

    Science.gov (United States)

    Ikemoto, Satoshi

    2010-11-01

    Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward emerge out of neuronal activity. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures-the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In addition, studies found roles of non-dopaminergic mechanisms of the supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward. To explain intracranial self-administration and related effects of various drug manipulations, I outlined a neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach. Further, this coordinating process for approach arises from interactions between brain structures including those structures mentioned above and their closely linked regions: the medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus and parabrachical area. Published by Elsevier Ltd.

  19. The influence of leptin on the dopamine system and implications for ingestive behavior.

    Science.gov (United States)

    DiLeone, R J

    2009-06-01

    Food intake is regulated by many factors, including sensory information, metabolic hormones and the state of hunger. In modern humans, the drive to eat has proven to be incompatible with the excess food supply present in industrialized societies. A result of this imbalance is the dramatically increased rates of obesity during the last 20 years. The rise in obesity rates poses one of the most significant public health issues facing the United States and yet we do not understand the neural basis of ingestive behavior, and specifically, our motivation to eat. Understanding how the brain controls eating will lay the foundation for systematic dissection, understanding and treatment of obesity and related disorders. The lack of control over food intake bears resemblance to drug addiction, where loss of control over behavior leads to compulsive drug use. Work in laboratory animals has long suggested that there exist common neural substrates underlying both food and drug intake behaviors. Recent studies have shown direct leptin effects on dopamine neuron function and behavior. This provides a new mechanism by which peripheral hormones influence behavior and contribute to a more comprehensive model of neural control over food intake.

  20. Impact, adaptation and vulnerability of natural and human systems in Europe

    International Nuclear Information System (INIS)

    Martin, Eric; Salas y Melia, David; Delire, Christine; Lemonsu, Aude; Masson, Valery; Badeau, Vincent; Gattuso, Jean-Pierre; Pigeon, Gregoire; Regimbeau, Mathieu; Viguie, Vincent

    2015-01-01

    This article analyses the observed and projected impacts of climate change on human and natural systems, their vulnerability and adaptation options. It provides insight into the main results related to hydrology, agriculture, natural ecosystems, transport, energy, tourism, infrastructures, health and social aspects. This article presents the main results concerning Europe that were compiled in the contribution of Working Group II to the IPCC fifth assessment report published in 2014. Several studies focused on mainland France are also presented, without claiming to be exhaustive. (authors)

  1. Nature of rate-limiting steps in a compartmentalized enzyme system. Quantitation of dopamine transport and hydroxylation rates in resealed chromaffin granule ghosts

    International Nuclear Information System (INIS)

    Ahn, N.G.; Klinman, J.P.

    1989-01-01

    Using isolated chromaffin granule ghosts from bovine adrenal medullae, we have studied the kinetics of dopamine beta-monooxygenase (D beta M) activity as it is linked to dopamine transport. Measurements of the initial rates of transport and of transport-linked norepinephrine formation suggested that enzyme activity may be partially rate-limiting in the coupled carrier/enzyme system. This was confirmed by (i) measurements of initial rates of norepinephrine formation using deuterated substrate, which gave isotope effects greater than 2.0, and (ii) kinetic measurements using ghosts pulsed with varying concentrations of labeled dopamine, which indicated substantial substrate accumulation in the vesicle interior as a function of time. Initial rates of product formation, when combined with approximations of internal substrate concentrations, allowed estimates of Kcat and Km for intravesicular D beta M. Activation by external reductant was apparent in both initial rate parameters and the measurements of transients. Under conditions of optimal D beta M activity, the enzyme rate parameters (kcat = 0.31 nmol/s.mg and Km = 2 mM) indicated partial rate limitation compared to dopamine transport (kcat = 0.38 nmol/s.mg and Km = 32 microM). Compartmental analysis of the time curves, performed using numerical nonlinear least squares methods, gave least squares estimates of rate constants for a simple carrier mechanism and kcat values for D beta M which were consistent with estimates from initial rates

  2. Assessing the Vulnerability of Public-Supply Wells to Contamination: Floridan Aquifer System Near Tampa, Florida

    Science.gov (United States)

    Jagucki, Martha L.; Katz, Brian G.; Crandall, Christy A.; Eberts, Sandra M.

    2009-01-01

    This fact sheet highlights findings from the vulnerability study of a public-supply well in Temple Terrace, Florida, northeast of Tampa. The well selected for study typically produces water at the rate of 700 gallons per minute from the Upper Floridan aquifer. Water samples were collected at the public-supply well and at monitoring wells installed in or near the simulated zone of contribution to the supply well. Samples of untreated water from the public-supply wellhead contained the undesirable constituents nitrate, arsenic, uranium, radon-222, volatile organic compounds (VOCs), and pesticides, although all were detected at concentrations less than established drinking-water standards, where such standards exist. Overall, study findings point to four primary factors that affect the movement and fate of contaminants and the vulnerability of the public-supply well in Temple Terrace: (1) groundwater age (how long ago water entered, or recharged, the aquifer); (2) short-circuiting of contaminated water through sinkholes; (3) natural geochemical processes within the aquifer; and (4) pumping stress. Although the public-supply well is completed in the Upper Floridan aquifer, it produces water with concentrations of nitrate, VOCs, and the natural contaminant radon that are intermediate between the typical composition of water from the Upper Floridan aquifer and that of the overlying surficial aquifer system. Mixing calculations show that the water produced by the public-supply well could consist of upwards of 50 percent water from the surficial aquifer system mixed with water from the Upper Floridan aquifer. Anthropogenically affected water from the surficial aquifer system travels rapidly to depth through sinkholes that must be directly connected to the cavernous zone intersected by the public-supply well (and several other production wells in the region). Such solution features serve as fast pathways to the well and circumvent the natural attenuation of nitrate and

  3. Transportation System Vulnerability and Resilience to Extreme Weather Events and Other Natural Hazards : Final Results of Vulnerability Assessment of National Highway System for All KYTC Districts

    Science.gov (United States)

    2018-05-01

    Recent federal legislation and the Federal Highway Administration (FHWA) have directed state transportation agencies to identify potential vulnerabilities associated with extreme weather events and climate change, develop a risk-based asset managemen...

  4. Using a Coupled Human-Natural System to Assess the Vulnerability of the Karst Landform Region in China

    Directory of Open Access Journals (Sweden)

    Xiang He

    2015-09-01

    Full Text Available Guizhou Plateau is a region in China that typically shows the contradictory human-earth system. A vulnerability assessment indicator system was constructed to explore the coupled human-natural system characteristic of the karst landform based on the grey correlation analysis mathematic model. The quantitative assessment results show that Qiandongnan and Tongren Districts belong to the slight degree of the sensitivity evaluation index. Bijie district belongs to the middle degree and the other districts of Guizhou Plateau belong to the light degree. In terms of the exposure and resilience evaluation index, only Guiyang City belongs to the slight degree and other districts are in the middle degree. Thus, Guizhou Plateau could be divided into three level zones based on the comprehensive vulnerability degree of the coupled human-natural system. The strong degree vulnerability zone includes Liupanshui City, Bijie City, Anshun City, and Qiannan District. The middle degree vulnerability zone includes the districts of Qiandongnan, Qianxinan, and Tongren and the city of Zunyi. The slight degree vulnerability zone only includes Guiyang City. The research results suggest that the coupled human-natural system in Guizhou Plateau has a high vulnerability.

  5. Cyber Security for the Spaceport Command and Control System: Vulnerability Management and Compliance Analysis

    Science.gov (United States)

    Gunawan, Ryan A.

    2016-01-01

    With the rapid development of the Internet, the number of malicious threats to organizations is continually increasing. In June of 2015, the United States Office of Personnel Management (OPM) had a data breach resulting in the compromise of millions of government employee records. The National Aeronautics and Space Administration (NASA) is not exempt from these attacks. Cyber security is becoming a critical facet to the discussion of moving forward with projects. The Spaceport Command and Control System (SCCS) project at the Kennedy Space Center (KSC) aims to develop the launch control system for the next generation launch vehicle in the coming decades. There are many ways to increase the security of the network it uses, from vulnerability management to ensuring operating system images are compliant with securely configured baselines recommended by the United States Government.

  6. Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response.

    Science.gov (United States)

    Zervantonakis, Ioannis K; Iavarone, Claudia; Chen, Hsing-Yu; Selfors, Laura M; Palakurthi, Sangeetha; Liu, Joyce F; Drapkin, Ronny; Matulonis, Ursula; Leverson, Joel D; Sampath, Deepak; Mills, Gordon B; Brugge, Joan S

    2017-08-28

    The lack of effective chemotherapies for high-grade serous ovarian cancers (HGS-OvCa) has motivated a search for alternative treatment strategies. Here, we present an unbiased systems-approach to interrogate a panel of 14 well-annotated HGS-OvCa patient-derived xenografts for sensitivity to PI3K and PI3K/mTOR inhibitors and uncover cell death vulnerabilities. Proteomic analysis reveals that PI3K/mTOR inhibition in HGS-OvCa patient-derived xenografts induces both pro-apoptotic and anti-apoptotic signaling responses that limit cell killing, but also primes cells for inhibitors of anti-apoptotic proteins. In-depth quantitative analysis of BCL-2 family proteins and other apoptotic regulators, together with computational modeling and selective anti-apoptotic protein inhibitors, uncovers new mechanistic details about apoptotic regulators that are predictive of drug sensitivity (BIM, caspase-3, BCL-X L ) and resistance (MCL-1, XIAP). Our systems-approach presents a strategy for systematic analysis of the mechanisms that limit effective tumor cell killing and the identification of apoptotic vulnerabilities to overcome drug resistance in ovarian and other cancers.High-grade serous ovarian cancers (HGS-OvCa) frequently develop chemotherapy resistance. Here, the authors through a systematic analysis of proteomic and drug response data of 14 HGS-OvCa PDXs demonstrate that targeting apoptosis regulators can improve response of these tumors to inhibitors of the PI3K/mTOR pathway.

  7. NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-08-01

    Full Text Available Dopamine is one of the principal neurotransmitters in the central nervous system (CNC, and its neuronal pathways are involved in several key functions such as behavior (Hefco et al., 2003a,b, control of movement, endocrine regulation, immune response (Fiserova et al., 2002; Levite et al., 2001, Hritcu et al., 2006a,b,c, and cardiovascular function. Dopamine has at least five G-protein, coupled receptor subtypes, D1-D5, each arising from a different gene (Sibley et al., 1993. Traditionally, these receptors have been classified into D1-like (the D1 and D5 and D2-like (D2, D3 and D4 receptors subtypes, primarily according to their ability to stimulate or inhibit adenylate cyclase, respectively, and to their pharmacological characteristics (Seeman et al., 1993. Receptors for dopamine (particularly of D2 subclass are the primary therapeutic target in a number of neuropathological disorders including schizophrenia, Parkinson’s disease and Huntington’s chorea (Seeman et al., 1987. Neither dopamine by itself, nor dopaminergic agonists by themselves, has been shown to activate T cell function. Nevertheless, lymphocytes are most probably exposed to dopamine since the primary and secondary lymphoid organs of various mammals are markedly innervated, and contain nerve fibers which stain for tyrosine hydroxylase (Weihe et al., 1991, the enzyme responsible for dopamine synthesis. Moreover, cathecolamines and their metabolites are present in single lymphocytes and in extracts of T and B cell clones, and pharmacological inhibition of tyrosine hydroxylase reduces catecholamine levels, suggesting catecholamine synthesis by lymphocytes (Bergquist et al., 1994. The existence of putative dopamine receptors of D2, D3, D4 and D5 subtypes on immune cells has been proposed of several authors, primarily on the basis of dopaminergic ligand binding assays and specific mRNA expression as monitored by reverse transcription-PCR. Several experiments evoked the idea of a

  8. Tsunami vulnerability assessment mapping for the west coast of Peninsular Malaysia using a geographical information system (GIS)

    International Nuclear Information System (INIS)

    Najihah, R; Effendi, D M; Hairunnisa, M A; Masiri, K

    2014-01-01

    The catastrophic Indian Ocean tsunami of 26 December 2004 raised a number of questions for scientist and politicians on how to deal with the tsunami risk and assessment in coastal regions. This paper discusses the challenges in tsunami vulnerability assessment and presents the result of tsunami disaster mapping and vulnerability assessment study for West Coast of Peninsular Malaysia. The spatial analysis was carried out using Geographical Information System (GIS) technology to demarcate spatially the tsunami affected village's boundary and suitable disaster management program can be quickly and easily developed. In combination with other thematic maps such as road maps, rail maps, school maps, and topographic map sheets it was possible to plan the accessibility and shelter to the affected people. The tsunami vulnerability map was used to identify the vulnerability of villages/village population to tsunami. In the tsunami vulnerability map, the intensity of the tsunami was classified as hazard zones based on the inundation level in meter (contour). The approach produced a tsunami vulnerability assessment map consists of considering scenarios of plausible extreme, tsunami-generating events, computing the tsunami inundation levels caused by different events and scenarios and estimating the possible range of casualties for computing inundation levels. The study provides an interactive means to identify the tsunami affected areas after the disaster and mapping the tsunami vulnerable village before for planning purpose were the essential exercises for managing future disasters

  9. Tsunami vulnerability assessment mapping for the west coast of Peninsular Malaysia using a geographical information system (GIS)

    Science.gov (United States)

    Najihah, R.; Effendi, D. M.; Hairunnisa, M. A.; Masiri, K.

    2014-02-01

    The catastrophic Indian Ocean tsunami of 26 December 2004 raised a number of questions for scientist and politicians on how to deal with the tsunami risk and assessment in coastal regions. This paper discusses the challenges in tsunami vulnerability assessment and presents the result of tsunami disaster mapping and vulnerability assessment study for West Coast of Peninsular Malaysia. The spatial analysis was carried out using Geographical Information System (GIS) technology to demarcate spatially the tsunami affected village's boundary and suitable disaster management program can be quickly and easily developed. In combination with other thematic maps such as road maps, rail maps, school maps, and topographic map sheets it was possible to plan the accessibility and shelter to the affected people. The tsunami vulnerability map was used to identify the vulnerability of villages/village population to tsunami. In the tsunami vulnerability map, the intensity of the tsunami was classified as hazard zones based on the inundation level in meter (contour). The approach produced a tsunami vulnerability assessment map consists of considering scenarios of plausible extreme, tsunami-generating events, computing the tsunami inundation levels caused by different events and scenarios and estimating the possible range of casualties for computing inundation levels. The study provides an interactive means to identify the tsunami affected areas after the disaster and mapping the tsunami vulnerable village before for planning purpose were the essential exercises for managing future disasters.

  10. Vulnerability Identification and Design-Improvement-Feedback using Failure Analysis of Digital Control System Designs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunchan; Bae, Yeonkyoung [Korea Hydro and Nuclear Power Co., Ltd., Daejeon (Korea, Republic of)

    2013-05-15

    Fault tree analyses let analysts establish the failure sequences of components as a logical model and confirm the result at the plant level. These two analyses provide insights regarding what improvements are needed to increase availability because it expresses the quantified design attribute of the system as minimal cut sets and availability value interfaced with component reliability data in the fault trees. This combined failure analysis method helps system users understand system characteristics including its weakness and strength in relation to faults in the design stage before system operation. This study explained why a digital system could have weaknesses in methods to transfer control signals or data and how those vulnerabilities could cause unexpected outputs. In particular, the result of the analysis confirmed that complex optical communication was not recommended for digital data transmission in the critical systems of nuclear power plants. Regarding loop controllers in Design A, a logic configuration should be changed to prevent spurious actuation due to a single failure, using hardware or software improvements such as cross checking between redundant modules, or diagnosis of the output signal integrity. Unavailability calculations support these insights from the failure analyses of the systems. In the near future, KHNP will perform failure mode and effect analyses in the design stage before purchasing non-safety-related digital system packages. In addition, the design requirements of the system will be confirmed based on evaluation of overall system availability or unavailability.

  11. Using wavefront coding technique as an optical encryption system: reliability analysis and vulnerabilities assessment

    Science.gov (United States)

    Konnik, Mikhail V.

    2012-04-01

    Wavefront coding paradigm can be used not only for compensation of aberrations and depth-of-field improvement but also for an optical encryption. An optical convolution of the image with the PSF occurs when a diffractive optical element (DOE) with a known point spread function (PSF) is placed in the optical path. In this case, an optically encoded image is registered instead of the true image. Decoding of the registered image can be performed using standard digital deconvolution methods. In such class of optical-digital systems, the PSF of the DOE is used as an encryption key. Therefore, a reliability and cryptographic resistance of such an encryption method depends on the size and complexity of the PSF used for optical encoding. This paper gives a preliminary analysis on reliability and possible vulnerabilities of such an encryption method. Experimental results on brute-force attack on the optically encrypted images are presented. Reliability estimation of optical coding based on wavefront coding paradigm is evaluated. An analysis of possible vulnerabilities is provided.

  12. Focusing Conservation Efforts on Ecosystem Service Supply May Increase Vulnerability of Socio-Ecological Systems.

    Directory of Open Access Journals (Sweden)

    Pedro Laterra

    Full Text Available Growing concern about the loss of ecosystem services (ES promotes their spatial representation as a key tool for the internalization of the ES framework into land use policies. Paradoxically, mapping approaches meant to inform policy decisions focus on the magnitude and spatial distribution of the biophysical supply of ES, largely ignoring the social mechanisms by which these services influence human wellbeing. If social mechanisms affecting ES demand, enhancing it or reducing it, are taken more into account, then policies are more effective. By developing and applying a new mapping routine to two distinct socio-ecological systems, we show a strong spatial uncoupling between ES supply and socio-ecological vulnerability to the loss of ES, under scenarios of land use and cover change. Public policies based on ES supply might not only fail at detecting priority conservation areas for the wellbeing of human societies, but may also increase their vulnerability by neglecting areas of currently low, but highly valued ES supply.

  13. Analyzing Risks and Vulnerabilities of Various Computer Systems and Undergoing Exploitation using Embedded Devices

    Science.gov (United States)

    Branch, Drew Alexander

    2014-01-01

    Security is one of the most if not the most important areas today. After the several attacks on the United States, security everywhere has heightened from airports to communication among the military branches legionnaires. With advanced persistent threats (APTs) on the rise following Stuxnet, government branches and agencies are required, more than ever, to follow several standards, policies and procedures to reduce the likelihood of a breach. Attack vectors today are very advanced and are going to continue to get more and more advanced as security controls advance. This creates a need for networks and systems to be in an updated, patched and secured state in a launch control system environment. Attacks on critical systems are becoming more and more relevant and frequent. Nation states are hacking into critical networks that might control electrical power grids or water dams as well as carrying out advanced persistent threat (APTs) attacks on government entities. NASA, as an organization, must protect its self from attacks from all different types of attackers with different motives. Although the International Space Station was created, there is still competition between the different space programs. With that in mind, NASA might get attacked and breached for various reasons such as espionage or sabotage. My project will provide a way for NASA to complete an in house penetration test which includes: asset discovery, vulnerability scans, exploit vulnerabilities and also provide forensic information to harden systems. Completing penetration testing is a part of the compliance requirements of the Federal Information Security Act (FISMA) and NASA NPR 2810.1 and related NASA Handbooks. This project is to demonstrate how in house penetration testing can be conducted that will satisfy all of the compliance requirements of the National Institute of Standards and Technology (NIST), as outlined in FISMA. By the end of this project, I hope to have carried out the tasks stated

  14. A novel G protein-coupled receptor of Schistosoma mansoni (SmGPR-3 is activated by dopamine and is widely expressed in the nervous system.

    Directory of Open Access Journals (Sweden)

    Fouad El-Shehabi

    Full Text Available Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention. Neurotransmitter receptors, in particular those involved in neuromuscular control, are proven drug targets in other helminths but very few of these receptors have been identified in schistosomes and little is known about their roles in the biology of the worm. Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named SmGPR-3 that was cloned, expressed heterologously and shown to be activated by dopamine, a well established neurotransmitter of the schistosome nervous system. SmGPR-3 belongs to a new clade of "orphan" amine-like receptors that exist in schistosomes but not the mammalian host. Further analysis of the recombinant protein showed that SmGPR-3 can also be activated by other catecholamines, including the dopamine metabolite, epinine, and it has an unusual antagonist profile when compared to mammalian receptors. Confocal immunofluorescence experiments using a specific peptide antibody showed that SmGPR-3 is abundantly expressed in the nervous system of schistosomes, particularly in the main nerve cords and the peripheral innervation of the body wall muscles. In addition, we show that dopamine, epinine and other dopaminergic agents have strong effects on the motility of larval schistosomes in culture. Together, the results suggest that SmGPR-3 is an important neuronal receptor and is probably involved in the control of motor activity in schistosomes. We have conducted a first analysis of the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking simulations. This investigation has identified potentially important differences between SmGPR-3 and host dopamine receptors that could be exploited to develop new, parasite-selective anti-schistosomal drugs.

  15. Seismic Failure Mechanism of Reinforced Cold-Formed Steel Shear Wall System Based on Structural Vulnerability Analysis

    Directory of Open Access Journals (Sweden)

    Jihong Ye

    2017-02-01

    Full Text Available A series of structural vulnerability analyses are conducted on a reinforced cold-formed steel (RCFS shear wall system and a traditional cold-formed steel (CFS shear wall system subjected to earthquake hazard based on forms in order to investigate their failure mechanisms. The RCFS shear wall adopts rigid beam-column joints and continuous concrete-filled CFS tube end studs rather than coupled-C section end studs that are used in traditional CFS shear walls, to achieve the rigid connections in both beam-column joints and column bases. The results show that: the RCFS and traditional CFS shear wall systems both exhibit the maximum vulnerability index associated with the failure mode in the first story. Therefore, the first story is likely to be a weakness of the CFS shear wall system. Once the wall is damaged, the traditional CFS shear wall system would collapse because the shear wall is the only lateral-resisting component. However, the collapse resistance of the RCFS shear wall system is effectively enhanced by the second defense, which is provided by a framework integrated by rigid beam-column joints and fixed column bases. The predicted collapse mode with maximum vulnerability index that was obtained by structural vulnerability analysis agrees well with the experimental result, and the structural vulnerability method is thereby verified to be reasonable to identify the weaknesses of framed structures and predict their collapse modes. Additionally, the quantitative vulnerability index indicates that the RCFS shear wall system exhibits better robustness compared to the traditional one. Furthermore, the “strong frame weak wallboard” and the “strong column weak beam” are proposed in this study as conceptional designations for the RCFS shear wall systems.

  16. Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome.

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

    Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS\\/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b\\/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4\\/352.4 vs. 76.7\\/139.4, P < 0.001) as were endothelial E-selectin\\/ICAM-1 expression compared with normal EC (8.1\\/9 vs. 3.9\\/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b\\/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN\\/EC that were not treated dopamine (174\\/240 vs. 252\\/352, P < 0.05 and 4\\/4.4 vs. 8.1\\/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium

  17. Assessment of Coastal Vulnerability to Sea Level Rise of Bolinao, Pangasinan Using Remote Sensing and Geographic Information Systems

    Science.gov (United States)

    Reyes, S. R. C.; Blanco, A. C.

    2012-07-01

    A number of studies assessing the vulnerability of Southeast Asia to climate change have classified the Philippines as one of the vulnerable countries in the region. Bolinao, Pangasinan is a municipality located in northwestern Luzon, situated in the western part of the Lingayen Gulf and is bounded on the north and west by the South China Sea (West Philippine Sea). Recent studies have verified the varying trends in sea level across the South China Sea, which is considered as one of the largest, semi-enclosed marginal seas in the northwest Pacific Ocean. Three barangays (villages) were included in the study: (1) Luciente 1.0, (2) Concordia and (3) Germinal. The Socioeconomic Vulnerability Index (SVI) was computed based on population, age, gender, employment, source of income and household size, which were gathered through a qualitative survey in the selected barangays. The Coastal Vulnerability Index (CVI) described the physical vulnerability of these coastal communities based on recorded sea level anomalies and significant wave heights of multiple satellite altimetry missions, coastal topography derived from the 25-m SRTM digital elevation model (DEM), bathymetry from WorldView-2 and additional elevation data from terrestrial laser scanning surveys. The research utilized merged satellite altimetry data downloaded from the Radar Altimetry Database System (RADS), which covered the period from 1991-2010. The SVI and CVI were calculated and evaluated in ArcGIS. The SVI and CVI were integrated to determine the Total Vulnerability Index (TVI), which characterized the vulnerability of the three barangays in five classes, from very low to very high vulnerability.

  18. ASSESSMENT OF COASTAL VULNERABILITY TO SEA LEVEL RISE OF BOLINAO, PANGASINAN USING REMOTE SENSING AND GEOGRAPHIC INFORMATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    S. R. C. Reyes

    2012-07-01

    Full Text Available A number of studies assessing the vulnerability of Southeast Asia to climate change have classified the Philippines as one of the vulnerable countries in the region. Bolinao, Pangasinan is a municipality located in northwestern Luzon, situated in the western part of the Lingayen Gulf and is bounded on the north and west by the South China Sea (West Philippine Sea. Recent studies have verified the varying trends in sea level across the South China Sea, which is considered as one of the largest, semi-enclosed marginal seas in the northwest Pacific Ocean. Three barangays (villages were included in the study: (1 Luciente 1.0, (2 Concordia and (3 Germinal. The Socioeconomic Vulnerability Index (SVI was computed based on population, age, gender, employment, source of income and household size, which were gathered through a qualitative survey in the selected barangays. The Coastal Vulnerability Index (CVI described the physical vulnerability of these coastal communities based on recorded sea level anomalies and significant wave heights of multiple satellite altimetry missions, coastal topography derived from the 25-m SRTM digital elevation model (DEM, bathymetry from WorldView-2 and additional elevation data from terrestrial laser scanning surveys. The research utilized merged satellite altimetry data downloaded from the Radar Altimetry Database System (RADS, which covered the period from 1991–2010. The SVI and CVI were calculated and evaluated in ArcGIS. The SVI and CVI were integrated to determine the Total Vulnerability Index (TVI, which characterized the vulnerability of the three barangays in five classes, from very low to very high vulnerability.

  19. Collision and displacement vulnerability among marine birds of the California Current System associated with offshore wind energy infrastructure

    Science.gov (United States)

    Adams, Josh; Kelsey, Emily C.; Felis, Jonathan J.; Pereksta, David M.

    2016-10-27

    With growing climate change concerns and energy constraints, there is an increasing need for renewable energy sources within the United States and globally. Looking forward, offshore wind-energy infrastructure (OWEI) has the potential to produce a significant proportion of the power needed to reach our Nation’s renewable energy goal. Offshore wind-energy sites can capitalize open areas within Federal waters that have persistent, high winds with large energy production potential. Although there are few locations in the California Current System (CCS) where it would be acceptable to build pile-mounted wind turbines in waters less than 50 m deep, the development of technology able to support deep-water OWEI (>200 m depth) could enable wind-energy production in the CCS. As with all human-use of the marine environment, understanding the potential impacts of wind-energy infrastructure on the marine ecosystem is an integral part of offshore wind-energy research and planning. Herein, we present a comprehensive database to quantify marine bird vulnerability to potential OWEI in the CCS (see https://doi.org/10.5066/F79C6VJ0). These data were used to quantify marine bird vulnerabilities at the population level. For 81 marine bird species present in the CCS, we created three vulnerability indices: Population Vulnerability, Collision Vulnerability, and Displacement Vulnerability. Population Vulnerability was used as a scaling factor to generate two comprehensive indicies: Population Collision Vulnerability (PCV) and Population Displacement Vulnerability (PDV). Within the CCS, pelicans, terns (Forster’s [Sterna forsteri], Caspian [Hydroprogne caspia], Elegant [Thalasseus elegans], and Least Tern [Sternula antillarum]), gulls (Western [Larus occidentalis] and Bonaparte’s Gull [Chroicocephalus philadelphia]), South Polar Skua (Stercorarius maccormicki), and Brandt’s Cormorant (Phalacrocorax penicillatus) had the greatest PCV scores. Brown Pelican (Pelicanus occidentalis

  20. Web-Enabling an Early Warning and Tracking System for Network Vulnerabilities

    National Research Council Canada - National Science Library

    Coffman, James

    2001-01-01

    .... Additionally, it lacked support for automated data validation, resulting in unreliable vulnerability tracking information As a result, the process was ineffective, and Navy networks remained highly...

  1. Vulnerability And Risk Assessment Using The Homeland-Defense Operational Planning System (HOPS)

    International Nuclear Information System (INIS)

    Durling, R.L. Jr.; Price, D.E.; Spero, K.K.

    2005-01-01

    For over ten years, the Counterproliferation Analysis and Planning System (CAPS) at Lawrence Livermore National Laboratory (LLNL) has been a planning tool used by U.S. combatant commands for mission support planning against foreign programs engaged in the manufacture of weapons of mass destruction (WMD). CAPS is endorsed by the Secretary of Defense as the preferred counterproliferation tool to be used by the nation's armed services. A sister system, the Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging CAPS expertise designed to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors, HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities is presented

  2. Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

    Science.gov (United States)

    Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

    2017-09-01

    CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal

  3. Vulnerability of Rehabilitated Agricultural Production Systems to Invasion by Nontarget Plant Species

    Science.gov (United States)

    Baer, Sara G.; Engle, David M.; Knops, Johannes M. H.; Langeland, Kenneth A.; Maxwell, Bruce D.; Menalled, Fabian D.; Symstad, Amy J.

    2009-02-01

    Vast areas of arable land have been retired from crop production and “rehabilitated” to improved system states through landowner incentive programs in the United States (e.g., Conservation and Wetland Reserve Programs), as well as Europe (i.e., Agri-Environment Schemes). Our review of studies conducted on invasion of rehabilitated agricultural production systems by nontarget species elucidates several factors that may increase the vulnerability of these systems to invasion. These systems often exist in highly fragmented and agriculturally dominated landscapes, where propagule sources of target species for colonization may be limited, and are established under conditions where legacies of past disturbance persist and prevent target species from persisting. Furthermore, rehabilitation approaches often do not include or successfully attain all target species or historical ecological processes (e.g., hydrology, grazing, and/or fire cycles) key to resisting invasion. Uncertainty surrounds ways in which nontarget species may compromise long term goals of improving biodiversity and ecosystem services through rehabilitation efforts on former agricultural production lands. This review demonstrates that more studies are needed on the extent and ecological impacts of nontarget species as related to the goals of rehabilitation efforts to secure current and future environmental benefits arising from this widespread conservation practice.

  4. The vulnerability of the European agriculture and food system for calamities and geopolitics : a stress test

    NARCIS (Netherlands)

    Weijden, van der W.; Burger, C.P.J.; Jansen, D.M.; Rougoor, C.; Hees, E.

    2011-01-01

    During the 1960s and 1970s, the EU succeeded in becoming largely self-sufficient in food production, thus assuring its food security for the most part. However, it is unclear which areas of food security are still vulnerable and/or whether there are there new vulnerabilities. In this report we have

  5. Effect of U and 137Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat

    International Nuclear Information System (INIS)

    Houpert, P.; Lestaevel, P.; Amourette, C.; Dhieux, B.; Bussy, C.; Paquet, F.

    2004-01-01

    Following the Chernobyl accident, the most significant problem for the population of the former Soviet Union for the next 50-70 years will be chronic internal contamination by radionuclides. One of the few experiments carried out in this field reported that neurotransmitter metabolism in the central nervous system of the rat was disturbed after feeding with oats contaminated by 137 Cs for 1 month. The present study assessed the effect of chronic contamination by depleted U or 137 Cs on the metabolism of two neurotransmitters in cerebral areas of rats. Dopamine and serotonin were chosen because their metabolism has been shown to be disturbed after external irradiation, even at moderate doses. Dopamine, serotonin, and some of their catabolites were measured by high-pressure liquid chromatography coupled with an electrochemical detector in five cerebral structures of rats contaminated over a 1-month period by drinking water (40 mg U·L -1 or 6500 Bq 137 Cs·L -1 ). In the striatum, hippocampus, cerebral cortex, thalamus, and cerebellum, the dopamine, serotonin, and catabolite levels were not significantly different between the control rats and rats contaminated by U or 137 Cs. These results are not in accordance with those previously described. (author)

  6. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network

    Directory of Open Access Journals (Sweden)

    Avijit Podder

    2017-06-01

    Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  7. Automated Software Vulnerability Analysis

    Science.gov (United States)

    Sezer, Emre C.; Kil, Chongkyung; Ning, Peng

    Despite decades of research, software continues to have vulnerabilities. Successful exploitations of these vulnerabilities by attackers cost millions of dollars to businesses and individuals. Unfortunately, most effective defensive measures, such as patching and intrusion prevention systems, require an intimate knowledge of the vulnerabilities. Many systems for detecting attacks have been proposed. However, the analysis of the exploited vulnerabilities is left to security experts and programmers. Both the human effortinvolved and the slow analysis process are unfavorable for timely defensive measure to be deployed. The problem is exacerbated by zero-day attacks.

  8. Requirements of a system to reduce car-to-vulnerable road user crashes in urban intersections.

    Science.gov (United States)

    Habibovic, Azra; Davidsson, Johan

    2011-07-01

    Intersection crashes between cars and vulnerable road users (VRUs), such as pedestrians and bicyclists, often result in injuries and fatalities. Advanced driver assistance systems (ADASs) can prevent, or mitigate, these crashes. To derive functional requirements for such systems, an understanding of the underlying contributing factors and the context in which the crashes occur is essential. The aim of this study is to use microscopic and macroscopic crash data to explore the potential of information and warning providing ADASs, and then to derive functional sensor, collision detection, and human-machine interface (HMI) requirements. The microscopic data were obtained from the European project SafetyNet. Causation charts describing contributing factors for 60 car-to-VRU crashes had been compiled and were then also aggregated using the SafetyNet Accident Causation System (SNACS). The macroscopic data were obtained from the Swedish national crash database, STRADA. A total of 9702 crashes were analyzed. The results show that the most frequent contributing factor to the crashes was the drivers' failure to observe VRUs due to reduced visibility, reduced awareness, and/or insufficient comprehension. An ADAS should therefore help drivers to observe the VRUs in time and to enhance their ability to interpret the development of events in the near future. The system should include a combination of imminent and cautionary collision warnings, with additional support in the form of information about intersection geometry and traffic regulations. The warnings should be deployed via an in-vehicle HMI and according to the likelihood of crash risk. The system should be able to operate under a variety of weather and light conditions. It should have the capacity to support drivers when their view is obstructed by physical objects. To address problems that vehicle-based sensors may face in this regard, the use of cooperative systems is recommended. Copyright © 2011 Elsevier Ltd. All

  9. Protective effects of the thioredoxin and glutaredoxin systems in dopamine-induced cell death

    OpenAIRE

    Arodin, Lisa; Miranda-Vizuete, Antonio; Swoboda, Peter; Fernandes, Aristi P.

    2014-01-01

    Although the etiology of sporadic Parkinson disease (PD) is unknown, it is well established that oxidative stress plays an important role in the pathogenic mechanism. The thioredoxin (Trx) and glutaredoxin (Grx) systems are two central systems upholding the sulfhydryl homeostasis by reducing disulfides and mixed disulfides within the cell and thereby protecting against oxidative stress. By examining the expression of redox proteins in human postmortem PD brains, we found the levels of Trx1 an...

  10. NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.

    Science.gov (United States)

    Tan, Huibing; Rosen, Laura G; Ng, Garye A; Rushlow, Walter J; Laviolette, Steven R

    2014-12-01

    N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood. This study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA). Using an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings. We show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism. These findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

  11. GIS Fuzzy Expert System for the assessment of ecosystems vulnerability to fire in managing Mediterranean natural protected areas.

    Science.gov (United States)

    Semeraro, Teodoro; Mastroleo, Giovanni; Aretano, Roberta; Facchinetti, Gisella; Zurlini, Giovanni; Petrosillo, Irene

    2016-03-01

    A significant threat to the natural and cultural heritage of Mediterranean natural protected areas (NPAs) is related to uncontrolled fires that can cause potential damages related to the loss or a reduction of ecosystems. The assessment and mapping of the vulnerability to fire can be useful to reduce landscape damages and to establish priority areas where it is necessary to plan measures to reduce the fire vulnerability. To this aim, a methodology based on an interactive computer-based system has been proposed in order to support NPA's management authority for the identification of vulnerable hotspots to fire through the selection of suitable indicators that allow discriminating different levels of sensitivity (e.g. Habitat relevance, Fragmentation, Fire behavior, Ecosystem Services, Vegetation recovery after fire) and stresses (agriculture, tourism, urbanization). In particular, a multi-criteria analysis based on Fuzzy Expert System (FES) integrated in a GIS environment has been developed in order to identify and map potential "hotspots" of fire vulnerability, where fire protection measures can be undertaken in advance. In order to test the effectiveness of this approach, this approach has been applied to the NPA of Torre Guaceto (Apulia Region, southern Italy). The most fire vulnerable areas are the patch of century-old forest characterized by high sensitivity and stress, and the wetlands and century-old olive groves due to their high sensitivity. The GIS fuzzy expert system provides evidence of its potential usefulness for the effective management of natural protected areas and can help conservation managers to plan and intervene in order to mitigate the fire vulnerability in accordance with conservation goals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites

    International Nuclear Information System (INIS)

    Nowak, J.Z.; Arbilla, S.; Langer, S.Z.; Dahl, S.G.

    1990-01-01

    Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3 H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3 H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors

  13. Zooplankton diversity of a protected and vulnerable wetland system in southern South America (Llancanelo area, Argentina

    Directory of Open Access Journals (Sweden)

    D. Sabina D’Ambrosio

    2016-02-01

    Full Text Available Abstract In arid regions, climatic conditions exert a great control on the aquatic systems present, but recent changes in climate have produced an enhanced salinization of the aquatic environments located there. Consequently, a major reduction in biodiversity would be expected in those wetlands that were originally fresh water. Salinity is a principal cause of reduced biodiversity particularly in zooplankton because few of those species can adapt to the salt pressure of saline environments. Therefore, the aim of this study was to gain essential information on the diversity of aquatic invertebrates in Llancanelo basin by focussing the analysis on the zooplankton community and exploring seasonal and spatial differences in the zooplankton assemblages of this vulnerable wetland system within an arid region of Argentina. Seasonal samples were taken at nine sites in the basin (a shallow lake, 4 springs, streams, and the Malargüe River. A total of 45 species were identified. The zooplankton abundance in the lake displayed a clear seasonal contrast and was higher than that recorded in the springs and lotic environments. Boeckella poopoensis, Fabrea salina, and Brachionus plicatilis predominated in the lake, indicating their halophilia. The presence of the crustaceans Alona sp., Macrocyclops albidus, and Paracyclops fimbriatus was restricted to the springs; whereas Notholca labis and Notholca squamula were found only in running water. The zooplankton species richness in the Llancanelo area is low because of both the salt content in the lake and the irregularity of freshwater entry in all locations during the annual cycle.

  14. Vulnerability assessment of a space based weapon platform electronic system exposed to a thermonuclear weapon detonation

    Science.gov (United States)

    Perez, C. L.; Johnson, J. O.

    Rapidly changing world events, the increased number of nations with inter-continental ballistic missile capability, and the proliferation of nuclear weapon technology will increase the number of nuclear threats facing the world today. Monitoring these nation's activities and providing an early warning and/or intercept system via reconnaissance and surveillance satellites and space based weapon platforms is a viable deterrent against a surprise nuclear attack. However, the deployment of satellite and weapon platform assets in space will subject the sensitive electronic equipment to a variety of natural and man-made radiation environments. These include Van Allen Belt protons and electrons; galactic and solar flare protons; and neutrons, gamma rays, and x-rays from intentionally detonated fission and fusion weapons. In this paper, the MASH vl.0 code system is used to estimate the dose to the critical electronics components of an idealized space based weapon platform from neutron and gamma-ray radiation emitted from a thermonuclear weapon detonation in space. Fluence and dose assessments were performed for the platform fully loaded, and in several stages representing limited engagement scenarios. The results indicate vulnerabilities to the Command, Control, and Communication bay instruments from radiation damage for a nuclear weapon detonation for certain source/platform orientations. The distance at which damage occurs will depend on the weapon yield (n,(gamma)/kiloton) and size (kilotons).

  15. Food system sustainability and vulnerability: food acquisition during the military occupation of Kuwait.

    Science.gov (United States)

    Alajmi, Fahhad; Somerset, Shawn M

    2015-11-01

    To document food acquisition experiences during Iraqi military occupation in Kuwait. Retrospective cross-sectional study. Urban areas in Kuwait during occupation. Those living in Kuwait during the period of occupation, and aged between 15 to 50 years at the time of occupation, recruited by snowball sampling. A total of 390 completed questionnaires (response rate 78%, 202 female and 188 male) were returned. During the occupation, food became increasingly difficult to acquire. Two food systems emerged: (i) an underground Kuwaiti network linked to foods recovered from local food cooperatives and (ii) a black market supplied by food imported through Iraq or stolen locally. Food shortages led to reductions in meal size and frequency. Some respondents (47·7%) reported not having sufficient income to purchase food and 22·1% had to sell capital items to purchase food. There was a significant increase (Pbehaviour change. Respondents reported deterioration in the quality and availability of fish, milk, and fruit in particular. Despite a decrease in opportunities for physical activity, most respondents reported that they lost weight during the occupation. Although the Kuwaiti population fell by about 90 % and domestic food production increased during the 7-month occupation, the local population continued to rely heavily on imported food to meet population needs. The high prevalence of self-reported weight loss indicates the inadequacies of this food supply. High apparent food security in systems which significantly exceed the ecological carrying capacity of the local environment and rely on mass food importation remains vulnerable.

  16. Fetal alcohol programming of hypothalamic proopiomelanocortin system by epigenetic mechanisms and later life vulnerability to stress.

    Science.gov (United States)

    Bekdash, Rola; Zhang, Changqing; Sarkar, Dipak

    2014-09-01

    Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of the hypothalamic-pituitary-adrenal (HPA) axis, immune functions, and energy homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene expression, a decrement in the levels of its derived peptide β-endorphin and a dysregulation of the stress response in the adult offspring. The HPA axis is a major neuroendocrine system with pivotal physiological functions and mode of regulation. This system has been shown to be perturbed by prenatal alcohol exposure. It has been demonstrated that the perturbation of the HPA axis by FAE is long-lasting and is linked to molecular, neurophysiological, and behavioral changes in exposed individuals. Recently, we showed that the dysregulation of the POMC system function by FAE is induced by epigenetic mechanisms such as hypermethylation of Pomc gene promoter and an alteration in histone marks in POMC neurons. This developmental programming of the POMC system by FAE altered the transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood. These long-lasting epigenetic changes influenced subsequent generations via the male germline. We also demonstrated that the epigenetic programming of the POMC system by FAE was reversed in adulthood with the application of the inhibitors of DNA methylation or histone modifications. Thus, prenatal environmental influences, such as alcohol exposure, could epigenetically modulate POMC neuronal circuits and function to shape adult behavioral patterns. Identifying specific epigenetic factors in hypothalamic POMC neurons that are modulated by fetal alcohol and target Pomc gene could be potentially useful for the development of new therapeutic approaches to treat stress-related diseases in patients with fetal alcohol spectrum disorders. Copyright © 2014 by the Research Society on Alcoholism.

  17. Early social deprivation impairs pair bonding and alters serum corticosterone and the NAcc dopamine system in mandarin voles.

    Science.gov (United States)

    Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo

    2013-12-01

    Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Vulnerability classification in man-land territorial system of mining cities based on triangle methodology

    Energy Technology Data Exchange (ETDEWEB)

    Xin Xin; Ping-Yu Zhang [Chinese Academy of Sciences, Changchun (China). Northeast Institute of Geography and Agricultural Ecology

    2009-02-15

    The vulnerabilities of 40 mining cities were classified into 6 types by triangle methodology and corresponding sustainable development suggestions were proposed. Most mining cities in east China are: resource and environment and social (RS) type and economy, resource, environment and social (ERS) type, with low vulnerability. In central China, most mining cities are economy and resource and environment (ER), RS and ERS types. The vulnerability in most west mining cities is high. Coal mining cities are mostly ER, RS and ERS types, while metal mining cities are almost ERS type. 11 refs., 4 figs., 3 tabs.

  19. 25-Hydroxyvitamin D depletion does not exacerbate MPTP-induced dopamine neuron damage in mice.

    Directory of Open Access Journals (Sweden)

    E Danielle Dean

    Full Text Available Recent clinical evidence supports a link between 25-hydroxyvitamin D insufficiency (serum 25-hydroxyvitamin D [25(OHD] levels <30 ng/mL and Parkinson's disease. To investigate the effect of 25(OHD depletion on neuronal susceptibility to toxic insult, we induced a state of 25(OHD deficiency in mice and then challenged them with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. We found there was no significant difference between control and 25(OHD-deficient animals in striatal dopamine levels or dopamine transporter and tyrosine hydroxylase expression after lesioning with MPTP. Additionally, we found no difference in tyrosine hydroxylase expression in the substantia nigra pars compacta. Our data suggest that reducing 25(OHD serum levels in mice has no effect on the vulnerability of nigral dopaminergic neurons in vivo in this model system of parkinsonism.

  20. A Vulnerability Assessment of the U.S. Small Business B2C E-Commerce Network Systems

    Science.gov (United States)

    Zhao, Jensen J.; Truell, Allen D.; Alexander, Melody W.; Woosley, Sherry A.

    2011-01-01

    Objective: This study assessed the security vulnerability of the U.S. small companies' business-to-consumer (B2C) e-commerce network systems. Background: As the Internet technologies have been changing the way business is conducted, the U.S. small businesses are investing in such technologies and taking advantage of e-commerce to access global…

  1. VTA GABA neurons modulate specific learning behaviours through the control of dopamine and cholinergic systems

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

    Full Text Available The mesolimbic reward system is primarily comprised of the ventral tegmental area (VTA and the nucleus accumbens (NAc as well as their afferent and efferent connections. This circuitry is essential for learning about stimuli associated with motivationally-relevant outcomes. Moreover, addictive drugs affect and remodel this system, which may underlie their addictive properties. In addition to DA neurons, the VTA also contains approximately 30% ɣ-aminobutyric acid (GABA neurons. The task of signalling both rewarding and aversive events from the VTA to the NAc has mostly been ascribed to DA neurons and the role of GABA neurons has been largely neglected until recently. GABA neurons provide local inhibition of DA neurons and also long-range inhibition of projection regions, including the NAc. Here we review studies using a combination of in vivo and ex vivo electrophysiology, pharmacogenetic and optogenetic manipulations that have characterized the functional neuroanatomy of inhibitory circuits in the mesolimbic system, and describe how GABA neurons of the VTA regulate reward and aversion-related learning. We also discuss pharmacogenetic manipulation of this system with benzodiazepines (BDZs, a class of addictive drugs, which act directly on GABAA receptors located on GABA neurons of the VTA. The results gathered with each of these approaches suggest that VTA GABA neurons bi-directionally modulate activity of local DA neurons, underlying reward or aversion at the behavioural level. Conversely, long-range GABA projections from the VTA to the NAc selectively target cholinergic interneurons (CINs to pause their firing and temporarily reduce cholinergic tone in the NAc, which modulates associative learning. Further characterization of inhibitory circuit function within and beyond the VTA is needed in order to fully understand the function of the mesolimbic system under normal and pathological conditions.

  2. Contributions of dopamine-related genes and environmental factors to highly sensitive personality: a multi-step neuronal system-level approach.

    Directory of Open Access Journals (Sweden)

    Chunhui Chen

    Full Text Available Traditional behavioral genetic studies (e.g., twin, adoption studies have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP. 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001. Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional

  3. Vulnerability assessment as a missing part of efficient regulatory emergency preparedness system for nuclear critical infrastructure

    International Nuclear Information System (INIS)

    Kostadinov, V.

    2007-01-01

    One introduces a new model to assess the vulnerability of the nuclear infrastructure critical facilities. The new procedure of the vulnerability assessment (the VA) aims to reevaluate the efficiency of the present-day safeguards. On the basis of deeper insight into the VA new strategy and of the elaborated procedure to analyze the hazards for the nuclear power facilities one recommends the key safeguards affecting the damage magnitude [ru

  4. Adaptation, Spatial Heterogeneity, and the Vulnerability of Agricultural Systems to Climate Change and CO2 Fertilization: An Integrated Assessment Approach

    International Nuclear Information System (INIS)

    Antle, J.M.; Capalbo, S.M.; Elliott, E.T.; Paustian, K.H.

    2004-01-01

    In this paper we develop economic measures of vulnerability to climate change with and without adaptation in agricultural production systems. We implement these measures using coupled, site-specific ecosystem and economic simulation models. This modeling approach has two key features needed to study the response of agricultural production systems to climate change: it represents adaptation as an endogenous, non-marginal economic response to climate change; and it provides the capability to represent the spatial variability in bio-physical and economic conditions that interact with adaptive responses. We apply this approach to the dryland grain production systems of the Northern Plains region of the United States. The results support the hypothesis that the most adverse impacts on net returns distributions tend to occur in the areas with the poorest resource endowments and when mitigating effects of CO2 fertilization and adaptation are absent. We find that relative and absolute measures of vulnerability depend on complex interactions between climate change, CO2 level, adaptation, and economic conditions such as relative output prices. The relationship between relative vulnerability and resource endowments varies with assumptions about climate change, adaptation, and economic conditions. Vulnerability measured with respect to an absolute threshold is inversely related to resource endowments in all cases investigated

  5. Hazard, Vulnerability and Capacity Mapping for Landslides Risk Analysis using Geographic Information System (GIS)

    Science.gov (United States)

    Sari, D. A. P.; Innaqa, S.; Safrilah

    2017-06-01

    This research analyzed the levels of disaster risk in the Citeureup sub-District, Bogor Regency, West Java, based on its potential hazard, vulnerability and capacity, using map to represent the results, then Miles and Huberman analytical techniques was used to analyze the qualitative interviews. The analysis conducted in this study is based on the concept of disaster risk by Wisner. The result shows that the Citeureup sub-District has medium-low risk of landslides. Of the 14 villages, three villages have a moderate risk level, namely Hambalang, Tajur, and Tangkil, or 49.58% of the total land area. Eleven villages have a low level of risk, namely Pasir Mukti, Sanja, Tarikolot, Gunung Sari, Puspasari, East Karang Asem, Citeureup, Leuwinutug, Sukahati, West Karang Asem West and Puspanegara, or 48.68% of the total land area, for high-risk areas only around 1.74%, which is part of Hambalang village. The analysis using Geographic Information System (GIS) prove that areas with a high risk potential does not necessarily have a high level of risk. The capacity of the community plays an important role to minimize the risk of a region. Disaster risk reduction strategy is done by creating a safe condition, which intensified the movement of disaster risk reduction.

  6. Vulnerability of the Tibetan Pastoral Systems to Climate and Global Change

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2014-12-01

    Full Text Available The impacts of climate and global change on Tibetan pastoral systems have become increasingly evident. Thus, a significant research endeavor is to explore the combined effects of these changes on the livelihoods of herder households and communities, on the adaptation strategies they adopted to respond to the current and expected risks associated with these changes, and on the emerging opportunities that can strengthen their resilience and adaptive capacity. We performed an integrated analysis of the dynamics of Tibetan pastoral systems influenced by climate and global changes by using the analytical framework developed by Ostrom. Climate and global changes have significantly altered the attributes of and the interactions within Tibetan pastoral systems, thus posing great challenges to their sustainable development. We used Nagqu County, a remote area of the northern Tibetan Plateau of China, as a case study to analyze the adaptation strategies adopted by local herders to respond to multiple stressors, as well as the emerging opportunities that they can take advantage of to increase their adaptive capacity. Findings show that although local herders have developed various adaptation strategies, such as planting forage grass, buying fodder from the market, renting pastures, joining formal or informal cooperatives, and diversifying livelihoods, social, cultural, and institutional challenges still exist. To enhance the adaptive capacity of herders and to reduce their vulnerability, we recommend that future rangeland policies and programs promote: (1 comprehensive support for formal or informal pastoral cooperatives, (2 development of the rangeland economy to take advantage of the multifunctionalities of rangeland ecosystems, and (3 revitalization of the mobility paradigm to allow the flexible use of rangelands.

  7. An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction

    OpenAIRE

    Flagel, Shelly B; Robinson, Terry E; Clark, Jeremy J; Clinton, Sarah M; Watson, Stanley J; Seeman, Phillip; Phillips, Paul E M; Akil, Huda

    2009-01-01

    Rats selectively bred based on high or low reactivity to a novel environment were characterized for other behavioral and neurobiological traits thought to be relevant to addiction vulnerability. The two lines of animals, which differ in their propensity to self-administer drugs, also differ in the value they attribute to cues associated with reward, in impulsive behavior, and in their dopamine system. When a cue was paired with food or cocaine reward bred high-responder rats (bHRs) learned to...

  8. Developing a National Climate Indicators System to Track Climate Changes, Impacts, Vulnerabilities, and Preparedness

    Science.gov (United States)

    Kenney, M. A.; Janetos, A. C.; Arndt, D.; Chen, R. S.; Pouyat, R.; Anderson, S. M.

    2013-12-01

    The National Climate Assessment (NCA) is being conducted under the auspices of the U.S. Global Change Research Program (USGCRP), pursuant to the Global Change Research Act of 1990, Section 106, which requires a report to Congress every 4 years. Part of the vision, which is now under development, for the sustained National Climate Assessment (NCA) process is a system of physical, ecological, and societal indicators that communicate key aspects of the physical climate, climate impacts, vulnerabilities, and preparedness for the purpose of informing both decision makers and the public with scientifically valid information that is useful to inform decision-making processes such as the development and implementation of climate adaptation strategies in a particular sector or region. These indicators will be tracked as a part of ongoing assessment activities, with adjustments as necessary to adapt to changing conditions and understanding. The indicators will be reviewed and updated so that the system adapts to new information. The NCA indicator system is not intended to serve as a vehicle for documenting rigorous cause and effect relationships. It is reasonable, however, for it to serve as a guide to those factors that affect the evolution of variability and change in the climate system, the resources and sectors of concern that are affected by it, and how society chooses to respond. Different components of the end-to-end climate issue serve as categories within which to organize an end-to-end system of indicators: Greenhouse Gas Emissions and Sinks, Atmospheric Composition, Physical Climate Variability and Change, Sectors and Resources of Concern, and Adaptation and Mitigation Responses. This framing has several advantages. It can be used to identify the different components of the end-to-end climate issue that both decision-makers and researchers are interested in. It is independent of scale, and therefore allows the indicators themselves to be described at spatial

  9. The possible interaction of dopamine system in nucleus accumbens shell and glutamate system of prelimbic region on locomotor activity in rat

    Directory of Open Access Journals (Sweden)

    Hatam Ahmadi

    2013-06-01

    Full Text Available Background: Nucleus accumbens (NAc and prefrontal cortex (PFC dopaminergic and glutamatergic systems are involved in regulating of locomotor activity behaviors. This study has investigated the interaction of NAc shell dopaminergic system and prelimbic glutamatergic systems in regulating locomotor activity and related parameters. Methods: The aim of this study was the effect the drugs injection interaction in the brain of male Wistar rats on locomotor activity and related parameters, in the order of this purpose, open field apparatus that automatically recorded locomotor activity was employed. Unilateral intra-cerebral injection of drugs was done. Results: Unilateral intra-prelimbic injection of D-AP7 (N-methyl-D-aspartic acid= NMDA receptor antagonist; 0.25, 0.5 and 1μg/μl did not alter locomotor activity behaviors. However, infusion of NMDA (0.9μg/μl in this region increased locomotor activity (P<0.01, whereas decreased rearing (P<0.01 and grooming (P<0.01 which was blocked by D-AP7 (0.25μg/μl (P<0.01. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1μg/μl into the left NAc shell did not alter locomotor activity. However, injection of SKF38393 (dopamine D1 receptor agonist; 4μg/μl into the left NAc shell increased locomotor activity (P<0.05 which was blocked by SCH23390 (0.25μg/μl (P<0.01. Furthermore, the subthreshold dose infusion of SCH23390 (0.25μg/μl into the left NAc shell reduced the effect of intra- prelimbic NMDA on locomotor activity (P<0.01. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1μg/μl potentiated the middle dose (P<0.05, whereas decreased the higher dose of intra-left prelimbic NMDA response (P<0.05 on locomotor activity. Conclusion: The results suggested a modulatory effect of the NAc shell dopaminergic system on increased locomotor activity by activating glutamate system in prelimbic.

  10. Developing a System of National Climate Assessment Indicators to Track Climate Change Impacts, Vulnerabilities, and Preparedness

    Science.gov (United States)

    Janetos, A. C.; Kenney, M. A.; Chen, R. S.; Arndt, D.

    2012-12-01

    The National Climate Assessment (NCA) is being conducted under the auspices of the U.S. Global Change Research Program (USGCRP), pursuant to the Global Change Research Act of 1990, Section 106, which requires a report to Congress every 4 years (http://globalchange.gov/what-we-do/assessment/). Part of the vision for the sustained National Climate Assessment (NCA) process is a system of physical, ecological, and societal indicators that communicate key aspects of the physical climate, climate impacts, vulnerabilities, and preparedness for the purpose of informing both decision makers and the public with scientifically valid information that is useful to inform decision-making processes such as the development and implementation of climate adaptation strategies in a particular sector or region. These indicators will be tracked as a part of ongoing assessment activities, with adjustments as necessary to adapt to changing conditions and understanding. The indicators will be reviewed and updated so that the system adapts to new information. The NCA indicator system is not intended to serve as a vehicle for documenting rigorous cause and effect relationships. It is reasonable, however, for it to serve as a guide to those factors that affect the evolution of variability and change in the climate system, the resources and sectors of concern that are affected by it, and how society chooses to respond. Different components of the end-to-end climate issue serve as categories within which to organize an end-to-end system of indicators: Greenhouse Gas Emissions and Sinks Atmospheric Composition Physical Climate Variability and Change Sectors and Resources of Concern Adaptation and Mitigation Responses This framing has several advantages. It can be used to identify the different components of the end-to-end climate issue that both decision-makers and researchers are interested in. It is independent of scale, and therefore allows the indicators themselves to be described at

  11. A Multi-area Model of a Physical Protection System for a Vulnerability Assessment

    International Nuclear Information System (INIS)

    Jang, Sung Soon; Yoo, Ho Sik

    2008-01-01

    A physical protection system (PPS) integrates people, procedures and equipment for the protection of assets or facilities against theft, sabotage or other malevolent human attacks. Among critical facilities, nuclear facilities and nuclear weapon sites require the highest level of PPS. After the September 11, 2001 terrorist attacks, international communities, including the IAEA, have made substantial efforts to protect nuclear material and nuclear facilities. These efforts include the Nuclear Security Fund established by the IAEA in 2002 and the Global Initiative to Combat Nuclear Terrorism which is launched by the USA and Russia in 2006. Without a regular assessment, the PPS might waste valuable resources on unnecessary protection or, worse yet, fail to provide adequate protection at critical points of a facility. Due to the complexity of protection systems, the assessment usually requires computer modeling techniques. Several Codes were developed to model and analyze a PPS. We also devised and implemented new analysis method and named it as Systematic Analysis of physical Protection Effectiveness (SAPE). A SAPE code consumes much time to analyze a PPS over a large area in detail. It is because SAPE uses meshes of an equal size for the analysis of a 2D map. The analysis is more accurate when the meshes of a smaller size are used. However, the analysis time is roughly proportional to the exponential of the number of meshes. Thus, the speed and accuracy is in a trade-off relation. In the paper, we suggest a multi-area model of a PPS for a vulnerability assessment to solve this problem. Using multi areas with different scales, we can accurately analyze a PPS near a target and can analyze it over a large area rather roughly

  12. Quantitative assessment of key parameters in qualitative vulnerability methods applied in karst systems based on an integrated numerical modelling approach

    Science.gov (United States)

    Doummar, Joanna; Kassem, Assaad

    2017-04-01

    In the framework of a three-year PEER (USAID/NSF) funded project, flow in a Karst system in Lebanon (Assal) dominated by snow and semi arid conditions was simulated and successfully calibrated using an integrated numerical model (MIKE-She 2016) based on high resolution input data and detailed catchment characterization. Point source infiltration and fast flow pathways were simulated by a bypass function and a high conductive lens respectively. The approach consisted of identifying all the factors used in qualitative vulnerability methods (COP, EPIK, PI, DRASTIC, GOD) applied in karst systems and to assess their influence on recharge signals in the different hydrological karst compartments (Atmosphere, Unsaturated zone and Saturated zone) based on the integrated numerical model. These parameters are usually attributed different weights according to their estimated impact on Groundwater vulnerability. The aim of this work is to quantify the importance of each of these parameters and outline parameters that are not accounted for in standard methods, but that might play a role in the vulnerability of a system. The spatial distribution of the detailed evapotranspiration, infiltration, and recharge signals from atmosphere to unsaturated zone to saturated zone was compared and contrasted among different surface settings and under varying flow conditions (e.g., in varying slopes, land cover, precipitation intensity, and soil properties as well point source infiltration). Furthermore a sensitivity analysis of individual or coupled major parameters allows quantifying their impact on recharge and indirectly on vulnerability. The preliminary analysis yields a new methodology that accounts for most of the factors influencing vulnerability while refining the weights attributed to each one of them, based on a quantitative approach.

  13. Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated (2-D-penicillamine, 5-D-penicillamine)enkephalin ( sup 125 I-DPDPE)

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P.; Kalivas, P.W. (Washington State Univ., Pullman (USA))

    1990-01-01

    The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.

  14. How urban system vulnerabilities to flooding could be assessed to improve resilience and adaptation in spatial planning

    Science.gov (United States)

    Pasi, Riccardo; Viavattene, Christophe; La Loggia, Goffredo

    2016-04-01

    Natural hazards damage assets and infrastructure inducing disruptions to urban functions and key daily services. These disruptions may be short or long with a variable spatial scale of impact. From an urban planning perspective, measuring these disruptions and their consequences at an urban scale is fundamental in order to develop more resilient cities. Whereas the assessment of physical vulnerabilities and direct damages is commonly addressed, new methodologies for assessing the systemic vulnerability at the urban scale are required to reveal these disruptions and their consequences. Physical and systemic vulnerability should be measured in order to reflect the multifaceted fragility of cities in the face of external stress, both in terms of the natural/built environment and socio-economic sphere. Additionally, a systemic approach allows the consideration of vulnerability across different spatial scales, as impacts may vary and be transmitted across local, regional or national levels. Urban systems are spatially distributed and the nature of this can have significant effects on flood impacts. The proposed approach identifies the vulnerabilities of flooding within urban contexts, including both in terms of single elementary units (buildings, infrastructures, people, etc.) and systemic functioning (urban functions and daily life networks). Direct losses are appraised initially using conventional methodologies (e.g. depth-damage functions). This aims to both understand the spatial distribution of physical vulnerability and associated losses and, secondly, to identify the most vulnerable building types and ways to improve the physical adaptation of our cities, proposing changes to building codes, design principles and other municipal regulation tools. The subsequent systemic approach recognises the city as a collection of sub-systems or functional units (such as neighbourhoods and suburbs) providing key daily services for inhabitants (e.g. healthcare facilities

  15. Study of groundwater vulnerability to pollution using the DRASTIC method coupled with a geographic information system (GIS): application to groundwater Beni Amir, Morocco

    Science.gov (United States)

    Knouz, Najat; Boudhar, Abdelghani; Bachaoui, El Mostafa

    2016-04-01

    Fresh water is the condition of all life on Earth for its vital role in the survival of living beings and in the social, economic and technological development. The Groundwater, as the surface water, is increasingly threatened by agricultural and industrial pollution. In this respect, the groundwater vulnerability assessment to pollution is a very valuable tool for resource protection, management of its quality and uses it in a sustainable way. The main objective of this study is the evaluation of groundwater vulnerability to pollution of the study area, Beni Amir, located in the first irrigated perimeter of Morocco, Tadla, using the DRASTIC method (depth to water, net recharge, aquifer media, soil media, Topography, impact of Vadose zone and hydraulic conductivity), and assessing the impact of each parameter on the DRASTIC vulnerability index by a sensitivity analysis. This study also highlights the role of geographic information systems (GIS) in assessing vulnerability. The Vulnerability index is calculated as the sum of product of ratings and weights assigned to each of the parameter DRASTIC. The results revealed four vulnerability classes, 7% of the study area has a high vulnerability, 31% are moderately vulnerable, 57% have a low vulnerability and 5% are of very low vulnerability.

  16. The roles of dopamine and serotonin in decision making: evidence from pharmacological experiments in humans.

    Science.gov (United States)

    Rogers, Robert D

    2011-01-01

    Neurophysiological experiments in primates, alongside neuropsychological and functional magnetic resonance investigations in humans, have significantly enhanced our understanding of the neural architecture of decision making. In this review, I consider the more limited database of experiments that have investigated how dopamine and serotonin activity influences the choices of human adults. These include those experiments that have involved the administration of drugs to healthy controls, experiments that have tested genotypic influences upon dopamine and serotonin function, and, finally, some of those experiments that have examined the effects of drugs on the decision making of clinical samples. Pharmacological experiments in humans are few in number and face considerable methodological challenges in terms of drug specificity, uncertainties about pre- vs post-synaptic modes of action, and interactions with baseline cognitive performance. However, the available data are broadly consistent with current computational models of dopamine function in decision making and highlight the dissociable roles of dopamine receptor systems in the learning about outcomes that underpins value-based decision making. Moreover, genotypic influences on (interacting) prefrontal and striatal dopamine activity are associated with changes in choice behavior that might be relevant to understanding exploratory behaviors and vulnerability to addictive disorders. Manipulations of serotonin in laboratory tests of decision making in human participants have provided less consistent results, but the information gathered to date indicates a role for serotonin in learning about bad decision outcomes, non-normative aspects of risk-seeking behavior, and social choices involving affiliation and notions of fairness. Finally, I suggest that the role played by serotonin in the regulation of cognitive biases, and representation of context in learning, point toward a role in the cortically mediated cognitive

  17. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  18. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  19. Design of Service Oriented Architecture(SOA)-based Software Vulnerability Analysis Method for Digital I and C System in NPP

    International Nuclear Information System (INIS)

    Song, J. G.; Lee, C. K.; Kwon, K. C.; Kim, K. H.; Kim, S. S.

    2011-01-01

    Diverse cyber security issues due to the vulnerability of the digital control systems have been brought up in the existing IT environments while advancement and propagation of digital I and C systems have improved convenience through automation. The recent example of Stuxnet proved that stability in the digital I and C system could not be secured due to an air gap of physical security elements. Therefore, it is required to discover new approaches toward cyber security that will overcome the limitation on security in a closed environment. In particular, there is a rapid increase in the importance of cyber security seen in guidelines published by IAEA and U.S. NRC shows that cyber security as well as physical security draws worldwide attention as a key component for nuclear system safety. To incorporate the new guide requirement, cyber security threats are analyzed by ITbase security elements for finding best practice approaches. The vulnerabilities identified by the general security threats and defined mitigation activities can include many different methods and strategies. This research suggests a method for analyzing vulnerability and assessment the nuclear digital I and C cyber security

  20. Design of Service Oriented Architecture(SOA)-based Software Vulnerability Analysis Method for Digital I and C System in NPP

    Energy Technology Data Exchange (ETDEWEB)

    Song, J. G.; Lee, C. K.; Kwon, K. C. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, K. H. [Shinsegae Information and Communication Co., Seoul (Korea, Republic of); Kim, S. S. [Hannam University, Daejeon (Korea, Republic of)

    2011-05-15

    Diverse cyber security issues due to the vulnerability of the digital control systems have been brought up in the existing IT environments while advancement and propagation of digital I and C systems have improved convenience through automation. The recent example of Stuxnet proved that stability in the digital I and C system could not be secured due to an air gap of physical security elements. Therefore, it is required to discover new approaches toward cyber security that will overcome the limitation on security in a closed environment. In particular, there is a rapid increase in the importance of cyber security seen in guidelines published by IAEA and U.S. NRC shows that cyber security as well as physical security draws worldwide attention as a key component for nuclear system safety. To incorporate the new guide requirement, cyber security threats are analyzed by ITbase security elements for finding best practice approaches. The vulnerabilities identified by the general security threats and defined mitigation activities can include many different methods and strategies. This research suggests a method for analyzing vulnerability and assessment the nuclear digital I and C cyber security

  1. Adapting a commercial power system simulator for smart grid based system study and vulnerability assessment

    Science.gov (United States)

    Navaratne, Uditha Sudheera

    The smart grid is the future of the power grid. Smart meters and the associated network play a major role in the distributed system of the smart grid. Advance Metering Infrastructure (AMI) can enhance the reliability of the grid, generate efficient energy management opportunities and many innovations around the future smart grid. These innovations involve intense research not only on the AMI network itself but as also on the influence an AMI network can have upon the rest of the power grid. This research describes a smart meter testbed with hardware in loop that can facilitate future research in an AMI network. The smart meters in the testbed were developed such that their functionality can be customized to simulate any given scenario such as integrating new hardware components into a smart meter or developing new encryption algorithms in firmware. These smart meters were integrated into the power system simulator to simulate the power flow variation in the power grid on different AMI activities. Each smart meter in the network also provides a communication interface to the home area network. This research delivers a testbed for emulating the AMI activities and monitoring their effect on the smart grid.

  2. Mangrove vulnerability index using GIS

    Science.gov (United States)

    Yunus, Mohd Zulkifli Mohd; Ahmad, Fatimah Shafinaz; Ibrahim, Nuremira

    2018-02-01

    Climate change, particularly its associated sea level rise, is major threat to mangrove coastal areas, and it is essential to develop ways to reduce vulnerability through strategic management planning. Environmental vulnerability can be understood as a function of exposure to impacts and the sensitivity and adaptive capacity of ecological systems towards environmental tensors. Mangrove vulnerability ranking using up to 14 parameters found in study area, which is in Pulau Kukup and Sg Pulai, where 1 is low vulnerability and 5 is very high vulnerability. Mangrove Vulnerability Index (MVI) is divided into 3 main categories Physical Mangrove Index (PMI), Biological Mangrove Index (BMI) and Hazard Mangrove Index (HMI).

  3. Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

    Science.gov (United States)

    Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

    2017-11-01

    Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

  4. The Naples High- and Low-Excitability rats: selective breeding, behavioral profile, morphometry, and molecular biology of the mesocortical dopamine system.

    Science.gov (United States)

    Viggiano, Davide; Vallone, Daniela; Welzl, Hans; Sadile, Adolfo G

    2002-09-01

    The Naples High- (NHE) and Low-Excitability (NLE) rat lines have been selected since 1976 on the basis of behavioral arousal to novelty (Làt-maze). Selective breeding has been conducted under continuous genetic pressure, with no brother-sister mating. The behavioral analyses presented here deal with (1) activity in environments of different complexity, i.e., holeboard and Làt maze; (2) maze learning in hexagonal tunnel, Olton, and Morris water mazes and; (3) two-way active avoidance and conditioned taste aversion tests. Morphometric analyses deal with central dopaminergic systems at their origin and target sites, as well as the density of dopamine transporter immunoreactivity. Molecular biology analyses are also presented, dealing with recent experiments on the prefrontal cortex (PFc), cloning and identifying differentially expressed genes using subtractive libraries and RNAase protection. The divergence between NLE and NHE rats varies as a function of the complexity level of the environment, with an impaired working and reference memory in both lines compared to random bred (NRB) controls. Moreover, data from the PFc of NHE rats show a hyperdopaminergic innervation, with overexpression of mRNA species involved in basal metabolism, and down-regulation of dopamine D1 receptors. Altogether, the evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.

  5. Core damage vulnerability due to the loss of ESW [essential service water] systems at multiplant sites: An assessment and options

    International Nuclear Information System (INIS)

    Kohut, P.; Musicki, Z.; Fitzpatrick, R.

    1989-01-01

    The main objective of this study is to establish the core damage vulnerability caused by the failure of the ESW systems in multiplant units that have only two sw pumps per unit with crosstie capability. Design and operating data have been surveyed to derive system failure frequency. A core damage model is constructed including operating configurations, specific recovery actions, and time and leak rate dependent RCP seal LOCA model. The estimated CDF SW = 2.55 x 10 -4 /yr is significant indicating the potential vulnerability of this particular SW design arrangement. A number of different potential improvements have been considered. The addition of a swing pump serving both units is shown to have the most significant CDF reduction potential (∼50%) combined with advantageous cost/benefit aspects. 2 refs., 2 tabs

  6. Numerical modeling of ADA system for vulnerable road users protection based on radar and vision sensing

    NARCIS (Netherlands)

    Garate, V.R.; Bours, R.C.H.; Kietlinski, K.

    2012-01-01

    The protection of vulnerable road users (VRU) remains one of the most challenging problems for our society and several governmental and consumer organization has set targets to reduce the VRU fatality and injury rates. The automotive industry is, therefore, developing pedestrian and cyclist

  7. Evaluation of intrinsic groundwater vulnerability to pollution: COP method for pilot area of Carrara hydrogeological system (Northern Tuscany, Italy)

    Science.gov (United States)

    Baldi, B.; Guastaldi, E.; Rossetto, R.

    2009-04-01

    During the characterization of the Apuan Alps groundwater body ( "Corpo Idrico Sotterraneo Significativo", briefly CISS) (Regione Toscana, 2007) the intrinsic vulnerability has been evaluated for Carrara hydrogeological system (Northern Tuscany, Italy) by means of COP method, developed within COST 620 European Action (Zwalhlen, 2003). This system is both characterized by large data availability and it is considered an highly risky zone since groundwater protection problems (turbidity of the tapped spring waters and hydrocarbons contamination) and anthropic activity (marble quarries). The study area, 20 Km2large, has high relief energy, with elevations ranging from 5 to 1700 m amsl in almost 5 km. Runoff is scarce except during heavy rainfall; due to the presence of carbonate rocks infiltration is high: groundwater discharge at 155-255 m amsl. The area is located in the north-western part of Apuan Alps Metamorphic Complex, characterized by carbonate and non-carbonate rocks belonging to the non-metamorphic Tuscan Units (Carnic-Oligocene), Mesozoic Succession, Middle-Triassic Succession, and metamorphic Paleozoic rocks. The main geological structure of the area is the Carrara Syncline, constituted prevalently by dolostones, marbles and cherty limestones. These carbonate formations define several moderately to highly productive hydrogeological units, characterized by fissured and karst flow. Hydrogeological system may be subdivided in two different subsets, because of both geo-structural set up and area conformation. However, these are hydrogeologically connected since anisotropy and fractures of karst groundwater. The southern boundary of Carrara hydrogeological system shows important dammed springs, defined by low productive units of Massa Unit (Cambriano?-Carnic). COP methodology for evaluating intrinsic vulnerability of karst groundwater is based on three main factors for the definition of vulnerability itself: COPIndex = C (flow Concentration) *O (Overlying layers

  8. A Bottom-up Vulnerability Analysis of Water Systems with Decentralized Decision Making and Demographic Shifts- the Case of Jordan.

    Science.gov (United States)

    Lachaut, T.; Yoon, J.; Klassert, C. J. A.; Talozi, S.; Mustafa, D.; Knox, S.; Selby, P. D.; Haddad, Y.; Gorelick, S.; Tilmant, A.

    2016-12-01

    Probabilistic approaches to uncertainty in water systems management can face challenges of several types: non stationary climate, sudden shocks such as conflict-driven migrations, or the internal complexity and dynamics of large systems. There has been a rising trend in the development of bottom-up methods that place focus on the decision side instead of probability distributions and climate scenarios. These approaches are based on defining acceptability thresholds for the decision makers and considering the entire range of possibilities over which such thresholds are crossed. We aim at improving the knowledge on the applicability and relevance of this approach by enlarging its scope beyond climate uncertainty and single decision makers; thus including demographic shifts, internal system dynamics, and multiple stakeholders at different scales. This vulnerability analysis is part of the Jordan Water Project and makes use of an ambitious multi-agent model developed by its teams with the extensive cooperation of the Ministry of Water and Irrigation of Jordan. The case of Jordan is a relevant example for migration spikes, rapid social changes, resource depletion and climate change impacts. The multi-agent modeling framework used provides a consistent structure to assess the vulnerability of complex water resources systems with distributed acceptability thresholds and stakeholder interaction. A proof of concept and preliminary results are presented for a non-probabilistic vulnerability analysis that involves different types of stakeholders, uncertainties other than climatic and the integration of threshold-based indicators. For each stakeholder (agent) a vulnerability matrix is constructed over a multi-dimensional domain, which includes various hydrologic and/or demographic variables.

  9. Next-generation Algorithms for Assessing Infrastructure Vulnerability and Optimizing System Resilience

    Energy Technology Data Exchange (ETDEWEB)

    Burchett, Deon L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Chen, Richard Li-Yang [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Phillips, Cynthia A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Richard, Jean-Philippe [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-05-01

    This report summarizes the work performed under the project project Next-Generation Algo- rithms for Assessing Infrastructure Vulnerability and Optimizing System Resilience. The goal of the project was to improve mathematical programming-based optimization technology for in- frastructure protection. In general, the owner of a network wishes to design a network a network that can perform well when certain transportation channels are inhibited (e.g. destroyed) by an adversary. These are typically bi-level problems where the owner designs a system, an adversary optimally attacks it, and then the owner can recover by optimally using the remaining network. This project funded three years of Deon Burchett's graduate research. Deon's graduate advisor, Professor Jean-Philippe Richard, and his Sandia advisors, Richard Chen and Cynthia Phillips, supported Deon on other funds or volunteer time. This report is, therefore. essentially a replication of the Ph.D. dissertation it funded [12] in a format required for project documentation. The thesis had some general polyhedral research. This is the study of the structure of the feasi- ble region of mathematical programs, such as integer programs. For example, an integer program optimizes a linear objective function subject to linear constraints, and (nonlinear) integrality con- straints on the variables. The feasible region without the integrality constraints is a convex polygon. Careful study of additional valid constraints can significantly improve computational performance. Here is the abstract from the dissertation: We perform a polyhedral study of a multi-commodity generalization of variable upper bound flow models. In particular, we establish some relations between facets of single- and multi- commodity models. We then introduce a new family of inequalities, which generalizes traditional flow cover inequalities to the multi-commodity context. We present encouraging numerical results. We also consider the directed

  10. The Vulnerability of Earth Systems to Human-Induced Global Change and Strategies for Mitigation

    Science.gov (United States)

    Watson, R. T.

    2002-12-01

    Since the IGY, there has been growing evidence that climate is changing in response to human activities. The overwhelming majority of scientific experts, whilst recognizing that scientific uncertainties exist, nonetheless believe that human-induced climate change is inevitable. Indeed, during the last few years, many parts of the world have suffered major heat waves, floods, droughts, fires and extreme weather events leading to significant economic losses and loss of life. While individual events cannot be directly linked to human-induced climate change, the frequency and magnitude of these types of events are predicted to increase in a warmer world. The question is not whether climate will change, but rather how much (magnitude), how fast (the rate of change) and where (regional patterns). It is also clear that climate change and other human-induced modifications to the environment will, in many parts of the world, adversely affect socio-economic sectors, including water resources, agriculture, forestry, fisheries and human settlements, ecological systems (particularly forests and coral reefs), and human health (particularly diseases spread by insects), with developing countries being the most vulnerable. Environmental degradation of all types (i.e., climate change, loss of biodiversity, land degradation, air and water quality) all undermine the challenge of poverty alleviation and sustainable economic growth. One of the major challenges facing humankind is to provide an equitable standard of living for this and future generations: adequate food, water and energy, safe shelter and a healthy environment (e.g., clean air and water). Unfortunately, human-induced climate change, as well as other global environmental issues such as land degradation, loss of biological diversity and stratospheric ozone depletion, threatens our ability to meet these basic human needs. The good news is, however, that the majority of experts believe that significant reductions in net

  11. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Donald A., E-mail: dafox@uh.edu [College of Optometry, University of Houston, Houston, TX (United States); Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX (United States); Hamilton, W. Ryan [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Johnson, Jerry E. [Department of Natural Sciences, University of Houston-Downtown, Houston, TX (United States); Xiao, Weimin [College of Optometry, University of Houston, Houston, TX (United States); Chaney, Shawntay; Mukherjee, Shradha [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Miller, Diane B.; O' Callaghan, James P. [Toxicology and Molecular Biology Branch, Health Effects Research Laboratory, Centers for Disease Control and Prevention-NIOSH, Morgantown, WV USA (United States)

    2011-11-15

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1, {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black

  12. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    International Nuclear Information System (INIS)

    Fox, Donald A.; Hamilton, W. Ryan; Johnson, Jerry E.; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B.; O'Callaghan, James P.

    2011-01-01

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ∼ 25 and ∼ 40 μg/dL, respectively, on PN10 and by PN30 all were ≤ 1 μg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: ► Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: ≤ 1, ≤ 10, 25 and 40 μg/dL ► Gestational lead exposure dose-dependently decreased the number of TH

  13. Concepts and theoretical specifications of a Coastal Vulnerability Dynamic Simulator (COVUDS): A multi-agent system for simulating coastal vulnerability towards management of coastal ecosystem services

    Science.gov (United States)

    Orencio, P. M.; Endo, A.; Taniguchi, M.

    2014-12-01

    Disaster-causing natural hazards such as floods, erosions, earthquakes or slope failures were particularly observed to be concentrated in certain geographical regions. In the Asia-pacific region, coastal ecosystems were suffering because of perennial threats driven by chronic fluctuations in climate variability (e.g., typhoons, ENSO), or by dynamically occurring events (e.g., earthquakes, tsunamis). Among the many people that were found prone to such a risky condition were the ones inhabiting near the coastal areas. Characteristically, aside from being located at the forefront of these events, the coastal communities have impacted the resource by the kind of behavioral patterns they exhibited, such as overdependence and overexploitation to achieve their wellbeing. In this paper, we introduce the development of an approach to an assessment of the coupled human- environment using a multi- agent simulation (MAS) model known as Coastal Vulnerability Dynamic Simulator (COVUDS). The COVUDS comprised a human- environmental platform consisting multi- agents with corresponding spatial- based dynamic and static variables. These variables were used to present multiple hypothetical future situations that contribute to the purpose of supporting a more rational management of the coastal ecosystem and their environmental equities. Initially, we present the theoretical and conceptual components that would lead to the development of the COVUDS. These consisted of the human population engaged in behavioral patterns affecting the conditions of coastal ecosystem services; the system of the biophysical environment and changes in patches brought by global environment and local behavioral variations; the policy factors that were important for choosing area- specific interventions; and the decision- making mechanism that integrates the first three components. To guide a future scenario-based application that will be undertaken in a coastal area in the Philippines, the components of the

  14.  α-Cyclodextrin dimer complexes of dopamine and levodopa derivatives to assess drug delivery to the central nervous system: ADME and molecular docking studies

    Directory of Open Access Journals (Sweden)

    Shityakov S

    2012-06-01

    Full Text Available Sergey Shityakov, Jens Broscheit, Carola FörsterDepartment of Anesthesiology and Critical Care, University of Würzburg, Würzburg, GermanyAbstract: This paper attempts to predict and emphasize molecular interactions of dopamine, levodopa, and their derivatives (Dopimid compounds containing 2-phenyl-imidazopyridine moiety with the α-cyclodextrin dimer in order to assess and improve drug delivery to the central nervous system. The molecular docking method is used to determine the energetic profiles, hydrogen bond formation, and hydrophobic effect of 14 host–guest complexes. The results show that the “chemical branching” represented by additional ethyl-acetate residue is energetically unfavorable and promotes a conformational shift due to the high root mean square deviation levels. This phenomenon is characterized by a low number of H-bonds and a significant decrease of the host–guest hydrophobic potential surface. Finally, the overall docking procedure presents a powerful rationale for screening and analyzing various sets of promising drug-like chemical compounds in the fields of supramolecular chemistry, molecular sensing, synthetic receptors, and nanobiotechnology.Keywords: dopamine, levodopa, Dopimid compounds, α-CD dimer, molecular docking, complexation

  15. Reproductive biology and breeding system of Saraca asoca (Roxb.) De Wilde: a vulnerable medicinal plant.

    Science.gov (United States)

    Smitha, G R; Thondaiman, V

    2016-01-01

    Ashoka ( Saraca asoca ) is a perennial, evergreen tree valued for its ornamental flowers and medicinal values. This species is classified as 'vulnerable' under IUCN list due to its dwindling population because of destructive harvesting from natural habitats. Therefore, conservation and multiplication of this species is need of the hour to utilize its astonishing medicinal uses eternally. Conservation approaches of any plant species require in-depth study of its reproductive biology, which is lacking in this species. The present study is the first detailed report on reproductive biology of S. asoca . This tree bears fragrant flowers in paniculate corymbose inflorescence from December end to May, with peak flowering during February-March. The fruits attain its maturity during last week of May-July. Seeds were dispersed from the pod to the tree premises upon complete maturity. The time of anthesis in this species is noticed in the early morning from 3.00 to 5.30 am, which coincided with anther dehiscence, stigma receptivity and insect activity. The length of the stamen and pistil points towards the pollination compatibility in both male and female parts. Pollen viability was maximum within 2 h of anthesis, which decreased thereafter and no pollens were viable after 6 h. The stigma was receptive at the time of anthesis and continued for 24 h. The tree produces bright colour attractive flowers, which changed from yellow/light orange to scarlet/red from the inception of buds to wilting. The bright color of the flowers attracted floral visitors/pollinators thereby facilitated the pollination in this species. The observations of the floral biology and breeding system indicated the cross pollination behaviour, which limited the production of selfed seeds and would help to maintain the sustainable levels of heterozygosity among the various populations. Considerable amount of seeds produced in this species indicated that the species is capable of sustaining its progenies

  16. Intentional cargo disruption by nefarious means: Examining threats, systemic vulnerabilities and securitisation measures in complex global supply chains.

    Science.gov (United States)

    McGreevy, Conor; Harrop, Wayne

    2015-01-01

    Global trade and commerce requires products to be securely contained and transferred in a timely way across great distances and between national boundaries. Throughout the process, cargo and containers are stored, handled and checked by a range of authorities and authorised agents. Intermodal transportation involves the use of container ships, planes, railway systems, land bridges, road networks and barges. This paper examines the the nefarious nature of intentional disruption and nefarious risks associated with the movement of cargo and container freight. The paper explores main threats, vulnerabilities and security measures relevant to significant intermodal transit risk issues such as theft, piracy, terrorism, contamination, counterfeiting and product tampering. Three risk and vulnerability models are examined and basic standards and regulations that are relevant to safe and secure transit of container goods across international supply networks are outlined.

  17. Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction.

    Science.gov (United States)

    Blum, Kenneth; Thanos, Peter K; Oscar-Berman, Marlene; Febo, Marcelo; Baron, David; Badgaiyan, Rajendra D; Gardner, Eliot; Demetrovics, Zsolt; Fahlke, Claudia; Haberstick, Brett C; Dushaj, Kristina; Gold, Mark S

    Recently there has been debate concerning the role of brain dopamine in reward and addiction. David Nutt and associates eloquently proposed that dopamine (DA) may be central to psycho stimulant dependence and some what important for alcohol, but not important for opiates, nicotine or even cannabis. Others have also argued that surfeit theories can explain for example cocaine seeking behavior as well as non-substance-related addictive behaviors. It seems prudent to distinguish between what constitutes "surfeit" compared to" deficit" in terms of short-term (acute) and long-term (chronic) brain reward circuitry responsivity. In an attempt to resolve controversy regarding the contributions of mesolimbic DA systems to reward, we review the three main competing explanatory categories: "liking", "learning", and "wanting". They are (a) the hedonic impact -liking reward, (b) the ability to predict rewarding effects-learning and (c) the incentive salience of reward-related stimuli -wanting. In terms of acute effects, most of the evidence seems to favor the "surfeit theory". Due to preferential dopamine release at mesolimbic-VTA-caudate-accumbens loci most drugs of abuse and Reward Deficiency Syndrome (RDS) behaviors have been linked to heightened feelings of well-being and hyperdopaminergic states.The "dopamine hypotheses" originally thought to be simple, is now believed to be quite complex and involves encoding the set point of hedonic tone, encoding attention, reward expectancy, and incentive motivation. Importantly, Willuhn et al. shows that in a self-administration paradigm, (chronic) excessive use of cocaine is caused by decreased phasic dopamine signaling in the striatum. In terms of chronic addictions, others have shown a blunted responsivity at brain reward sites with food, nicotine, and even gambling behavior. Finally, we are cognizant of the differences in dopaminergic function as addiction progresses and argue that relapse may be tied to dopamine deficiency

  18. Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours.

    Science.gov (United States)

    Tombeau Cost, K; Unternaehrer, E; Plamondon, A; Steiner, M; Meaney, M; Atkinson, L; Kennedy, J L; Fleming, A S

    2017-02-01

    Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post-partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision-making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch-A-Sketch co-operation task. Mediation analyses showed that OXTR rs2254298 A-carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision-making task (estimate = 0.115, P Dopamine SNPs were not associated with any measure of executive function or parenting (all P > 0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post-partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  19. Homeostatic mechanisms in dopamine synthesis and release: a mathematical model

    Directory of Open Access Journals (Sweden)

    Nijhout H Frederik

    2009-09-01

    Full Text Available Abstract Background Dopamine is a catecholamine that is used as a neurotransmitter both in the periphery and in the central nervous system. Dysfunction in various dopaminergic systems is known to be associated with various disorders, including schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore, microdialysis studies have shown that addictive drugs increase extracellular dopamine and brain imaging has shown a correlation between euphoria and psycho-stimulant-induced increases in extracellular dopamine 1. These consequences of dopamine dysfunction indicate the importance of maintaining dopamine functionality through homeostatic mechanisms that have been attributed to the delicate balance between synthesis, storage, release, metabolism, and reuptake. Methods We construct a mathematical model of dopamine synthesis, release, and reuptake and use it to study homeostasis in single dopaminergic neuron terminals. We investigate the substrate inhibition of tyrosine hydroxylase by tyrosine, the consequences of the rapid uptake of extracellular dopamine by the dopamine transporters, and the effects of the autoreceoptors on dopaminergic function. The main focus is to understand the regulation and control of synthesis and release and to explicate and interpret experimental findings. Results We show that the substrate inhibition of tyrosine hydroxylase by tyrosine stabilizes cytosolic and vesicular dopamine against changes in tyrosine availability due to meals. We find that the autoreceptors dampen the fluctuations in extracellular dopamine caused by changes in tyrosine hydroxylase expression and changes in the rate of firing. We show that short bursts of action potentials create significant dopamine signals against the background of tonic firing. We explain the observed time courses of extracellular dopamine responses to stimulation in wild type mice and mice that have genetically altered dopamine transporter densities and the observed

  20. Vulnerability and behavioral response to ultraviolet radiation in the components of a foliar mite prey-predator system

    Science.gov (United States)

    Tachi, Fuyuki; Osakabe, Masahiro

    2012-12-01

    Ambient ultraviolet-B (UVB) radiation impacts plant-dwelling arthropods including herbivorous and predatory mites. However, the effects of UVB on prey-predator systems, such as that between the herbivorous spider mite and predatory phytoseiid mite, are poorly understood. A comparative study was conducted to determine the vulnerability and behavioral responses of these mites to ultraviolet (UV) radiation. First, we analyzed dose-response (cumulative irradiance-mortality) curves for the eggs of phytoseiid mites ( Neoseiulus californicus, Neoseiulus womersleyi, and Phytoseiulus persimilis) and the spider mite ( Tetranychus urticae) to UVB radiation from a UV lamp. This indicated that the phytoseiid mites were more vulnerable than the spider mite, although P. persimilis was slightly more tolerant than the other two phytoseiid mites. Second, we compared the avoidance behavior of adult female N. californicus and two spider mite species ( T. urticae, a lower leaf surface user; Panonychus citri, an upper leaf surface user) in response to solar UV and visible light. N. californicus actively avoided both types of radiation, whereas P. citri showed only minimal avoidance behavior. T. urticae actively avoided UV as well as N. californicus but exhibited a slow response to visible light as well as P. citri. Such variation in vulnerability and avoidance behavior accounts for differences in the species adaptations to solar UVB radiation. This may be the primary factor determining habitat use among these mites on host plant leaves, subsequently affecting accessibility by predators and also intraguild competition.

  1. Impact of performance interdependencies on structural vulnerability: A systems perspective of storm surge risk to coastal residential communities

    International Nuclear Information System (INIS)

    Hatzikyriakou, Adam; Lin, Ning

    2017-01-01

    Interaction between residential structures during natural hazards can lead to interdependencies in their performance. During storm surge, for example, structures can affect the performance of inland buildings by generating damaging waterborne debris or by beneficially dampening surge loads. Quantifying the impact of this interaction on structural vulnerability is critical for risk assessment and informed decision-making. In this study we present and implement two general modeling approaches for investigating such interdependencies. The first method is to condition the vulnerability of a structure on the performance of neighboring buildings using a Markov model. The second uses a marginal model to account for correlation between damage observations when estimating a structure's vulnerability to the hazard. Both approaches are implemented using a case study of an impacted coastal community during Hurricane Sandy (2012). Findings indicate that a structure's performance during storm surge is strongly dependent on the damage state of the structure immediately seaward. Furthermore, considering the correlated damage states of buildings increases statistical uncertainty when relating structural performance to hazard intensity. Motivated by these findings, we propose a more coordinated approach to coastal risk mitigation which considers the effects of interdependencies on insurance pricing, structural design, mitigation strategies and community resilience. - Highlights: • Interaction between residential structures leads to performance interdependencies. • Interdependencies during storm surge are due to debris and structural shielding. • Markov model treats interdependencies as an additional demand parameter. • Marginal model incorporates damage correlation into regression estimation. • System behavior should be considered in community risk and resilience.

  2. Vulnerability Identification Errors in Security Risk Assessments

    OpenAIRE

    Taubenberger, Stefan

    2014-01-01

    At present, companies rely on information technology systems to achieve their business objectives, making them vulnerable to cybersecurity threats. Information security risk assessments help organisations to identify their risks and vulnerabilities. An accurate identification of risks and vulnerabilities is a challenge, because the input data is uncertain. So-called ’vulnerability identification errors‘ can occur if false positive vulnerabilities are identified, or if vulnerabilities remain u...

  3. Cross-hemispheric dopamine projections have functional significance

    Science.gov (United States)

    Fox, Megan E.; Mikhailova, Maria A.; Bass, Caroline E.; Takmakov, Pavel; Gainetdinov, Raul R.; Budygin, Evgeny A.; Wightman, R. Mark

    2016-01-01

    Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson’s disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine–lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres. PMID:27298371

  4. Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system

    DEFF Research Database (Denmark)

    Ádori, Csaba; Glück, Laura; Barde, Swapnali

    2015-01-01

    Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is n......Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites...... morphometry and mRNA profiling in a cohort of Alzheimer’s and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer’s disease, we found significantly....../IV and onwards, i.e., a process preceding advanced Alzheimer’s pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine β-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 −/− mice and...

  5. Redistributing vulnerabilities

    DEFF Research Database (Denmark)

    Seeberg, Jens; Padmawati, Retna Siwi

    2015-01-01

    It is widely accepted that the social distribution of vulnerability in a given society may turn hazardous events into disasters. This distributional approach draws attention to continuities that explain catastrophes by virtue of the workings of society prior to the event. In this paper, we draw...... attention to the social processes whereby vulnerability is modified and renegotiated during the post-disaster period where resources for disaster alleviation and reconstruction enter local communities. Specifically, we explore the social dynamics of house damage classification in the wake of the 2006...... Central Java earthquake, and we explore relations between citizens and the state during post-disaster house reconstruction. We argue that disastrous outcomes of catastrophic events do not follow pre-existing fault lines of vulnerability in a simple or predictable manner, and that the social process...

  6. Presence and function of dopamine transporter (DAT in stallion sperm: dopamine modulates sperm motility and acrosomal integrity.

    Directory of Open Access Journals (Sweden)

    Javier A Urra

    Full Text Available Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT, serotonin (SERT and norepinephrine (NET transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylaminostyryl]-N-methylpyridinium iodide (ASP(+, as substrate. In addition, we also showed that dopamine (1 mM treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909 and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility.

  7. α-Cyclodextrin dimer complexes of dopamine and levodopa derivatives to assess drug delivery to the central nervous system: ADME and molecular docking studies

    Science.gov (United States)

    Shityakov, Sergey; Broscheit, Jens; Förster, Carola

    2012-01-01

    This paper attempts to predict and emphasize molecular interactions of dopamine, levodopa, and their derivatives (Dopimid compounds) containing 2-phenyl-imidazopyridine moiety with the α-cyclodextrin dimer in order to assess and improve drug delivery to the central nervous system. The molecular docking method is used to determine the energetic profiles, hydrogen bond formation, and hydrophobic effect of 14 host–guest complexes. The results show that the “chemical branching” represented by additional ethyl-acetate residue is energetically unfavorable and promotes a conformational shift due to the high root mean square deviation levels. This phenomenon is characterized by a low number of H-bonds and a significant decrease of the host–guest hydrophobic potential surface. Finally, the overall docking procedure presents a powerful rationale for screening and analyzing various sets of promising drug-like chemical compounds in the fields of supramolecular chemistry, molecular sensing, synthetic receptors, and nanobiotechnology. PMID:22811606

  8. Migration in the Anthropocene: how collective navigation, environmental system and taxonomy shape the vulnerability of migratory species.

    Science.gov (United States)

    Hardesty-Moore, Molly; Deinet, Stefanie; Freeman, Robin; Titcomb, Georgia C; Dillon, Erin M; Stears, Keenan; Klope, Maggie; Bui, An; Orr, Devyn; Young, Hillary S; Miller-Ter Kuile, Ana; Hughey, Lacey F; McCauley, Douglas J

    2018-05-19

    Recent increases in human disturbance pose significant threats to migratory species using collective movement strategies. Key threats to migrants may differ depending on behavioural traits (e.g. collective navigation), taxonomy and the environmental system (i.e. freshwater, marine or terrestrial) associated with migration. We quantitatively assess how collective navigation, taxonomic membership and environmental system impact species' vulnerability by (i) evaluating population change in migratory and non-migratory bird, mammal and fish species using the Living Planet Database (LPD), (ii) analysing the role of collective navigation and environmental system on migrant extinction risk using International Union for Conservation of Nature (IUCN) classifications and (iii) compiling literature on geographical range change of migratory species. Likelihood of population decrease differed by taxonomic group: migratory birds were more likely to experience annual declines than non-migrants, while mammals displayed the opposite pattern. Within migratory species in IUCN, we observed that collective navigation and environmental system were important predictors of extinction risk for fishes and birds, but not for mammals, which had overall higher extinction risk than other taxa. We found high phylogenetic relatedness among collectively navigating species, which could have obscured its importance in determining extinction risk. Overall, outputs from these analyses can help guide strategic interventions to conserve the most vulnerable migrations.This article is part of the theme issue 'Collective movement ecology'. © 2018 The Author(s).

  9. Determination of the Environmental Vulnerability into Potiguar Basin , on Macau (RN region, using Geographical Information System

    Directory of Open Access Journals (Sweden)

    Raquel Franco de Souza Lima

    2006-08-01

    Full Text Available The coastal zones are important regions by their fragilities and dynamic. The research area is placed near Macau (RN county and it is known by land petrol exploration. About this view, this research had made maps of the natural and environmental vulnerability from base maps of geology, soils, vegetation, geomorphology and of using and occupation. Analyzing these maps it can diagnostic sensible areas from environmental problems, by allowing recommendation toward best advantage from control and protect activities. The vulnerability map elaboration aims to show the intensity and its distribution, mainly considering the stability related to morphogenesis and pedogenesis. The methodology procedures consists in the logical integration of different available data, and the set of all these information were integrated to make and to store a georeferencing data base into the Arcview ® GIS 3.2 software, permitting a systematic analysis of each element of thematic maps. The maps crossing was based on stability concept of each unit by considering the ecodynamic analysis concept.

  10. Weather hazards and vulnerabilities for the European transport system - a risk panorama. EWENT project D5.1

    Energy Technology Data Exchange (ETDEWEB)

    Molarius, R.; Leviakangas, P.; Ronty, J.; Oiva, K. (eds.)

    2012-09-15

    This deliverable of EWENT project estimates the risks of extreme weather on European transport system. The main object of work package 5 in EWENT project was to perform a risk analysis based on impact and probability assessments carried out in earlier work packages (WP2-WP3). The results of WP 5 can be used as a starting point when deciding on the risk reduction measures, strategies and policies in the European Union. This deliverable also serves as a background material for the synthesis report (named shortly as Risk Panorama), which will summarise the findings of risk assessment and previous work packages. The methodological approach of EWENT is based on the generic risk management standard (IEC 60300-3-9) and starts with the identification of hazardous extreme weather phenomena, followed by an impact assessment and concluded by mitigation and risk control measures. This report pools the information from EWENT's earlier work packages, such as risk identification and estimation, into a 'risk panorama' and provides a holistic picture on the risks of extreme weather in different parts of Europe and EU transport network. The risk assessment is based on the definition of transport systems' vulnerability to extreme weather events in different countries and on calculations of the most probable causal chains, starting from adverse weather phenomena and ending up with events that pose harmful consequences to the transport systems in different climate regions. The latter part, the probabilistic section, is the hazard analysis. The vulnerability of a particular mode in a particular country is a function of exposure (indicated by transport or freight volumes and population density), susceptibility (infrastructure quality index, indicating overall resilience) and coping capacity (measured by GDP per capita). Hence, we define the extreme weather risk as Risk = hazard times vulnerability = P(negative consequences) times V[f(exposure, susceptibility, coping

  11. Assessing vulnerability

    NARCIS (Netherlands)

    Hellmuth, M.; Kabat, P.

    2003-01-01

    It is in the shantytowns and rural villages of the Third World that floods and droughts strike hardest and deepest. Vulnerability to the vagaries of climate depends not only on location, but, crucially, on the capacity of the victims to cope with the impacts of extreme weather. So, where are the

  12. Vulnerability of steam generator super-emergency feeding. Super-emergency feedwater system for the Mochovce NPP steam-generators

    International Nuclear Information System (INIS)

    Hlasova, M.; Jary, A.

    1997-01-01

    The following major requirements and criteria fulfillment concerned the super-emergency feedwater system (SEFW) system were proposed: to provide sufficient water amount for accident conditions, inclusive seismicity, even during required SEFW system operation for the time period of 72 hours; to analyse ensuring of residual heat removal in case of a station black-out; to state criteria for water supply by the SEFW system into the steam generators (SGs); to simplify the existing connection scheme inclusive decreasing the number of valves, which are in series; to analyse and provide the system protection against a common cause failure, which the SEFW system did not provide in some parts (possibilities of three systems failure due to flooding; vulnerability of all tanks by the operation building fall in case of a seismic event; vulnerability of all tanks due to extreme climatic conditions; vulnerability of all tanks during new seismic loading and consequent mutual endangering; the possibility of three systems failure due to common routing in the vicinity of high; energy media on the +14,7 m floor in the intermediate machinery building and due to inconsistent electrical valves secured power supply systems); to analyse temperature increase impact on the number of uses and lifetime of SGs; to perform a change of SEFW system pipelines routing layout outside the dangerous area of the +14,7 m floor in the intermediate machinery building with high energy media; checking the thanks autonomy. There were performed analyses of selected transient operation modes. The analyses had the following objectives: necessary flowrate of the SEFW in case of the primary side stabilised temperature of 140 C till 72 hours of the process duration; sufficient capacity of one subsystem for the supply of sufficient water amount; sufficient water reserve in the tanks at given conditions; and other. Accident situations were evaluated using an analysis and three characteristic operation modes were

  13. Development methodologies evaluation of the charge and vulnerability of the Aquifer Guarani System in Argentina and Uruguay

    International Nuclear Information System (INIS)

    Rodriguez, L.; Gomez, A.; Oleaga, A.

    2007-01-01

    The study area is located in the Uruguayan/Brazilian border near the cities of Rivera (Uruguay) and Santa Ana do Livramento (Brasil) and their surroundings. The area is characterized by the presence of fractured basalts of the Arapey or Serra Geral Formation and sandstones of the Tacuarembo-Rivera (Botucatu) Formation that form up the Guarani Aquifer System (GAS). The general objectives of the project were to adapt and apply methodologies to estimate the recharge to the fractured aquifer and to estimate the fraction of that recharge that eventually reaches the GAS in the study area. The development of new methodologies for the vulnerability assessment of the Serra Geral Formation was also sought. Piezo metric data, geological and structural analyses and hydrogeochemical studies were used to construct the conceptual model of the system behavior. Then, a numerical model was implemented to validate the conceptual model, reproduce the current system behavior, and estimate the recharge to the sandstones (either from the overlying basalts or from rainfall). The model would indicate a downward flow, i.e., recharge from the fractured basalt to the shallow aquifer, and from it to the deep aquifer, which matches the hypothesis of this research. As for the vulnerability of the GAS below the fractured zone, and reminding that there would be recharge from the basalt, adapted methodologies from flat-land scenarios were proposed, integrating the degree of fracturing of the volcanic rocks and the thickness of the unsaturated zone

  14. The Tile-map Based Vulnerability Assessment Code of a Physical Protection System: SAPE (Systematic Analysis of Protection Effectiveness)

    International Nuclear Information System (INIS)

    Jang, Sung Soon; Kwak, Sung Woo; Yoo, Ho Sik; Kim, Jung Soo; Yoon, Wan Ki

    2008-01-01

    Increasing threats on nuclear facilities demands stronger physical protection system (PPS) within the limited budget. For this reason we need an efficient physical protection system and before making an efficient PPS we need to evaluate it. This evaluation process should faithfully reflect real situation, reveal weak points and unnecessary protection elements, and give comparable quantitative values. Performance based analysis helps to build an efficient physical protection system. Instead of regulating the number of sensors and barriers, the performance based analysis evaluates a PPS fit to the situation of a facility. The analysis assesses delay (sensors) and detection (barriers) of a PPS against an intrusion, and judges whether a response force arrives before intruders complete their job. Performance based analysis needs complicated calculation and, hence, several assessment codes have been developed. A code called the estimation of adversary sequence interruption (EASI) was developed to analyze vulnerability along a single intrusion path. The systematic analysis of vulnerability to intrusion (SAVI) code investigates multi-paths to a valuable asset in an actual facility. SAVI uses adversary sequence diagram to describe multi-paths

  15. Can Organic Farming Reduce Vulnerabilities and Enhance the Resilience of the European Food System? A Critical Assessment Using System Dynamics Structural Thinking Tools

    Directory of Open Access Journals (Sweden)

    Natalia Brzezina

    2016-09-01

    Full Text Available In a world of growing complexity and uncertainty, food systems must be resilient, i.e., able to deliver sustainable and equitable food and nutrition security in the face of multiple shocks and stresses. The resilience of the European food system that relies mostly on conventional agriculture is a matter of genuine concern and a new approach is called for. Does then organic farming have the potential to reduce vulnerabilities and improve the resilience of the European food system to shocks and stresses? In this paper, we use system dynamics structural thinking tools to identify the vulnerabilities of the conventional food system that result from both its internal structure as well as its exposure to external disturbances. Further, we evaluate whether organic farming can reduce the vulnerabilities. We argue here that organic farming has some potential to bring resilience to the European food system, but it has to be carefully designed and implemented to overcome the contradictions between the dominant socio-economic organization of food production and the ability to enact all organic farming’s principles—health, ecology, fairness and care—on a broader scale.

  16. Between the River and the City. Resilience VS Vulnerability in Settlement Systems of Fluvial Environment

    Directory of Open Access Journals (Sweden)

    Filippo Angelucci

    2014-05-01

    Full Text Available In the presence of increasingly frequent extreme weather phenomena, water management in complex settlement areas, such as those located in a fluvial environment, involves not only the reduction of that area’s fragility but, more importantly, the regeneration of the lost interactions between the physical, economic and social dimensions of the area. Research conducted along the Pescara river has taken up this challenge, reinterpreting the critical environmental situation of the case study areas as the chance to oversee a more ample “water project” which could tackle the vulnerability of the territory by identifying new means of resilience and responsiveness to adverse natural events and by carrying out proactive coexistence scenarios between cities, inhabitants, institutions and natural resources.

  17. Dopamine hypothesis of mania

    OpenAIRE

    Cookson, John

    2014-01-01

    s­of­the­Speakers­/­Konuşmacı­leriThe discovery of dopamine and its pathwaysDopamine (DA) was first synthesized in 1910 from 3,4-dihydroxy phenyl alanine (DOPA) by Barger and Ewens at Wellcome Laboratories in London. It is a cathecholamine and in the 1940s Blaschko in Cambridge proposed that DA was a precursor in synthesis of the cat-echolamine neurotransmitters noradrenaline (norepinephrine) and adrenaline (epinephrine). In 1957 it was shown to be present in the brain with other catecholamin...

  18. Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism.

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

    BACKGROUND: For the normal resolution of an acute inflammatory response, neutrophil (PMN) apoptosis is essential to maintain immune homeostasis and to limit inappropriate host tissue damage. A delay in PMN apoptosis has been implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS). Dopamine, a biogenic amine with known cardiovascular and neurotransmitter properties, is used in patients with SIRS to maintain hemodynamic stability. We sought to determine whether dopamine may also have immunoregulatory properties capable of influencing PMN apoptosis, function, and activation state in patients with SIRS. METHODS: PMNs were isolated from healthy volunteers and patients with SIRS and treated with varying doses of dopamine and a dopamine D-1 receptor agonist, fenoldopam. PMN apoptosis was assessed every 6 hours with use of propidium iodide DNA staining and PMN function was assessed with use of respiratory burst activity, phagocytosis ability, and CD11a, CD11b, and CD18 receptor expression as functional markers. RESULTS: There was a significant delay in PMN apotosis in patients with SIRS compared with controls. Treatment of isolated PMNs from both healthy controls and patients with SIRS with 10 and 100 mumol\\/L dopamine induced apoptosis. PMN ingestive and cytocidal capacity were both decreased in patients with SIRS compared with controls. Treatment with dopamine significantly increased phagocytic function. Fenoldopam did not induce PMN apoptosis. CONCLUSION: Our data demonstrate for the first time that dopamine induces PMN apoptosis and modulates PMN function both in healthy controls and in patients with SIRS. These results indicate that dopamine may be beneficial during SIRS through a nonhemodynamic PMN-dependent proapoptotic mechanism.

  19. Extreme climatic events: reducing ecological and social systems vulnerabilities; Evenements climatiques extremes: reduire les vulnerabilites des systemes ecologiques et sociaux

    Energy Technology Data Exchange (ETDEWEB)

    Decamps, H.; Amatore, C.; Bach, J.F.; Baccelli, F.; Balian, R.; Carpentier, A.; Charnay, P.; Cuzin, F.; Davier, M.; Dercourt, J.; Dumas, C.; Encrenaz, P.; Jeannerod, M.; Kahane, J.P.; Meunier, B.; Rebut, P.H.; Salencon, J.; Spitz, E.; Suquet, P.; Taquet, P.; Valleron, A.J.; Yoccoz, J.C.; Chapron, J.Y.; Fanon, J.; Andre, J.C.; Auger, P.; Bourrelier, P.H.; Combes, C.; Derrida, B.; Laubier, L.; Laval, K.; Le Maho, Y.; Marsily, G. De; Petit, M.; Schmidt-Laine, C.; Birot, Y.; Peyron, J.L.; Seguin, B.; Barles, S.; Besancenot, J.P.; Michel-Kerjan, E.; Hallegatte, S.; Dumas, P.; Ancey, V.; Requier-Desjardins, M.; Ducharnes, A.; Ciais, P.; Peylin, P.; Kaniewski, D.; Van Campo, E.; Planton, S.; Manuguerra, J.C.; Le Bars, Y.; Lagadec, P.; Kessler, D.; Pontikis, C.; Nussbaum, R.

    2010-07-01

    The Earth has to face more and more devastating extreme events. Between 1970 and 2009, at the worldwide scale, the 25 most costly catastrophes all took place after 1987, and for more than half of them after 2001. Among these 25 catastrophes, 23 were linked to climate conditions. France was not spared: the December 1999 storms led to 88 deaths, deprived 3.5 million households of electricity and costed more than 9 billion euros. The 2003 heat wave led to about 15000 supernumerary deaths between August 1 and August 20. The recent Xynthia storm, with its flood barrier ruptures, provoked 53 deaths in addition to many other tragedies that took place in areas liable to flooding. In the present day context of climate change, we know that we must be prepared to even more dangerous events, sometimes unexpected before. These events can have amplified effects because of the urban development, the overpopulation of coastal areas and the anthropization of natural environments. They represent real 'poverty traps' for the poorest countries of the Earth. The anticipation need is real but is our country ready to answer it? Does it have a sufficient contribution to international actions aiming at reducing risks? Is his scientific information suitable? France is not less vulnerable than other countries. It must reinforce its prevention, its response and resilience capacities in the framework of integrated policies of catastrophes risk management as well as in the framework of climate change adaptation plans. This reinforcement supposes the development of vigilance systems with a better risk coverage and benefiting by the advances gained in the meteorology and health domains. It supposes a town and country planning allowing to improve the viability of ecological and social systems - in particular by protecting their diversity. Finally, this reinforcement requires inciting financial coverage solutions for catastrophes prevention and for their management once they have taken

  20. Vulnerability and Hydrogeologic Risk of the Guarani Aquifer System in the outcropping area located in Rivera Uruguay

    International Nuclear Information System (INIS)

    Montano, J.; Collazo, P.; Auge, M.

    2004-01-01

    The Project named Vulnerability and Hydrogeologic Risk of the Guarani Aquifer System in the outcropping area located in Rivera, Uruguay is developed by the Faculty of Science University of the Republic, together with the Faculty of Natural and Exact Sciences of the University of Buenos Aires, and it is financed by the Guarani Fund of Universities - Project for the Environmental Protection and Sustainable Development of the Guarani Aquifer System. This project has the aim of researching the characteristics and the hydrogeologic behavior of the Guarani Aquifer in the North portion of Uruguay, Department of Rivera (outcropping area). Moreover, to propose measures directed to their preservation through their sustainable use. The Hydrogeologic Study of the Guarani Aquifer System in this area will contribute not only with the best knowledge in its dynamics, but also helping to take measures in the water management and to avoid potential risks of contamination [es

  1. Reduced connectivity and inter-hemispheric symmetry of the sensory system in a rat model of vulnerability to developing depression.

    Science.gov (United States)

    Ben-Shimol, E; Gass, N; Vollmayr, B; Sartorius, A; Goelman, G

    2015-12-03

    Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full LH behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

    Science.gov (United States)

    Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

    2013-01-01

    Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

  3. Access to HIV community services by vulnerable populations: evidence from an enhanced HIV/AIDS surveillance system.

    Science.gov (United States)

    Madden, H C E; Phillips-Howard, P A; Hargreaves, S C; Downing, J; Bellis, M A; Vivancos, R; Morley, C; Syed, Q; Cook, P A

    2011-05-01

    HIV disproportionately affects vulnerable populations such as black and minority ethnic groups, men who have sex with men (MSM) and migrants, in many countries including those in the UK. Community organisations in the UK are charitable non-governmental organisations with a proportion of the workforce who volunteer, and provide invaluable additional support for people living with HIV (PLWHIV). Information on their contribution to HIV care in vulnerable groups is relatively sparse. Data generated from an enhanced HIV surveillance system in North West England, UK, was utilised for this study. We aimed to determine the characteristics of individuals who chose to access community services in addition to clinical services (1375 out of 4195 records of PLWHIV in clinical services). Demographic information, risk factors including residency status, uniquely gathered in this region, and deprivation scores were examined. Multivariate logistic regression modelling was conducted to predict the relative effect of patient characteristics on attendance at community services. Attendance at community services was highest in those living in the most, compared with least, deprived areas (p<0.001), and was most evident in MSM and heterosexuals. Compared to white UK nationals attendance was significantly higher in non-UK nationals of uncertain residency status (Adjusted odds ratio [AOR] = 21.91, 95% confidence interval [CI] 10.48-45.83; p<0.001), refugees (AOR = 5.75, 95% CI 3.3-10.03; p<0.001), migrant workers (AOR = 5.48, 95% CI 2.22-13.51; p<0.001) and temporary visitors (AOR = 3.44, 95% CI 1.68-7.05; p<0.001). Community services, initially established predominantly to support MSM, have responded to the changing demography of HIV and reach the most vulnerable members of society. Consequent to their support of migrant populations, community services are vital for the management of HIV in black and minority groups. Paradoxically, this coincides with increasing funding pressures on these

  4. Vulnerable Hunter

    OpenAIRE

    Md.Asha Begum; Y.VishnuPriya; V.ManoranjanBabu; ,O.Srinivasu

    2016-01-01

    This project "VULNERABLE HUNTER" application main aim is to detect risk in our mobile applications. This application contains modules like Fetch Application, Generate Score, Uninstall and Display Graph. Through this application it detects risk so that this application is very useful to smart phone users Now-a-days so many people are using smart phones and people are crazy about new apps. But by installing all the applications into our mobile may reduce its performance. Some apps c...

  5. Illicit dopamine transients: reconciling actions of abused drugs.

    Science.gov (United States)

    Covey, Dan P; Roitman, Mitchell F; Garris, Paul A

    2014-04-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. Although compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyperactivating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyperactivation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural rewards and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

    Science.gov (United States)

    Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

    2014-01-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

  7. Dopamine and anorexia nervosa.

    Science.gov (United States)

    Södersten, P; Bergh, C; Leon, M; Zandian, M

    2016-01-01

    We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are activated in anorexia nervosa, but it is not clear whether this response is due to the disorder or to its resulting nutritional deficit. When the body senses the shortage of nutrients, it rapidly shifts behavior toward foraging for food as a normal physiological response and the mesolimbic dopamine neurons may be involved in that process. On the other hand, the altered dopamine status of anorexics has been suggested to result from a brain abnormality that underlies their complex emotional disorder. We suggest that the outcomes of the treatments that emerge from that perspective remain poor because they target the mental symptoms that are actually the consequences of the food deprivation that accompanies anorexia. On the other hand, a method that normalizes the disordered eating behavior of anorexics results in much better physiological, behavioral, and emotional outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly render...

  9. Layered reward signalling through octopamine and dopamine in Drosophila.

    Science.gov (United States)

    Burke, Christopher J; Huetteroth, Wolf; Owald, David; Perisse, Emmanuel; Krashes, Michael J; Das, Gaurav; Gohl, Daryl; Silies, Marion; Certel, Sarah; Waddell, Scott

    2012-12-20

    Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

  10. Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

    Science.gov (United States)

    Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

    2016-05-01

    Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

  11. Early adverse experience and substance addiction: dopamine, oxytocin, and glucocorticoid pathways

    Science.gov (United States)

    Kim, Sohye; Kwok, Stephanie; Mayes, Linda C.; Potenza, Marc N.; Rutherford, Helena J. V.; Strathearn, Lane

    2016-01-01

    Substance addiction may follow a chronic, relapsing course and critically undermine the physical and psychological well-being of the affected individual and the social units of which the individual is a member. Despite the public health burden associated with substance addiction, treatment options remain suboptimal, with relapses often seen. The present review synthesizes growing insights from animal and human research to shed light upon developmental and neurobiological pathways that may increase susceptibility to addiction. We examine the dopamine system, the oxytocin system, and the glucocorticoid system, as they are particularly relevant to substance addiction. Our aim is to delineate how early adverse experience may induce long-lasting alterations in each of these systems at molecular, neuroendocrine, and behavioral levels and ultimately lead to heightened vulnerability to substance addiction. We further discuss how substance addiction in adulthood may increase the risk of suboptimal caregiving for the next generation, perpetuating the intergenerational cycle of early adverse experiences and addiction. PMID:27508337

  12. Vulnerability of deep groundwater in the Bengal Aquifer System to contamination by arsenic

    Science.gov (United States)

    Burgess, W.G.; Hoque, M.A.; Michael, H.A.; Voss, C.I.; Breit, G.N.; Ahmed, K.M.

    2010-01-01

    Shallow groundwater, the primary water source in the Bengal Basin, contains up to 100 times the World Health Organization (WHO) drinking-water guideline of 10g l 1 arsenic (As), threatening the health of 70 million people. Groundwater from a depth greater than 150m, which almost uniformly meets the WHO guideline, has become the preferred alternative source. The vulnerability of deep wells to contamination by As is governed by the geometry of induced groundwater flow paths and the geochemical conditions encountered between the shallow and deep regions of the aquifer. Stratification of flow separates deep groundwater from shallow sources of As in some areas. Oxidized sediments also protect deep groundwater through the ability of ferric oxyhydroxides to adsorb As. Basin-scale groundwater flow modelling suggests that, over large regions, deep hand-pumped wells for domestic supply may be secure against As invasion for hundreds of years. By contrast, widespread deep irrigation pumping might effectively eliminate deep groundwater as an As-free resource within decades. Finer-scale models, incorporating spatial heterogeneity, are needed to investigate the security of deep municipal abstraction at specific urban locations. ?? 2010 Macmillan Publishers Limited. All rights reserved.

  13. Identification of protective actions to reduce the vulnerability of safety-critical systems to malevolent acts: A sensitivity-based decision-making approach

    International Nuclear Information System (INIS)

    Wang, Tai-Ran; Pedroni, Nicola; Zio, Enrico

    2016-01-01

    A classification model based on the Majority Rule Sorting method has been previously proposed by the authors to evaluate the vulnerability of safety-critical systems (e.g., nuclear power plants) with respect to malevolent intentional acts. In this paper, we consider a classification model previously proposed by the authors based on the Majority Rule Sorting method to evaluate the vulnerability of safety-critical systems (e.g., nuclear power plants) with respect to malevolent intentional acts. The model is here used as the basis for solving an inverse classification problem aimed at determining a set of protective actions to reduce the level of vulnerability of the safety-critical system under consideration. To guide the choice of the set of protective actions, sensitivity indicators are originally introduced as measures of the variation in the vulnerability class that a safety-critical system is expected to undergo after the application of a given set of protective actions. These indicators form the basis of an algorithm to rank different combinations of actions according to their effectiveness in reducing the safety-critical systems vulnerability. Results obtained using these indicators are presented with regard to the application of: (i) one identified action at a time, (ii) all identified actions at the same time or (iii) a random combination of identified actions. The results are presented with reference to a fictitious example considering nuclear power plants as the safety-critical systems object of the analysis. - Highlights: • We use a hierarchical framework to represent the vulnerability. • We use an empirical classification model to evaluate vulnerability. • Sensitivity indicators are introduced to rank protective actions. • Constraints (e.g., budget limitations) are accounted for. • Method is applied to fictitious Nuclear Power Plants.

  14. Dopamine, T cells and multiple sclerosis (MS).

    Science.gov (United States)

    Levite, Mia; Marino, Franca; Cosentino, Marco

    2017-05-01

    Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in

  15. The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors.

    Science.gov (United States)

    Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F

    2016-02-01

    Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release.

  16. Functional characterization of dopamine transporter in vivo using Drosophila melanogaster behavioral analysis.

    Directory of Open Access Journals (Sweden)

    Taro eUeno

    2014-09-01

    Full Text Available Dopamine mediates diverse functions such as motivation, reward, attention, learning/memory and sleep/arousal. Recent studies using model organisms including the fruit fly, have elucidated various physiological functions of dopamine, and identified specific neural circuits for these functions. Flies with mutations in the Drosophila dopamine transporter (dDAT gene show enhanced dopamine signaling, and short sleep and memory impairment phenotypes. However, understanding the mechanism by which dopamine signaling causes these phenotypes requires an understanding of the dynamics of dopamine release. Here we report the effects of dDAT expression on behavioral traits. We show that dDAT expression in a subset of dopaminergic neurons is sufficient for normal sleep. dDAT expression in other cell types such as Kenyon cells and glial cells can also rescue the short sleep phenotype of dDAT mutants. dDAT mutants also show a down-regulation of the D1-like dopamine receptor dDA1, and this phenotype is rescued when dDAT is expressed in the same cell types in which it rescues sleep. On the other hand, dDAT overexpression in mushroom bodies, which are the target of memory forming dopamine neurons, abolishes olfactory aversive memory. Our data demonstrate that expression of extrasynaptic dopamine transporters can rescue some aspects of dopamine signaling in dopamine transporter mutants. These results provide novel insights into regulatory systems that modulate dopamine signaling.

  17. Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

    Science.gov (United States)

    2015-01-01

    In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

  18. Firing properties of dopamine neurons in freely moving dopamine-deficient mice: Effects of dopamine receptor activation and anesthesia

    OpenAIRE

    Robinson, Siobhan; Smith, David M.; Mizumori, Sheri J. Y.; Palmiter, Richard D.

    2004-01-01

    To examine the regulation of midbrain dopamine neurons, recordings were obtained from single neurons of freely moving, genetically engineered dopamine-deficient (DD) mice. DD mice were tested without dopamine signaling (basal state) and with endogenous dopamine signaling (after L-dopa administration). In the basal state, when dopamine concentration in DD mice is

  19. Groundwater vulnerability map for South Africa

    African Journals Online (AJOL)

    Chiedza Musekiwa

    Coastal vulnerability is the degree to which a coastal system is susceptible to, ... methods, indicator-based approaches, GIS-based decision support systems and ..... E 2005, 'Coastal Vulnerability and Risk Parameters', European Water, vol.

  20. Open Source Vulnerability Database Project

    Directory of Open Access Journals (Sweden)

    Jake Kouns

    2008-06-01

    Full Text Available This article introduces the Open Source Vulnerability Database (OSVDB project which manages a global collection of computer security vulnerabilities, available for free use by the information security community. This collection contains information on known security weaknesses in operating systems, software products, protocols, hardware devices, and other infrastructure elements of information technology. The OSVDB project is intended to be the centralized global open source vulnerability collection on the Internet.

  1. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  2. NEW DOPAMINE AGONISTS IN CARDIOVASCULAR THERAPY

    NARCIS (Netherlands)

    GIRBES, ARJ; VANVELDHUISEN, DJ; SMIT, AJ

    1992-01-01

    Dopamine, a naturally occurring catecholamine, has been extensively used in intensive care for many years. Dopamine stimulates different types of adrenergic receptors: alpha-1 and -2, beta-1 and -2, and dopamine-1 and -2. The renal effects of dopamine are the result of dopamine-1 receptor (DA1)

  3. A Framework For Analyzing And Mitigating The Vulnerabilities Of Complex Systems Via Attack And Protection Trees

    National Research Council Canada - National Science Library

    Edge, Kenneth S

    2007-01-01

    .... Attack trees by themselves do not provide enough decision support to system defenders. This research develops the concept of using protection trees to offer a detailed risk analysis of a system...

  4. Vulnerability of remote keyless-entry systems against pulsed electromagnetic interference and possible improvements

    NARCIS (Netherlands)

    van de Beek, G.S.; Leferink, Frank Bernardus Johannes

    2016-01-01

    Remote keyless-entry systems are systems that are widely used to control access to vehicles or buildings. The system is increasingly secured against hacking attacks by use of encryption and code algorithms. However, there are effective hacker attacks that rely on jamming the wireless link from the

  5. Cyber Vulnerabilities Within Critical Infrastructure: The Flaws of Industrial Control Systems in the Oil and Gas Industry

    Science.gov (United States)

    Alpi, Danielle Marie

    The 16 sectors of critical infrastructure in the US are susceptible to cyber-attacks. Potential attacks come from internal and external threats. These attacks target the industrial control systems (ICS) of companies within critical infrastructure. Weakness in the energy sector's ICS, specifically the oil and gas industry, can result in economic and ecological disaster. The purpose of this study was to establish means for oil companies to identify and stop cyber-attacks specifically APT threats. This research reviewed current cyber vulnerabilities and ways in which a cyber-attack may be deterred. This research found that there are insecure devices within ICS that are not regularly updated. Therefore, security issues have amassed. Safety procedures and training thereof are often neglected. Jurisdiction is unclear in regard to critical infrastructure. The recommendations this research offers are further examination of information sharing methods, development of analytic platforms, and better methods for the implementation of defense-in-depth security measures.

  6. Dopamine Agonists and Pathologic Behaviors

    Directory of Open Access Journals (Sweden)

    Brendan J. Kelley

    2012-01-01

    Full Text Available The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson’s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.

  7. Detecting C Program Vulnerabilities

    OpenAIRE

    Anton, Ermakov; Natalia, Kushik

    2011-01-01

    C/C++ language is widely used for developing tools in various applications, in particular, software tools for critical systems are often written in C language. Therefore, the security of such software should be thoroughly tested, i.e., the absence of vulnerabilities has to be confirmed. When detecting C program vulnerabilities static source code analysis can be used. In this paper, we present a short survey of existing software tools for such analysis and show that for some kinds of C code vu...

  8. Potential Safety Benefit of the Blind Spot Detection System for Large Trucks on the Vulnerable Road Users in Taiwan

    Directory of Open Access Journals (Sweden)

    Wang Ming-Hang

    2016-01-01

    Full Text Available Considering motorcyclists, pedestrians and bicyclists as vulnerable road users (VRUs, more than 75 percent of the victims of fatal crashes involving large trucks in Taiwan are VRUs. Most crashes occurred at or were due to the blind spots of large trucks because of the size and traveling locations of the VRUs. This study applies typology and statistical methods to estimate the potential safety benefit of blind spot detection (BSD systems for large trucks on VRUs. The pre-crash scenarios associated with the blind spots of large trucks were derived by counting the maneuvers of large trucks and VRUs, prior to crashes, the truck drivers’ improper behaviors (cause of crashes, and the crash types. The number of crashes and fatalities were counted for the pre-crash scenario relevant to the BSD systems. A value of 0.8 of human machine interface factor (HMIF based on a previous study was applied to estimate the potential safety benefits of the BSD system. The results show that the implementation of BSD systems on all large trucks could help avoid about 24, 10, and 11 percent of large truck-involved crashes with pedestrians, bicycles, and motorcycles, respectively. The BSD systems could also save 5 pedestrians, 3 bicyclists, and 15 motorcyclists per year from crashes involving large trucks.

  9. Growth of dopamine crystals

    Energy Technology Data Exchange (ETDEWEB)

    Patil, Vidya, E-mail: vidya.patil@ruparel.edu; Patki, Mugdha, E-mail: mugdha.patki@ruparel.edu [D. G. Ruparel College, Senapati Bapat Marg, Mahim, Mumbai – 400 016 (India)

    2016-05-06

    Many nonlinear optical (NLO) crystals have been identified as potential candidates in optical and electro-optical devices. Use of NLO organic crystals is expected in photonic applications. Hence organic nonlinear optical materials have been intensely investigated due to their potentially high nonlinearities, and rapid response in electro-optic effect compared to inorganic NLO materials. There are many methods to grow organic crystals such as vapor growth method, melt growth method and solution growth method. Out of these methods, solution growth method is useful in providing constraint free crystal. Single crystals of Dopamine have been grown by evaporating the solvents from aqueous solution. Crystals obtained were of the size of orders of mm. The crystal structure of dopamine was determined using XRD technique. Images of crystals were obtained using FEG SEM Quanta Series under high vacuum and low KV.

  10. Dopamine and dopamine receptor D1 associated with decreased social interaction.

    Science.gov (United States)

    Liu, Qiang; Shi, Jieyun; Lin, Rongfei; Wen, Tieqiao

    2017-05-01

    Deficits in social interaction are hallmarks of neurological and psychiatric disorders. However, its underlying mechanism is still unclear. Here, we show that the loss of dendritic cell factor 1 (Dcf1) in the nervous system of mice induces social interaction deficiency, autism-like behaviour, and influences social interaction via the dopamine system. Dopamine receptor D1 agonist rescues this social cognition phenotype, and improves short-term plasticity. Together, this study presents a new genetic mechanism that affects social interaction and may provide a new way to improve positive social interaction and treat autism spectrum disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Soft error evaluation and vulnerability analysis in Xilinx Zynq-7010 system-on chip

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xuecheng; He, Chaohui; Liu, Shuhuan, E-mail: liushuhuan@mail.xjtu.edu.cn; Zhang, Yao; Li, Yonghong; Xiong, Ceng; Tan, Pengkang

    2016-09-21

    Radiation-induced soft errors are an increasingly important threat to the reliability of modern electronic systems. In order to evaluate system-on chip's reliability and soft error, the fault tree analysis method was used in this work. The system fault tree was constructed based on Xilinx Zynq-7010 All Programmable SoC. Moreover, the soft error rates of different components in Zynq-7010 SoC were tested by americium-241 alpha radiation source. Furthermore, some parameters that used to evaluate the system's reliability and safety were calculated using Isograph Reliability Workbench 11.0, such as failure rate, unavailability and mean time to failure (MTTF). According to fault tree analysis for system-on chip, the critical blocks and system reliability were evaluated through the qualitative and quantitative analysis.

  12. Comparison between a dual-head and a brain-dedicated SPECT system in the measurement of the loss of dopamine transporters with [123I]FP-CIT

    International Nuclear Information System (INIS)

    Varrone, Andrea; Sansone, Valeria; Pappata, Sabina; Salvatore, Marco; Pellecchia, Maria T.; Salvatore, Elena; de Michele, Giuseppe; Filla, Alessandro; Barone, Paolo; Amboni, Marianna

    2008-01-01

    Dual-head SPECT systems are used by many clinical departments for [ 123 I]FP-CIT SPECT imaging, while triple-head or brain-dedicated systems with better imaging performance are more commonly used by research institutions. There are limited data comparing the capability of the two types of system to measure dopamine transporter (DAT) loss in vivo. The aim of this study was to compare the ability of a dual-head and a brain-dedicated SPECT system to estimate the degree of DAT loss in different movement disorders with variable nigrostriatal impairment, with [ 123 I]FP-CIT. Four patients with essential tremor, 24 with Parkinson's disease (PD), six with spinocerebellar ataxia type 2 and six controls were studied with [ 123 I]FP-CIT. SPECT scans were performed on a dual-head (E.CAM - Siemens) and subsequently on a brain-dedicated system (Ceraspect - DSI). Striatal DAT outcome measures on the E.CAM and the Ceraspect were strongly correlated and the putamen-to-caudate ratios were almost identical. Although the measured values were lower by 52 ± 25% in caudate and by 51 ± 31% in putamen on the E.CAM (p < 0.0001), the average striatal DAT decrease in each patient group compared with controls was similar for both systems. In PD patients, similar correlations (p < 0.05) were found between motor UPDRS or Hoehn and Yahr stage and striatal DAT density. Despite underestimation of striatal DAT outcome measures, the E.CAM showed similar capability as the Ceraspect in measuring the degree of nigrostriatal dopaminergic deficit and assessing the correlation between DAT outcome measures and clinical variables of PD severity and stage. (orig.)

  13. VISA-2 - a general, vulnerability-oriented method for evaluating the performance of integrated safeguards/security systems at nuclear facilities

    International Nuclear Information System (INIS)

    Harris, L.; Owel, W.R.

    1981-01-01

    This paper discusses the VISA (Vulnerability of Integrated Safeguards Analysis) method, developed in 1976-77 for the Nuclear Regulatory Commission, and which has been adapted more recently to a broader range of uses. The performance of VISA systems is evaluated in terms of how they perform as an integrated safeguards/security system. The resulting method has been designated VISA-2. 7 refs

  14. Lightning vulnerability of nuclear explosive test systems at the Nevada Test Site

    International Nuclear Information System (INIS)

    Hasbrouck, R.T.

    1985-01-01

    A task force chartered to evaluate the effects of lightning on nuclear explosives at the Nevada Test Site has made several recommendations intended to provide lightning-invulnerable test device systems. When these recommendations have been implemented, the systems will be tested using full-threat-level simulated lightning

  15. THE POLITICAL SYSTEM IN THE REPUBLIC OF MOLDOVA: EVOLUTIONS, VULNERABILITIES AND OPPORTUNITIES FOR MODERNIZATION

    Directory of Open Access Journals (Sweden)

    MÎNDRU VALERIU

    2016-12-01

    Full Text Available The article analyzed the evolution of the political system in Moldova. The authors note three stages of the formation and consolidation of the political system in the country which have directly infl uenced the political domain and democratization of the society. The analysis is based on the legislative experience of other countries and the opinions of experts.

  16. Transforming vulnerability.

    Science.gov (United States)

    Jones, Patricia S; Zhang, Xinwei Esther; Meleis, Afaf I

    2003-11-01

    Asian American immigrant women engaged in filial caregiving are at special risk for health problems due to complex contextual factors related to immigration, cultural traditions, and role transition. This study examines the experience of two groups of immigrant Asian American women who are caring for older parents. A total of 41 women (22 Chinese American and 19 Filipino American) were interviewed in a study based on Strauss and Corbin's grounded theory methodology. The women were determined to be loyal to their traditional culture, which included strong filial values, while adapting to a new culture. Through the struggle of meeting role expectations and coping with paradox, the women mobilized personal and family resources to transform vulnerability into strength and well-being.

  17. Southern African Coastal vulnerability assessment

    CSIR Research Space (South Africa)

    Rautenbach, C

    2015-10-01

    Full Text Available or business. The CSIR coastal systems group uses specialist skills in coastal engineering, geographic engineering systems and numerical modelling to assess and map vulnerable coastal ecosystems to develop specific adaptation measures and coastal protection...

  18. The dopamine theory of addiction: 40 years of highs and lows.

    Science.gov (United States)

    Nutt, David J; Lingford-Hughes, Anne; Erritzoe, David; Stokes, Paul R A

    2015-05-01

    For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.

  19. The Index of Vulnerability: An anthropological method linking social-ecological systems to mental and physical health outcomes.

    Science.gov (United States)

    Tallman, Paula Skye

    2016-08-01

    Researchers need measures of vulnerability that are grounded in explicit theoretical and conceptual frameworks, that are sensitive to local contexts, and that are easy to collect. This paper presents the Index of Vulnerability (IoV), a quantitative yet anthropologically-informed method connecting social-ecological systems to mental and physical health outcomes. The IoV combines measures of five life domains; food insecurity, water insecurity, access to healthcare, social support, and social status. Scores on this index increase for each life domain where the individual falls into a "high risk" category. Thus, individuals with the highest IoV scores are those who are at risk across multiple life domains. This approach makes the IoV malleable to local contexts, as scholars can choose which measure of each life domain is most appropriate for their study population. An anthropological study conducted among 225 Awajún adults living in the Peruvian Amazon from March to November of 2013 showed that men with higher IoV scores had significantly lower summary fat skinfolds, lower triglyceride levels, and a greater probability of reporting moderate to severe somatic symptoms and poor perceived health. Awajún women with higher IoV scores had significantly elevated perceived stress levels and a greater probability of reporting poor perceived health and moderate to severe somatic and depressive symptoms. Importantly, comparing the IoV to its constituent parts shows that it predicts a wider range of mental and physical health outcomes than any of the life domains alone. The IoV is presented here in relation to the broader political-economic and cultural context of the Awajún, forwarding a critical biocultural approach within anthropology, and demonstrating the IoV's utility for other scholars and practitioners. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The Behavioral Approach System (BAS) Model of Vulnerability to Bipolar Disorder: Evidence of a Continuum in BAS Sensitivity across Adolescence.

    Science.gov (United States)

    Liu, Richard T; Burke, Taylor A; Abramson, Lyn Y; Alloy, Lauren B

    2017-11-04

    Behavioral Approach System (BAS) sensitivity has been implicated in the development of a variety of different psychiatric disorders. Prominent among these in the empirical literature are bipolar spectrum disorders (BSDs). Given that adolescence represents a critical developmental stage of risk for the onset of BSDs, it is important to clarify the latent structure of BAS sensitivity in this period of development. A statistical approach especially well-suited for delineating the latent structure of BAS sensitivity is taxometric analysis, which is designed to evaluate whether the latent structure of a construct is taxonic (i.e., categorical) or dimensional (i.e., continuous) in nature. The current study applied three mathematically non-redundant taxometric procedures (i.e., MAMBAC, MAXEIG, and L-Mode) to a large community sample of adolescents (n = 12,494) who completed two separate measures of BAS sensitivity: the BIS/BAS Scales Carver and White (Journal of Personality and Social Psychology, 67, 319-333. 1994) and the Sensitivity to Reward and Sensitivity to Punishment Questionnaire (Torrubia et al. Personality and Individual Differences, 31, 837-862. 2001). Given the significant developmental changes in reward sensitivity that occur across adolescence, the current investigation aimed to provide a fine-grained evaluation of the data by performing taxometric analyses at an age-by-age level (14-19 years; n for each age ≥ 883). Results derived from taxometric procedures, across all ages tested, were highly consistent, providing strong evidence that BAS sensitivity is best conceptualized as dimensional in nature. Thus, the findings suggest that BAS-related vulnerability to BSDs exists along a continuum of severity, with no natural cut-point qualitatively differentiating high- and low-risk adolescents. Clinical and research implications for the assessment of BSD-related vulnerability are discussed.

  1. A Framework For Analyzing And Mitigating The Vulnerabilities Of Complex Systems Via Attack And Protection Trees

    National Research Council Canada - National Science Library

    Edge, Kenneth S

    2007-01-01

    .... In addition to developing protection trees, this research improves the existing concept of attack trees and develops rule sets for the manipulation of metrics used in the security of complex systems...

  2. An Approach to Vulnerability Assessment for Navy Supervisory Control and Data Acquisition (SCADA) Systems

    National Research Council Canada - National Science Library

    Hart, Dennis

    2004-01-01

    .... SCADA systems are relied upon in a large number of the sectors that make up the critical infrastructure, and their importance was reinforced during the massive power outage that occurred in August 2003...

  3. Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson's disease

    International Nuclear Information System (INIS)

    Swanson, Randel L.; Newberg, Andrew B.; Acton, Paul D.; Siderowf, Andrew; Wintering, Nancy; Alavi, Abass; Mozley, P. David; Plossl, Karl; Udeshi, Michelle; Hurtig, Howard

    2005-01-01

    Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [ 99m Tc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders. Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [ 99m Tc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Student's ttests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures. Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p 99m Tc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases. (orig.)

  4. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems.

    Science.gov (United States)

    Li, Xiang; Huang, Mengbing; Yang, Lihua; Guo, Ningning; Yang, Xiaoyan; Zhang, Zhimin; Bai, Ming; Ge, Lu; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

    2018-01-01

    Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABA B R were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABA B R in the VTA and NAc.

  5. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2018-05-01

    Full Text Available Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1 is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA and γ-aminobutyric acid (GABA systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA and nucleus accumbens (NAc in wild-type (WT mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc.

  6. Impacts of climate change on the municipal water management system in the Kingdom of Bahrain: Vulnerability assessment and adaptation options

    Directory of Open Access Journals (Sweden)

    Waleed K. Al-Zubari

    Full Text Available An assessment of the vulnerability of the municipal water management system to the impacts of climate change in the Kingdom of Bahrain, manifested by the increase in demands due to increase in temperatures, is conducted using a dynamic mathematical model representing the water sector in the kingdom. The model is developed using WEAP software and was calibrated and validated by historical matching utilizing data for the period 2000–2012. The model is used in the evaluation of the municipal water sector performance in terms of municipal water demands and their associated cost without and with climate change impacts scenarios for the period 2012–2030. The impact of climate change on the municipal water system is quantified as the difference between the two scenarios in three selected cost indicators: financial (production, conveyance and distribution costs, economic (natural gas asset consumption by desalination plants, and environmental (CO2 emissions by desalination plants. The vulnerability assessment indicated that the current municipal water management system in Bahrain is generally inefficient and associated with relatively high costs, which are expected to increase with time under the current policies and management approach focusing on supply-side management. The increase in temperature will increase these already high costs, and would exacerbate the water management challenges in Bahrain. However, these mounting challenges also present an opportune moment for Bahrain to review its current water resources management approaches and practices and to integrate climate change adaptation measures into its water planning and policies. In order to build an adaptive management capacity of the municipal water management system in Bahrain, a number of management interventions are proposed and evaluated, individually and combined, for their effectiveness in enhancing the efficiency of the management system using the developed dynamic model. These

  7. Energy vulnerability relationships

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, B.R.; Boesen, J.L.

    1998-02-01

    The US consumption of crude oil resources has been a steadily growing indicator of the vitality and strength of the US economy. At the same time import diversity has also been a rapidly developing dimension of the import picture. In the early 1970`s, embargoes of crude oil from Organization of Producing and Exporting Countries (OPEC) created economic and political havoc due to a significant lack of diversity and a unique set of economic, political and domestic regulatory circumstances. The continued rise of imports has again led to concerns over the security of our crude oil resource but threats to this system must be considered in light of the diversity and current setting of imported oil. This report develops several important issues concerning vulnerability to the disruption of oil imports: (1) The Middle East is not the major supplier of oil to the United States, (2) The US is not vulnerable to having its entire import stream disrupted, (3) Even in stable countries, there exist vulnerabilities to disruption of the export stream of oil, (4) Vulnerability reduction requires a focus on international solutions, and (5) DOE program and policy development must reflect the requirements of the diverse supply. Does this increasing proportion of imported oil create a {open_quotes}dependence{close_quotes}? Does this increasing proportion of imported oil present a vulnerability to {open_quotes}price shocks{close_quotes} and the tremendous dislocations experienced during the 1970`s? Finally, what is the vulnerability of supply disruptions from the current sources of imported oil? If oil is considered to be a finite, rapidly depleting resource, then the answers to these questions must be {open_quotes}yes.{close_quotes} However, if the supply of oil is expanding, and not limited, then dependence is relative to regional supply sources.

  8. Dopamine modulates metabolic rate and temperature sensitivity in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Taro Ueno

    Full Text Available Homeothermal animals, such as mammals, maintain their body temperature by heat generation and heat dissipation, while poikilothermal animals, such as insects, accomplish it by relocating to an environment of their favored temperature. Catecholamines are known to regulate thermogenesis and metabolic rate in mammals, but their roles in other animals are poorly understood. The fruit fly, Drosophila melanogaster, has been used as a model system for the genetic studies of temperature preference behavior. Here, we demonstrate that metabolic rate and temperature sensitivity of some temperature sensitive behaviors are regulated by dopamine in Drosophila. Temperature-sensitive molecules like dTrpA1 and shi(ts induce temperature-dependent behavioral changes, and the temperature at which the changes are induced were lowered in the dopamine transporter-defective mutant, fumin. The mutant also displays a preference for lower temperatures. This thermophobic phenotype was rescued by the genetic recovery of the dopamine transporter in dopamine neurons. Flies fed with a dopamine biosynthesis inhibitor (3-iodo-L-tyrosine, which diminishes dopamine signaling, exhibited preference for a higher temperature. Furthermore, we found that the metabolic rate is up-regulated in the fumin mutant. Taken together, dopamine has functions in the temperature sensitivity of behavioral changes and metabolic rate regulation in Drosophila, as well as its previously reported functions in arousal/sleep regulation.

  9. Effective Decision Maker-Scientist Engagement:Climate Change Vulnerability Analysis of California's Water System to Using Decision Scaling.

    Science.gov (United States)

    Schwarz, A. M.; Ray, P.; Brown, C.; Wi, S.

    2016-12-01

    For nearly 2 years the California Department of Water Resources (CDWR) has been working with the University of Massachusetts Amherst (UMass) to evaluate climate change vulnerabilities to the California State Water Project. Working cooperatively, the team has developed tools and methods to employ a decision scaling approach to CDWR's existing water system model (CalSim-II/CalLite 3.0). This presentation will discuss how and why this partnership came to be, the co-production model the team has developed to share expertise, the new understanding of the system that has been gained through the process, and current and future efforts to influence planning and investments based on the findings of the work. This cooperative decision-maker-with-scientist engagement is unique in that CDWR has not outsourced the application of the science to their systems, and instead has worked directly with UMass researchers to develop the process, produce results, and interpret findings. Further, CDWR staff has worked with UMass researchers to present results in ways that are more useable and actionable for decision-makers. As will be shown, many of these graphics allow the team to use the science differently to improve decision making.

  10. A Framework For Analyzing And Mitigating The Vulnerabilities Of Complex Systems Via Attack And Protection Trees

    Science.gov (United States)

    2007-07-01

    Systems, Ciudad Real, Spain, 2002. [Ame00] "Metamorphosis," in American Heritage Dictionary of the English Language Fourth ed: Houghton Mifflin Company...Beyond Fear: Thinking Sensibly About Security in an Uncertain World. New York: Copernicus Books, 2003. [Sch99] Schneier, B. "Modeling Security

  11. Assessing command and control system vulnerabilities in underdeveloped, degraded and denied operational environments

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2013-06-01

    Full Text Available not always be clearly understood within the setting of a complex sociotechnical system. Humans may have the ability to develop work-around strategies to accomplish a task in the absence of some technical supports. Cognitive Work Analysis (CWA...

  12. A threat-vulnerability based risk analysis model for cyber physical system security

    CSIR Research Space (South Africa)

    Ledwaba, Lehlogonolo

    2017-01-01

    Full Text Available model. An analysis of the Natanz system shows that, with an actual case security-risk score at Mitigation level 5, the infested facilities barely avoided a situation worse than the one which occurred. The paper concludes with a discussion on the need...

  13. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Mizushima Jin

    2012-07-01

    Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  14. Sustainable management of agriculture activity on areas with soil vulnerability to compaction trough a developed decision support system (DSS)

    Science.gov (United States)

    Moretto, Johnny; Fantinato, Luciano; Rasera, Roberto

    2017-04-01

    One of the main environmental effects of agriculture is the negative impacts on areas with soil vulnerability to compaction and undersurface water derived from inputs and treatment distributions. A solution may represented from the "Precision Farming". Precision Farming refers to a management concept focusing on (near-real time) observation, measurement and responses to inter- and intra-variability in crops, fields and animals. Potential benefits may include increasing crop yields and animal performance, cost and labour reduction and optimisation of process inputs, all of which would increase profitability. At the same time, Precision Farming should increase work safety and reduce the environmental impacts of agriculture and farming practices, thus contributing to the sustainability of agricultural production. The concept has been made possible by the rapid development of ICT-based sensor technologies and procedures along with dedicated software that, in the case of arable farming, provides the link between spatially-distributed variables and appropriate farming practices such as tillage, seeding, fertilisation, herbicide and pesticide application, and harvesting. Much progress has been made in terms of technical solutions, but major steps are still required for the introduction of this approach over the common agricultural practices. There are currently a large number of sensors capable of collecting data for various applications (e.g. Index of vegetation vigor, soil moisture, Digital Elevation Models, meteorology, etc.). The resulting large volumes of data need to be standardised, processed and integrated using metadata analysis of spatial information, to generate useful input for decision-support systems. In this context, a user-friendly IT applications has been developed, for organizing and processing large volumes of data from different types of remote sensing and meteorological sensors, and for integrating these data into user-friendly farm management support

  15. Dopamine release dynamics change during adolescence and after voluntary alcohol intake.

    Directory of Open Access Journals (Sweden)

    Sara Palm

    Full Text Available Adolescence is associated with high impulsivity and risk taking, making adolescent individuals more inclined to use drugs. Early drug use is correlated to increased risk for substance use disorders later in life but the neurobiological basis is unclear. The brain undergoes extensive development during adolescence and disturbances at this time are hypothesized to contribute to increased vulnerability. The transition from controlled to compulsive drug use and addiction involve long-lasting changes in neural networks including a shift from the nucleus accumbens, mediating acute reinforcing effects, to recruitment of the dorsal striatum and habit formation. This study aimed to test the hypothesis of increased dopamine release after a pharmacological challenge in adolescent rats. Potassium-evoked dopamine release and uptake was investigated using chronoamperometric dopamine recordings in combination with a challenge by amphetamine in early and late adolescent rats and in adult rats. In addition, the consequences of voluntary alcohol intake during adolescence on these effects were investigated. The data show a gradual increase of evoked dopamine release with age, supporting previous studies suggesting that the pool of releasable dopamine increases with age. In contrast, a gradual decrease in evoked release with age was seen in response to amphetamine, supporting a proportionally larger storage pool of dopamine in younger animals. Dopamine measures after voluntary alcohol intake resulted in lower release amplitudes in response to potassium-chloride, indicating that alcohol affects the releasable pool of dopamine and this may have implications for vulnerability to addiction and other psychiatric diagnoses involving dopamine in the dorsal striatum.

  16. Clinical usefulness of dopamine transporter imaging

    International Nuclear Information System (INIS)

    Kim, Jong Min; Kim, Yu Kyeong; Kim, Sang Eun; Jeon, Beom S.

    2007-01-01

    Imaging of the dopamine transporter (DAT) provides a marker for the integrity of presynaptic nigrostriatal dopaminergic system. DAT density is reduced in Parkinson disease, multiple system atrophy, and progressive supranuclear palsy. In patients with suspicious parkinsonism, normal DAT imaging suggests an alternative diagnosis such as essential tremor, vascular parkinsonism, or drug-induced parkinsonism. DAT imaging is a useful tool to aid clinician's differential diagnosis in parkinsonism

  17. Application of systems analysis techniques to vulnerability studies of complex installations

    International Nuclear Information System (INIS)

    Bott, T.F.

    1986-01-01

    Application of reliability and risk analysis methods (particularly fault trees) to failure analysis of systems in hostile manmade environments is discussed. Methods for constructing, analyzing, and interpreting the fault trees, graphs, and diagrams are described. The application of fault-trees, directed graphs, and functional diagrams to problems in sabotage, survivability, and information protection is discussed in general terms. Special problems encountered in this type of analysis are discussed, and future research directions are considered

  18. Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction.

    Directory of Open Access Journals (Sweden)

    Stéphanie eOlière

    2013-09-01

    Full Text Available Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamine. Interestingly, recent accumulating evidence points toward the involvement of the endocannabinoid system (ECBS in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep-insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. The aims of this article are to: 1 review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and 2 evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoid in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

  19. Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors.

    Science.gov (United States)

    Lee, Yunjin; Kim, Hannah; Kim, Ji-Eun; Park, Jin-Young; Choi, Juli; Lee, Jung-Eun; Lee, Eun-Hwa; Han, Pyung-Lim

    2018-07-01

    The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

  20. Assessment of vulnerable older adults' physical function according to the Japanese Long-Term Care Insurance (LTCI) system and Fried's criteria for frailty syndrome.

    Science.gov (United States)

    Nemoto, Miyuki; Yabushita, Noriko; Kim, Mi-Ji; Matsuo, Tomoaki; Seino, Satoshi; Tanaka, Kiyoji

    2012-01-01

    This study aimed to evaluate the physical frailty status of vulnerable older adults as classified in the Japanese LTCI system and to compare this with Fried's definition. A total of 444 older adults were classified based on the LTCI system as independent, vulnerable, or dependent, and 400 of these participants also fit Fried's criteria for not frail, pre-frail or frail. We evaluated their physical function with a 12 item physical function test. We derived a physical function score (PFS) from these 12 items and a principal component analysis was used to make comparisons. The receiver operating characteristic (ROC) curve analysis was performed to identify the sensitivity and specificity of the PFS cut-off points to distinguish the dependent category from the other categories. We found significant differences and a hierarchical order for the PFSs among the three groups of the LTCI system (the independent, 0.41 ± 0.54; the vulnerable, -0.40 ± 0.76; and the dependent, -1.49 ± 0.73) and of Fried's definition (not frail, 0.50 ± 0.51; pre frail, -0.11 ± 0.63; and frail, -1.25 ± 0.98). The optimal cut-off value (OCV) was -0.593. This study showed that the range of physical function of people considered frail category (pre-frail, vulnerable, and frail) is wide and overlapping. That is, the physical function of vulnerable older adults is worse than the pre-frail, but better than the frail. To better recognize older adults in need of greater support, the vulnerable should also receive assessment of their frailty status according to Fried's definition. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Analysis of vulnerability to intrusion - a software for aid in training, design, and implementation of physical system

    International Nuclear Information System (INIS)

    Tangdan

    2002-01-01

    Full text: In this paper, we discuss briefly the developed level of physical protection system (PPS) in different Chinese history stage, and the relation between PPS and society, politics, military and security. It reveals the current status of application of PPS in China, and the level of design, implementation, evaluation and products. We also discuss the developing direction and applying tendency of PPS in future China. We mainly introduce a software using the ASD to evaluate the effectiveness of the PPS at a facility. It is used for training, design, and implementation of physical system. It identifies the path which adversaries can follow to accomplish sabotage or theft. For a specific PPS and threat, the most vulnerable path can be determined. The path probability of interruption P(I) establishes of the total PPS. Especially, we introduce how to specify threat characteristics bases the situation of present Chinese society, based global and local threat development. We also introduce how to build a data base of different elements based on the level of crime at present China. (author)

  2. THE VULNERABILITY OF THE BAIA MARE URBAN SYSTEM (ROMANIA TO EXTREME CLIMATE PHENOMENA DURING THE WARM SEMESTER OF THE YEAR

    Directory of Open Access Journals (Sweden)

    DRAGOTĂ CARMEN

    2013-03-01

    Full Text Available The geographical position of the Baia Mare Urban System (intra-hilly depression favours the occurrence of a wide range of extreme climate phenomena which, coupled with the industrial profile of the city (non-ferrous mining and metallurgical industry triggering typical emissions (CO2, SOX, particulate matters and Pb, might pose a significant threat to human health. The article is aiming to assess the occurrence, frequency and amplitude of these extreme climate phenomena based on monthly and daily extreme climatic values from Baia Mare weather station in order to identify the areas more exposed. A GIS-based qualitative-heuristic method was used, each extreme climatic hazard being evaluated on a 1 to 3 scale according to its significance/impact in the study area and assigned with a weight (w and a rank (r, resulting the climate hazard map for the warm semester of the year. The authors further relate the areas exposed to the selected extreme climatic events to socio-economic aspects: demographic and economic in order to delineate the spatial distribution of the environmental vulnerability in the Baia Mare Urban System.

  3. Network security vulnerabilities and personal privacy issues in Healthcare Information Systems: a case study in a private hospital in Turkey.

    Science.gov (United States)

    Namoğlu, Nihan; Ulgen, Yekta

    2013-01-01

    Healthcare industry has become widely dependent on information technology and internet as it moves from paper to electronic records. Healthcare Information System has to provide a high quality service to patients and a productive knowledge share between healthcare staff by means of patient data. With the internet being commonly used across hospitals, healthcare industry got its own share from cyber threats like other industries in the world. The challenge is allowing knowledge transfer to hospital staff while still ensuring compliance with security mandates. Working in collaboration with a private hospital in Turkey; this study aims to reveal the essential elements of a 21st century business continuity plan for hospitals while presenting the security vulnerabilities in the current hospital information systems and personal privacy auditing standards proposed by regulations and laws. We will survey the accreditation criteria in Turkey and counterparts in US and EU. We will also interview with medical staff in the hospital to understand the needs for personal privacy and the technical staff to perceive the technical requirements in terms of network security configuration and deployment. As hospitals are adopting electronic transactions, it should be considered a must to protect these electronic health records in terms of personal privacy aspects.

  4. A Dopamine Hypothesis of Autism Spectrum Disorder.

    Science.gov (United States)

    Pavăl, Denis

    2017-01-01

    Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis. © 2017 S. Karger AG, Basel.

  5. Applicability of vulnerability maps

    International Nuclear Information System (INIS)

    Andersen, L.J.; Gosk, E.

    1989-01-01

    A number of aspects to vulnerability maps are discussed: the vulnerability concept, mapping purposes, possible users, and applicability of vulnerability maps. Problems associated with general-type vulnerability mapping, including large-scale maps, universal pollutant, and universal pollution scenario are also discussed. An alternative approach to vulnerability assessment - specific vulnerability mapping for limited areas, specific pollutant, and predefined pollution scenario - is suggested. A simplification of the vulnerability concept is proposed in order to make vulnerability mapping more objective and by this means more comparable. An extension of the vulnerability concept to the rest of the hydrogeological cycle (lakes, rivers, and the sea) is proposed. Some recommendations regarding future activities are given

  6. Systemic Vulnerabilities to Suicide among Veterans from the Iraq and Afghanistan Conflicts: Review of Case Reports from a National Veterans Affairs Database

    Science.gov (United States)

    Mills, Peter D.; Huber, Samuel J.; Watts, Bradley Vince; Bagian, James P.

    2011-01-01

    While suicide among recently returned veterans is of great concern, it is a relatively rare occurrence within individual hospitals and clinics. Root cause analysis (RCA) generates a detailed case report that can be used to identify system-based vulnerabilities following an adverse event. Review of a national database of RCA reports may identify…

  7. A vulnerability-centric requirements engineering framework : Analyzing security attacks, countermeasures, and requirements based on vulnerabilities

    NARCIS (Netherlands)

    Elahi, G.; Yu, E.; Zannone, N.

    2010-01-01

    Many security breaches occur because of exploitation of vulnerabilities within the system. Vulnerabilities are weaknesses in the requirements, design, and implementation, which attackers exploit to compromise the system. This paper proposes a methodological framework for security requirements

  8. Integrated Vulnerability and Impacts Assessment for Natural and Engineered Water-Energy Systems in the Southwest and Southern Rocky Mountain Region

    Energy Technology Data Exchange (ETDEWEB)

    Tidwell, Vincent C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wolfsberg, Andrew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Macknick, Jordan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Middleton, Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-01-01

    In the Southwest and Southern Rocky Mountains (SWSRM), energy production, energy resource extraction, and other high volume uses depend on water supply from systems that are highly vulnerable to extreme, coupled hydro-ecosystem-climate events including prolonged drought, flooding, degrading snow cover, forest die off, and wildfire. These vulnerabilities, which increase under climate change, present a challenge for energy and resource planners in the region with the highest population growth rate in the nation. Currently, analytical tools are designed to address individual aspects of these regional energy and water vulnerabilities. Further, these tools are not linked, severely limiting the effectiveness of each individual tool. Linking established tools, which have varying degrees of spatial and temporal resolution as well as modeling objectives, and developing next-generation capabilities where needed would provide a unique and replicable platform for regional analyses of climate-water-ecosystem-energy interactions, while leveraging prior investments and current expertise (both within DOE and across other Federal agencies).

  9. Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

    Directory of Open Access Journals (Sweden)

    Rothmond Debora A

    2012-02-01

    Full Text Available Abstract Background Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5, catechol-O-methyltransferase, and monoamine oxidase (A and B in the developing human DLPFC (6 weeks -50 years. Results Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p O-methyltransferase (p = 0.024 were significantly higher in neonates and infants as was catechol-O-methyltransferase protein (32 kDa, p = 0.027. In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002 and dopamine D1 receptor protein expression increased throughout development (p Conclusions We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.

  10. Credit Risk Determinants in the Vulnerable Economies of Europe: Evidence from the Spanish Banking System

    Directory of Open Access Journals (Sweden)

    Gila-Gourgoura, E.

    2017-03-01

    Full Text Available Purpose: The purpose of this paper is to investigate the determinants of non-performing loans in the Spanish banking system over the period 1997Q4–2015Q3. This timeframe includes not only the booming period for the Spanish economy but also an extended post-crises interval which is missing from other studies for Spain. Design/methodology/approach: Using quarterly data from the Central Bank of Spain and from the European Central Bank, the paper employs the ARDL approach to cointegration to identify the existence of a long or short-run relationship between NPLs and a set of macroeconomic, bank-related and country-specific indicators. Findings: Findings from the ARDL model indicate that macroeconomic, bank-specific variables and interest rates are important determinants of non-performing loans in the Spanish banking system. Specifically, the real GDP, the Spanish long-term government bond yield, the return on equity, the total credit granted by the Spanish banks and their capital to assets ratio, explain credit risk in Spain both in the short and the long run. Research limitations/implications: Data on the bank-specific variables are for the whole banking industry, and not for individual banks. If such data were available, a comparison of the credit risk determinants between small/ big banks, private/public or domestic/foreign could be possibly made. Originality/value: These findings provide useful evidence to bank managers and policymakers in dealing with loans' defaults in Spain and in undertaking crucial reforms to stabilize the economy.

  11. Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine-serotonin systems in the prefrontal cortex of juvenile female rats.

    Science.gov (United States)

    Castro, Beatriz; Sánchez, Pilar; Torres, Jesús M; Ortega, Esperanza

    2015-10-01

    Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist. We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats. Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed. BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis. Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The roles of serine protease, intracellular and extracellular phenoloxidase in activation of prophenoloxidase system, and characterization of phenoloxidase from shrimp haemocytes induced by lipopolysaccharide or dopamine

    Science.gov (United States)

    Xie, Peng; Pan, Luqing; Xu, Wujie; Yue, Feng

    2013-09-01

    We investigated the effects of lipopolysaccharide (LPS) and dopamine (DA) on the activation of the prophenoloxidase (proPO) system of Litopenaeus vannamei. LPS and DA were shown with a negative dose-dependent effect on hyalne cells (HC), semi-granular cells (SGC), large granular cells (LGC), and total haemocyte count (THC). When haemocytes were treated with LPS or DA, serine proteinase activity and intracellular phenoloxidase (PO) activity were significantly reduced, but extracellular PO activity increased significantly. These findings indicated that the reduction in haemocyte counts was mainly because of the degranulation and activation of the proPO system from semi-granule and large granule cells. The PKC inhibitor, chelerythrine, and the TPK inhibitor, genistein, had an inhibitory effect on extracellular PO activity, while serine proteinase and intracellular PO activity increased. This suggests that the LPS and DA induce the activation of proPO in haemocytes via PKC and TPK-related signaling pathways, but serine proteinase may be activated only by PKC, as the genistein effects were not statistically significant. Electrophoresis analysis revealed that POs induced by LPS or DA have the same molecular mass and high diphenolase activity. Two PO bands at 526 kDa and 272 kDa were observed in PAGE, while in the haemocyte lysate supernatant (HLS), only a 272-kDa band was observed. This band was resolved after SDS-PAGE under non-reducing and reducing conditions into two groups of POs, 166 kDa and 126 kDa, and 78.1 kDa and 73.6 kDa, respectively, suggesting that PO in L. vannamei is an oligomer, which may have different compositions intra- and extracellularly.

  13. Vulnerability assessment of water resources - Translating a theoretical concept to an operational framework using systems thinking approach in a changing climate: Case study in Ogallala Aquifer

    Science.gov (United States)

    Anandhi, Aavudai; Kannan, Narayanan

    2018-02-01

    Water is an essential natural resource. Among many stressors, altered climate is exerting pressure on water resource systems, increasing its demand and creating a need for vulnerability assessments. The overall objective of this study was to develop a novel tool that can translate a theoretical concept (vulnerability of water resources (VWR)) to an operational framework mainly under altered temperature and precipitation, as well as for population change (smaller extent). The developed tool had three stages and utilized a novel systems thinking approach. Stage-1: Translating theoretical concept to characteristics identified from studies; Stage-2: Operationalizing characteristics to methodology in VWR; Stage-3: Utilizing the methodology for development of a conceptual modeling tool for VWR: WR-VISTA (Water Resource Vulnerability assessment conceptual model using Indicators selected by System's Thinking Approach). The specific novelties were: 1) The important characteristics in VWR were identified in Stage-1 (target system, system components, scale, level of detail, data source, frameworks, and indicator); 2) WR-VISTA combined two vulnerability assessments frameworks: the European's Driver-Pressure-State-Impact-Response framework (DPSIR) and the Intergovernmental Panel on Climate Change's framework (IPCC's); and 3) used systems thinking approaches in VWR for indicator selection. The developed application was demonstrated in Kansas (overlying the High Plains region/Ogallala Aquifer, considered the "breadbasket of the world"), using 26 indicators with intermediate level of detail. Our results indicate that the western part of the state is vulnerable from agricultural water use and the eastern part from urban water use. The developed tool can be easily replicated to other regions within and outside the US.

  14. Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux

    DEFF Research Database (Denmark)

    Binda, Francesca; Dipace, Concetta; Bowton, Erica

    2008-01-01

    of the dopamine (DA) transporter (DAT) as the site of direct interaction with SYN1A. Amphetamine (AMPH) increases the association of SYN1A with human DAT (hDAT) in a heterologous expression system (hDAT cells) and with native DAT in murine striatal synaptosomes. Immunoprecipitation of DAT from the biotinylated...

  15. Cyber attacks against state estimation in power systems: Vulnerability analysis and protection strategies

    Science.gov (United States)

    Liu, Xuan

    Power grid is one of the most critical infrastructures in a nation and could suffer a variety of cyber attacks. With the development of Smart Grid, false data injection attack has recently attracted wide research interest. This thesis proposes a false data attack model with incomplete network information and develops optimal attack strategies for attacking load measurements and the real-time topology of a power grid. The impacts of false data on the economic and reliable operations of power systems are quantitatively analyzed in this thesis. To mitigate the risk of cyber attacks, a distributed protection strategies are also developed. It has been shown that an attacker can design false data to avoid being detected by the control center if the network information of a power grid is known to the attacker. In practice, however, it is very hard or even impossible for an attacker to obtain all network information of a power grid. In this thesis, we propose a local load redistribution attacking model based on incomplete network information and show that an attacker only needs to obtain the network information of the local attacking region to inject false data into smart meters in the local region without being detected by the state estimator. A heuristic algorithm is developed to determine a feasible attacking region by obtaining reduced network information. This thesis investigates the impacts of false data on the operations of power systems. It has been shown that false data can be designed by an attacker to: 1) mask the real-time topology of a power grid; 2) overload a transmission line; 3) disturb the line outage detection based on PMU data. To mitigate the risk of cyber attacks, this thesis proposes a new protection strategy, which intends to mitigate the damage effects of false data injection attacks by protecting a small set of critical measurements. To further reduce the computation complexity, a mixed integer linear programming approach is also proposed to

  16. Pyrethroid pesticide-induced alterations in dopamine transporter function

    International Nuclear Information System (INIS)

    Elwan, Mohamed A.; Richardson, Jason R.; Guillot, Thomas S.; Caudle, W. Michael; Miller, Gary W.

    2006-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal dopaminergic pathway. Several epidemiological studies have demonstrated an association between pesticide exposure and the incidence of PD. Studies from our laboratory and others have demonstrated that certain pesticides increase levels of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for dopaminergic neurotoxins. Here, we report that repeated exposure (3 injections over 2 weeks) of mice to two commonly used pyrethroid pesticides, deltamethrin (3 mg/kg) and permethrin (0.8 mg/kg), increases DAT-mediated dopamine uptake by 31 and 28%, respectively. Using cells stably expressing DAT, we determined that exposure (10 min) to deltamethrin and permethrin (1 nM-100 μM) had no effect on DAT-mediated dopamine uptake. Extending exposures to both pesticides for 30 min (10 μM) or 24 h (1, 5, and 10 μM) resulted in significant decrease in dopamine uptake. This reduction was not the result of competitive inhibition, loss of DAT protein, or cytotoxicity. However, there was an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 h. These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD

  17. The experience of nuclear objects of the national nuclear center of the republic of Kazakhstan vulnerability analysis conducting with the help of assess analytic system

    International Nuclear Information System (INIS)

    Bogomolov, D.V.; Kozlov, N.I.

    2002-01-01

    Full text: In the Republic of Kazakhstan there is a number of nuclear objects which are potentially attractive to terrorists and criminal groups. They are also nuclear objects of the National Nuclear Center of the Republic of Kazakhstan (NNC RK) where there are research nuclear reactors with highly enriched nuclear fuel and nuclear materials storage. Within the international collaboration in the field of non-proliferation between the Republic of Kazakhstan and the United States of America in the period of 1996-1998 scientists of the Institute of Atomic Energy (IAE) of the NNC RK together with colleagues from the USA had conducted the system of works concerning vulnerability analysis of three nuclear objects of the NNC RK (reactor complexes IGR, 'Baikal-1' and WWR-K). It also concerned working out the projects of physical protection systems of the mentioned above objects modernization based on the conducted vulnerability analysis. These works included: identification of potential outer and inner threat for nuclear objects of the NNC RK; conducting of the analysis of vulnerability and expected risk of prospective threats for nuclear objects of the NNC RK with the help of analytical program for conducting of ASSESS nuclear objects vulnerability diagnosis; expert estimation of the results received in the course of vulnerability analysis and working out of recommendations on modernization of the systems of NNC RK nuclear objects (reactor complexes IGR, 'Baikal-1' and VVR-K) physical protection; working out of conceptual projects of NNC RK nuclear objects physical protection systems modification. The key point of the work was the vulnerability analysis conducting which required detailed examination of the basic data that provide modeling of aims, routes of movement and evaluation of potential violators detection probability in the protected zones, buildings and reactor systems premises. Analytic programming system of vulnerability estimation and protection effectiveness

  18. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Science.gov (United States)

    Frank, Guido K. W.

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. PMID:25988121

  19. Could dopamine agonists aid in drug development for anorexia nervosa?

    Science.gov (United States)

    Frank, Guido K W

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  20. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Directory of Open Access Journals (Sweden)

    Guido eFrank

    2014-11-01

    Full Text Available Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  1. MODELING OF NATURAL VULNERABILITY TO EROSION THROUGH THE GEOGRAPHIC INFORMATION SYSTEMS IN MORRO DO CHAPÉU-BA

    Directory of Open Access Journals (Sweden)

    Jocimara Souza Britto Lobão

    2005-05-01

    Full Text Available The environment is always in permanent change keeping its proper dynamics with its own rhythms.However, when the people move themselves occupying specific locations, some transformations can take place, constituting threats for the environment and for the manhimself. These changes are related to the enviroment degradation, which has erosion as one of its most significant processes.To understand this dynamic, it is necessary to model the environment in a way that is possible to identify areas with different degrees of natural vulnerability to erosion and thus provide actions that relieve these impacts.The erosive processes are part of the lithosphere modeling system and have its intensity degree more stable or more intense according to the sum of several physical variables (lithology, leveling, landscape, rainfall and hydrography, biological variables (ecosystem- the type of the original and second growth vegetation and anthropogenic variables (the type of human occupation and mining activities.The impact of the rain on the soil has its effects reduced because of the vegetation and so the pedogenesis is benefited and the erosive processes minimized. On the other hand, if there is no vegetation or if this is insuficient, morphogenesis becomes more intense and theerosive processes enhanced.

  2. Dopamine Oxidation and Autophagy

    Directory of Open Access Journals (Sweden)

    Patricia Muñoz

    2012-01-01

    Full Text Available The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction, α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxic α-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i the formation of α-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii the formation of adducts with α- and β-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes.

  3. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  4. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C......]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  5. Environmental tests of a digital safety channel: An investigation of stress-related vulnerabilities of computer-based safety system

    International Nuclear Information System (INIS)

    Korsah, K.; Wilson, T.L.; Wood, R.; Tanaka, T.

    1997-01-01

    This article presents the results of environmental stress tests performed on an experimental digital safety channel (EDSC) assembled at the Oak Ridge National Laboratory as part of the Qualification of Advanced Instrumentation and Controls Systems Research program, which was sponsored by the US Nuclear Regulatory Commission. The program is expected to provide recommendations for environmental qualification of digital safety systems. The purpose of the study was to investigate potential vulnerabilities of distributed computer systems used in safety applications when subjected to environmental stressors. The EDSC assembled for the tests employs technologies and digital subsystems representative of those proposed for use in advanced light-water reactors or as retrofits in existing plants. Subsystems include computers, electrical and optical serial communication links, fiber-optic network links, analog-to-digital and digital-to-analog converters, and multiplexers. The EDSC was subjected to selected stressors that are a potential risk to digital equipment in a mild environment. The selected stressors were electromagnetic and radiofrequency interferences (EMI-RFI), temperature, humidity, and smoke exposure. The stressors were applied at levels of intensity considerably higher than the safety channel is likely to experience in a normal nuclear power plant environment. Ranges of stress were selected at a sufficiently high level to induce errors so that failure modes that are characteristic of the technologies employed could be identified. On the basis of the incidence of functional errors observed during testing, EMI-RFI, smoke exposure, and high temperature coupled with high relative humidity, in that order, were found to have the greatest impact of the stressors investigated. The most prevalent stressor-induced upsets, as well as the most severe, were found to occur during the EMI-RFI tests

  6. Advanced methods for the risk, vulnerability and resilience assessment of safety-critical engineering components, systems and infrastructures, in the presence of uncertainties

    International Nuclear Information System (INIS)

    Pedroni, Nicolas

    2016-01-01

    Safety-critical industrial installations (e.g., nuclear plants) and infrastructures (e.g., power transmission networks) are complex systems composed by a multitude and variety of heterogeneous 'elements', which are highly interconnected and mutually dependent. In addition, such systems are affected by large uncertainties in the characterization of the failure and recovery behavior of their components, interconnections and interactions. Such characteristics raise concerns with respect to the system risk, vulnerability and resilience properties, which have to be accurately and precisely assessed for decision making purposes. In general, this entails the following main steps: (1) representation of the system to capture its main features; (2) construction of a mathematical model of the system; (3) simulation of the behavior of the system under various uncertain conditions to evaluate the relevant risk, vulnerability and resilience metrics by propagating the uncertainties through the mathematical model; (4) decision making to (optimally) determine the set of protective actions to effectively reduce (resp., increase) the system risk and vulnerability (resp., resilience). New methods to address these issues have been developed in this dissertation. Specifically, the research works have been carried out along two main axes: (1) the study of approaches for uncertainty modeling and quantification; (2) the development of advanced computational methods for the efficient system modeling, simulation and analysis in the presence of uncertainties. (author)

  7. Comparison of a traditional with a new approach based on Graph Theory to vulnerability assessment to natural hazards: a study case on a socio-economic complex system

    Science.gov (United States)

    Arosio, Marcello; Martina, Mario L. V.

    2017-04-01

    The emergent behaviour of the contemporary complex, socio-technical and interconnected society makes the collective risk greater than the sum of the parts and this requires a holistic, systematic and integrated approach. Although there have been major improvements in recent years, there are still some limitation in term of a holistic approach that is able to include the emergent value hidden in the connections between exposed elements and the interactions between the different spheres of the multi-hazards, vulnerability, exposure and resilience. To deal with these challenges it is necessary to consider the connections between the exposed elements (e.g. populations, schools, hospital, etc.) and to quantify the relative importance of the elements and their interconnections (e.g. the need of injured people to go to hospital or children to school). In a system (e.g. road, hospital and ecological network, etc.), or in a System of System (e.g. socio-technical urban service), there are critical elements that, beyond the intrinsic vulnerability, can be characterized by greater or lower vulnerability because of their physical, geographical, cyber or logical connections. To this aim, we propose in this study a comparative analysis between traditional reductionist approach and a new holistic approach to vulnerability assessment to natural hazards. The analysis considers a study case of a socio-economic complex system through an innovative approach based on the properties of graph G=(N,L). A graph consists of two sets N (nodes) and L (links): the nodes represent the single exposed elements (physical, social, environmental, etc.) to a hazard, while the links (or connections) represent the interaction between the elements. The final goal is to illustrate an application of this innovative approach of integrated collective vulnerability assessment.

  8. Vulnerability Assessments in Ethical Hacking

    OpenAIRE

    Ashiqur Rahman ,; Md. SarwarAlam Rasel; Asaduzzaman Noman; Shakh Md. Alimuzjaman Alim

    2016-01-01

    Ethical hackers use the same methods and techniques to test and bypass a system's defenses as their less-principled counterparts, but rather than taking advantage of any vulnerabilities found, they document them and provide actionable advice on how to fix them so the organization can improve its overall security. The purpose of ethical hacking is to evaluate the security of a network or system's infrastructure. It entails finding and attempting to exploit any vulnerabilities to de...

  9. Dopamine Signaling in reward-related behaviors

    OpenAIRE

    Baik, Ja-Hyun

    2013-01-01

    Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specifi...

  10. Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

    Science.gov (United States)

    Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

    2017-10-01

    Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

  11. Dopamine and extinction: a convergence of theory with fear and reward circuitry.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2014-02-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Dopamine-dependent neurodegeneration in Drosophila models of familial and sporadic Parkinson's disease.

    Science.gov (United States)

    Bayersdorfer, Florian; Voigt, Aaron; Schneuwly, Stephan; Botella, José A

    2010-10-01

    Parkinson's disease has been found to be caused by both, genetic and environmental factors. Despite the diversity of causes involved, a convergent pathogenic mechanism might underlie the special vulnerability of dopaminergic neurons in different forms of Parkinsonism. In recent years, a number of reports have proposed dopamine as a common player responsible in the loss of dopaminergic neurons independent of its etiology. Using RNAi lines we were able to generate flies with drastically reduced dopamine levels in the dopaminergic neurons. Combining these flies with a chemically induced Parkinson model (rotenone) and a familial form of Parkinson (mutant alpha-synuclein) we were able to show a strong reduction of neurotoxicity and a protection of the dopaminergic neurons when cellular dopamine levels were reduced. These results show that dopamine homeostasis plays a central role for the susceptibility of dopaminergic neurons to environmental and genetic factors in in vivo models of Parkinson disease. (c) 2010 Elsevier Inc. All rights reserved.

  13. Assessing the vulnerability of public-supply wells to contamination--Glacial aquifer system in Woodbury, Connecticut

    Science.gov (United States)

    Jagucki, Martha L.; Brown, Craig J.; Starn, J. Jeffrey; Eberts, Sandra M.

    2010-01-01

    This fact sheet highlights findings from the vulnerability study of a public-supply well in Woodbury, Connecticut. The well typically produces water at the rate of 72 gallons per minute from the glacial aquifer system in the Pomperaug River Basin. Water samples were collected at the public-supply well and at monitoring wells installed in or near the simulated zone of contribution to the supply well. Samples of untreated water from the public-supply wellhead contained several types of undesirable constituents, including 11 volatile organic compounds (VOCs), nitrate, pesticides, uranium, and radon. Most of these constituents were detected at concentrations below drinking-water standards, where such standards exist. Only concentrations of the VOC trichlorethylene exceeded the Maximum Contaminant Level (MCL) of 5 micrograms per liter (ug/L) established by U.S. Environmental Protection Agency for drinking water. Radon concentrations exceeded a proposed-but not finalized-MCL of 300 picocuries per liter (pCi/L). Overall, the study findings point to four main factors that affect the movement and fate of contaminants and the vulnerability of the public-supply well in Woodbury: (1) groundwater age (how long ago water entered, or recharged, the aquifer); (2) the percentage of recharge received through urban areas; (3) the percentage of recharge received through dry wells and their proximity to the public-supply well; and (4) natural geochemical processes occurring within the aquifer system; that is, processes that affect the amounts and distribution of chemical substances in aquifer sediments and groundwater. A computer-model simulation of groundwater flow to the public-supply well was used to estimate the age of water particles entering the well along the length of the well screen. About 90 percent of the simulated flow to the well consists of water that entered the aquifer 9 or fewer years ago. Such young water is vulnerable to contaminants resulting from human activities

  14. Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

    OpenAIRE

    Gantz, Stephanie C.; Levitt, Erica S.; Llamosas Muñozguren, Nerea; Neve, Kim A.; Williams, John T.

    2015-01-01

    Imbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson's disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC) in dopamine neurons of the substantia nigr...

  15. Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

    Science.gov (United States)

    Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

    The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant No. 14-04-00173.

  16. Immunomodulatory Effects Mediated by Dopamine

    Science.gov (United States)

    Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

    2016-01-01

    Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

  17. Immunomodulatory Effects Mediated by Dopamine

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2016-01-01

    Full Text Available Dopamine (DA, a neurotransmitter in the central nervous system (CNS, has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R and D2-like receptors (D2R, D3R, and D4R. The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS, there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

  18. Safeguard Vulnerability Analysis Program (SVAP)

    International Nuclear Information System (INIS)

    Gilman, F.M.; Dittmore, M.H.; Orvis, W.J.; Wahler, P.S.

    1980-01-01

    This report gives an overview of the Safeguard Vulnerability Analysis Program (SVAP) developed at Lawrence Livermore National Laboratory. SVAP was designed as an automated method of analyzing the safeguard systems at nuclear facilities for vulnerabilities relating to the theft or diversion of nuclear materials. SVAP addresses one class of safeguard threat: theft or diversion of nuclear materials by nonviolent insiders, acting individually or in collusion. SVAP is a user-oriented tool which uses an interactive input medium for preprocessing the large amounts of safeguards data. Its output includes concise summary data as well as detailed vulnerability information

  19. Dopamine and glucose, obesity and Reward Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Kenneth eBlum

    2014-09-01

    Full Text Available Obesity and many well described eating disorders are accurately considered a global epidemic. The consequences of Reward Deficiency Syndrome, a genetic and epigenetic phenomena that involves the interactions of powerful neurotransmitters, are impairments of brain reward circuitry, hypodopaminergic function and abnormal craving behavior. Numerous sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Important facts which could translate to potential therapeutic targets espoused in this review include: 1 brain dopamine (DA production and use is stimulated by consumption of alcohol in large quantities or carbohydrates bingeing; 2 in the mesolimbic system the enkephalinergic neurons are in close proximity, to glucose receptors; 3 highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; 4 blood glucose and cerebrospinal fluid concentrations of homovanillic acid, the dopamine metabolite, are significantly correlated and 5 2-deoxyglucose the glucose analogue, in pharmacological doses associates with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and human fMRI support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and DA-modulated reward circuits are involved in pathologic eating behaviors. Treatment for addiction to glucose and drugs alike, based on a consensus of neuroscience research, should incorporate dopamine agonist therapy, in contrast to current theories and practices that use dopamine antagonists. Until now, powerful dopamine-D2 agonists have failed clinically, due to chronic down regulation of D2 receptors instead, consideration of novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of

  20. Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.

    Science.gov (United States)

    Farré, Daniel; Muñoz, Ana; Moreno, Estefanía; Reyes-Resina, Irene; Canet-Pons, Júlia; Dopeso-Reyes, Iria G; Rico, Alberto J; Lluís, Carme; Mallol, Josefa; Navarro, Gemma; Canela, Enric I; Cortés, Antonio; Labandeira-García, José L; Casadó, Vicent; Lanciego, José L; Franco, Rafael

    2015-12-01

    Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.

  1. The relationship between peak warming and cumulative CO2 emissions, and its use to quantify vulnerabilities in the carbon-climate-human system

    International Nuclear Information System (INIS)

    Raupach, Michael; Canadell, Josep G.; Ciais, Philippe; Friedlingstein, Pierre; Rayner, Peter J.; Trudinger, Catherine M.

    2011-01-01

    Interactions between the carbon cycle, climate and human societies are subject to several major vulnerabilities, broadly defined as factors contributing to the risk of harm from human-induced climate change. We assess five vulnerabilities: (1) effects of increasing CO 2 on the partition of anthropogenic carbon between atmospheric, land and ocean reservoirs; (2) effects of climate change (quantified by temperature) on CO 2 fluxes; (3) uncertainty in climate sensitivity; (4) non-CO 2 radiative forcing and (5) anthropogenic CO 2 emissions. Our analysis uses a physically based expression for Tp(Qp), the peak warming Tp associated with a cumulative anthropogenic CO 2 emission Qp to the time of peak warming. The approximations in this expression are evaluated using a non-linear box model of the carbon-climate system, forced with capped emissions trajectories described by an analytic form satisfying integral and smoothness constraints. The first four vulnerabilities appear as parameters that influence Tp(Qp), whereas the last appears through the independent variable. In terms of likely implications for Tp(Qp), the decreasing order of the first four vulnerabilities is: uncertainties in climate sensitivity, effects of non-CO 2 radiative forcing, effects of climate change on CO 2 fluxes and effects of increasing CO 2 on the partition of anthropogenic carbon. (authors)

  2. Applications of network analysis for adaptive management of artificial drainage systems in landscapes vulnerable to sea level rise

    Science.gov (United States)

    Poulter, Benjamin; Goodall, Jonathan L.; Halpin, Patrick N.

    2008-08-01

    SummaryThe vulnerability of coastal landscapes to sea level rise is compounded by the existence of extensive artificial drainage networks initially built to lower water tables for agriculture, forestry, and human settlements. These drainage networks are found in landscapes with little topographic relief where channel flow is characterized by bi-directional movement across multiple time-scales and related to precipitation, wind, and tidal patterns. The current configuration of many artificial drainage networks exacerbates impacts associated with sea level rise such as salt-intrusion and increased flooding. This suggests that in the short-term, drainage networks might be managed to mitigate sea level rise related impacts. The challenge, however, is that hydrologic processes in regions where channel flow direction is weakly related to slope and topography require extensive parameterization for numerical models which is limited where network size is on the order of a hundred or more kilometers in total length. Here we present an application of graph theoretic algorithms to efficiently investigate network properties relevant to the management of a large artificial drainage system in coastal North Carolina, USA. We created a digital network model representing the observation network topology and four types of drainage features (canal, collector and field ditches, and streams). We applied betweenness-centrality concepts (using Dijkstra's shortest path algorithm) to determine major hydrologic flowpaths based off of hydraulic resistance. Following this, we identified sub-networks that could be managed independently using a community structure and modularity approach. Lastly, a betweenness-centrality algorithm was applied to identify major shoreline entry points to the network that disproportionately control water movement in and out of the network. We demonstrate that graph theory can be applied to solving management and monitoring problems associated with sea level rise

  3. Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

    Directory of Open Access Journals (Sweden)

    Roger Cachope

    2012-07-01

    Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

  4. Ventral tegmental area dopamine revisited: effects of acute and repeated stress

    Science.gov (United States)

    Holly, Elizabeth N.; Miczek, Klaus A.

    2015-01-01

    Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression. PMID:26676983

  5. The Dopamine Receptor D4 Gene ("DRD4") Moderates Family Environmental Effects on ADHD

    Science.gov (United States)

    Martel, Michelle M.; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Waldman, Irwin; Nigg, Joel T.

    2011-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a prime candidate for exploration of gene-by-environment interaction (i.e., G x E), particularly in relation to dopamine system genes, due to strong evidence that dopamine systems are dysregulated in the disorder. Using a G x E design, we examined whether the "DRD4" promoter 120-bp tandem repeat…

  6. Neuropharmacology of novel dopamine modulators

    NARCIS (Netherlands)

    Beek, Erik Tomas te

    2014-01-01

    De neurotransmitter dopamine speelt een essentiële rol in diverse neurofysiologische functies en is betrokken bij de pathofysiologie van diverse neuropsychiatrische aandoeningen, waaronder de ziekte van Parkinson, schizofrenie, drugsverslaving en hyperprolactinemie. De huidige

  7. Dopamine signaling: target in glioblastoma

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk

    2014-01-01

    Roč. 5, č. 5 (2014), 1116-1117 ISSN 1949-2553 Institutional support: RVO:68378050 Keywords : Dopamine signaling * glioblastoma * MAPK Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.359, year: 2014

  8. Dopamine reward prediction error coding.

    Science.gov (United States)

    Schultz, Wolfram

    2016-03-01

    Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards-an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware.

  9. Assessing the Vulnerability of Public-Supply Wells to Contamination: Central Valley Aquifer System near Modesto, California

    Science.gov (United States)

    Jagucki, Martha L.; Jurgens, Bryant C.; Burow, Karen R.; Eberts, Sandra M.

    2009-01-01

    This fact sheet highlights findings from the vulnerability study of a public-supply well in Modesto, California. The well selected for study pumps on average about 1,600 gallons per minute from the Central Valley aquifer system during peak summer demand. Water samples were collected at the public-supply well and at monitoring wells installed in the Modesto vicinity. Samples from the public-supply wellhead contained the undesirable constituents uranium, nitrate, arsenic, volatile organic compounds (VOCs), and pesticides, although none were present at concentrations exceeding drinking-water standards. Of these contaminants, uranium and nitrate pose the most significant water-quality risk to the public-supply well because human activities have caused concentrations in groundwater to increase over time. Overall, study findings point to four primary factors that affect the movement and (or) fate of contaminants and the vulnerability of the public-supply well in Modesto: (1) groundwater age (how long ago water entered, or recharged, the aquifer); (2) irrigation and agricultural and municipal pumping that drives contaminants downward into the primary production zone of the aquifer; (3) short-circuiting of contaminated water down the public-supply well during the low-pumping season; and (4) natural geochemical conditions of the aquifer. A local-scale computer model of groundwater flow and transport to the public-supply well was constructed to simulate long-term nitrate and uranium concentrations reaching the well. With regard to nitrate, two conflicting processes influence concentrations in the area contributing recharge to the well: (1) Beneath land that is being farmed or has recently been farmed (within the last 10 to 20 years), downward-moving irrigation waters contain elevated nitrate concentrations; yet (2) the proportion of agricultural land has decreased and the proportion of urban land has increased since 1960. Urban land use is associated with low nitrate

  10. Vulnerability in farmer seed systems: Farmer practices for coping with seed insecurity for sorghum in Eastern Ethiopia

    NARCIS (Netherlands)

    McGuire, S.J.

    2007-01-01

    Many interventions try to address farmers¿ seed insecurity, though few assess the causes of farmers¿ vulnerability or understand their coping strategies. This paper analyzes farmers¿ practices for maintaining sorghum seed security in a specific season (1998¿99) in Ethiopia, which provides a richer

  11. A global drought monitoring system: insights of an approach integrating remote sensing data and vulnerability to food insecurity

    Science.gov (United States)

    Angeluccetti, Irene; Perez, Francesca; Cámaro, Walther; Demarchi, Alessandro

    2015-04-01

    Early Warning Systems (EWS) for drought are currently underdeveloped compared to those related to other natural hazards. Both forecasting and monitoring of drought events are still posing challenges to the scientific community. In fact, the multifaceted nature of drought (i.e. hydrological, meteorological, and agricultural) is source of coexistence for different ways to measure this phenomenon and its effects. Similarly, drought impacts are various and complex thus difficult to be univocally measured. In the present study an approach for monitoring drought in near-real time and for estimating its impacts is presented. The EWS developed runs on a global extent and is mainly based on the early detection and monitoring of vegetation stress. On the one hand the monitoring of vegetation phenological parameters, whose extraction is based on the analysis of the MODIS-derived NDVI function, allows the fortnightly assessment of the vegetation productivity which could be expected at the end of the growing season. On the other hand, the Standardized Precipitation Index (SPI), calculated adapting TRMM-derived precipitation data in a selected distribution is used, before the growing season start, in order to early detect meteorological conditions which could give rise to vegetation stress events. During the growing season the SPI is used as check information for vegetation conditions. The relationships between rainfall and vegetation dynamics have been statistically analyzed considering different types of vegetation, in order to identify the most suitable rainfall cumulating interval to be used for the proposed monitoring procedures in different areas. A simplified vulnerability model, coupled with the above-mentioned hazard data, returns food security conditions, i.e. the estimated impacts over an investigated area. The model includes a set of agricultural indicators that accounts for the diversity of cultivated crops, the percentage of irrigated area and the suitability of

  12. Dopamine, behavioral economics, and effort

    Directory of Open Access Journals (Sweden)

    John D Salamone

    2009-09-01

    Full Text Available Abstract. There are numerous problems with the hypothesis that brain dopamine (DA systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding to other concepts and lines of inquiry. The present review is focused upon the involvement of nucleus accumbens DA in behavioral activation and effort-related processes. Viewed from the framework of behavioral economics, the effects of accumbens DA depletions and antagonism on food-reinforced behavior are highly dependent upon the work requirements of the instrumental task, and DA depleted rats are more sensitive to increases in response costs (i.e., ratio requirements. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related choice behavior. Rats with accumbens DA depletions or antagonism reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead these rats select a less-effortful type of food-seeking behavior. Nucleus accumbens DA and adenosine interact in the regulation of effort-related functions, and other brain structures (anterior cingulate cortex, amygdala, ventral pallidum also are involved. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue or anergia in depression and other neurological disorders.

  13. [Effect of Corydalis Rhizoma and L-tetrahydropalmatine on dopamine system of hippocampus and striatum in morphine-induced conditioned place preference rats].

    Science.gov (United States)

    Yu, Shou-Yang; Bai, Wei-Feng; Tu, Ping; Qiu, Cheng-Kai; Yang, Pei-Run; Luo, Su-Yuan

    2016-10-01

    To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹). Models of CPP were validated in those psychological dependence rats after 48 h training. The dopamine contents were detected as soon as the materials of hippocampus and striatum are harvested from rats of NS control group and model group. The DAT and D2R levels are measured by Western blot. The high, medium and low dose group of Corydalis Rhizoma are given Corydalis Rhizoma 2, 1, 0.5 g•kg⁻¹ water extraction liquid respectively (which contains L-THP were 0.274, 0.137 and 0.137 mg respectively), and the high, medium and low dose group of L-THP were given L-THP 3.76, 1.88, 0.94 mg•kg⁻¹ lavage treatment respectively, NS treatment group were lavaged normal saline for 6 days and they were killed after test of CPP, again tested DA levels and expression of DAT and D2R similar to the front of materials. The reduction effects of CPP were observed in the groups of both Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) subjected to medicine for 6 days (Peffect of L-THP. The similar effects were observed on the neurotransmitter dopamine, DAT and D2R in learning and memory-related brain areas, hippocampus and striatum of the morphine- dependent rats. Copyright© by the Chinese Pharmaceutical Association.

  14. Commercial Air Carrier Vulnerabilities to Information Operations

    National Research Council Canada - National Science Library

    Shelburn, Bryan H

    2002-01-01

    .... The increasing dependence of government and industry on information technology has created critical vulnerabilities that can be exploited by degrading or destroying the use of information systems...

  15. Dopamine and extinction: A convergence of theory with fear and reward circuitry

    Science.gov (United States)

    Abraham, Antony D.; Neve, Kim A.; Lattal, K. Matthew

    2014-01-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine’s function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. PMID:24269353

  16. A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

    Science.gov (United States)

    Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

    Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

  17. Addiction: beyond dopamine reward circuitry.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Fowler, Joanna S; Tomasi, Dardo; Telang, Frank

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  18. Imaging dopamine transmission in schizophrenia

    International Nuclear Information System (INIS)

    Laruelle, M.

    1998-01-01

    Over the last ten years, several positron emission tomography (PET) and single photon computerized tomography (SPECT) studies of the dopamine (DA) system in patients with schizophrenia were performed to test the hypothesis that DA hyperactivity is associated with this illness. In this paper are reviewed the results of fifteen brain imaging studies comparing indices of DA function in drug naive or drug free patients with schizophrenia and healthy controls: thirteen studies included measurements of Da D 2 receptor density, two studies compared amphetamine-induced DA release, and two studies measured DOPA decarboxylase activity, an enzyme involved in DA synthesis. It was conducted a meta-analysis of the studies measuring D 2 receptor density parameters, under the assumption that all tracers labeled the same population of D 2 receptors. This analysis revealed that, compared to healthy controls, patients with schizophrenia present a significant but mild elevation of D 2 receptor density parameters and a significant larger variability of these indices. It was found no statistical evidence that studies performed with radiolabeled butyrophenones detected a larger increase in D 2 receptor density parameters than studies performed with other radioligands, such as benzamides. Studies of presynaptic activity revealed an increase in DA transmission response to amphetamine challenge, and an increase in DOPA decarboxylase activity. Together, these data are compatible with both pre- and post-synaptic alterations of DA transmission in schizophrenia. Future studies should aim at a better characterization of these alterations, and at defining their role in the pathophysiology of the illness

  19. Addiction: Beyond dopamine reward circuitry

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.

    2011-01-01

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  20. Addiction: Beyond dopamine reward circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  1. Region-specific vulnerability to lipid peroxidation and evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the healthy adult human central nervous system.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Dominguez-Gonzalez, Mayelin; Ayala, Victoria; Jové, Mariona; Mota-Martorell, Natalia; Piñol-Ripoll, Gerard; Gil-Villar, Maria Pilar; Rué, Montserrat; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2017-05-01

    Lipids played a determinant role in the evolution of the brain. It is postulated that the morphological and functional diversity among neural cells of the human central nervous system (CNS) is projected and achieved through the expression of particular lipid profiles. The present study was designed to evaluate the differential vulnerability to oxidative stress mediated by lipids through a cross-regional comparative approach. To this end, we compared 12 different regions of CNS of healthy adult subjects, and the fatty acid profile and vulnerability to lipid peroxidation, were determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), respectively. In addition, different components involved in PUFA biosynthesis, as well as adaptive defense mechanisms against lipid peroxidation, were also measured by western blot and immunohistochemistry, respectively. We found that: i) four fatty acids (18.1n-9, 22:6n-3, 20:1n-9, and 18:0) are significant discriminators among CNS regions; ii) these differential fatty acid profiles generate a differential selective neural vulnerability (expressed by the peroxidizability index); iii) the cross-regional differences for the fatty acid profiles follow a caudal-cranial gradient which is directly related to changes in the biosynthesis pathways which can be ascribed to neuronal cells; and iv) the higher the peroxidizability index for a given human brain region, the lower concentration of the protein damage markers, likely supported by the presence of adaptive antioxidant mechanisms. In conclusion, our results suggest that there is a region-specific vulnerability to lipid peroxidation and offer evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the human central nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease.

    Science.gov (United States)

    Pissadaki, Eleftheria K; Bolam, J Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD.

  3. Blockade of Dopamine Activity in the Nucleus Accumbens Impairs Learning Extinction of Conditioned Fear

    Science.gov (United States)

    Holtzman-Assif, Orit; Laurent, Vincent; Westbrook, R. Frederick

    2010-01-01

    Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In…

  4. Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice

    DEFF Research Database (Denmark)

    Thomsen, Annika Højrup Runegaard; Jensen, Kathrine L; Fitzpatrick, Ciarán M

    2017-01-01

    assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice...

  5. A role for accumbal glycine receptors in modulation of dopamine release by the glycine transporter-1 inhibitor Org25935

    Directory of Open Access Journals (Sweden)

    Helga eHöifödt Lidö

    2011-03-01

    Full Text Available AbstractAccumbal glycine modulates basal and ethanol-induced dopamine levels in the nucleus accumbens (nAc as well as voluntary ethanol consumption. Also, systemic administration of the glycine transporter-1 inhibitor Org25935 elevates dopamine levels in nAc, prevents a further ethanol-induced dopamine elevation and robustly and dose-dependently decreases ethanol consumption in rats. Here we investigated whether Org25935 applied locally in nAc modulates dopamine release, and whether accumbal glycine receptors or NMDA receptors are involved in this tentative effect. We also addressed whether Org25935 and ethanol applied locally in nAc interact with dopamine levels, as seen after systemic administration. We used in vivo microdialysis coupled to HPLC-ED in freely moving male Wistar rats to monitor dopamine output in nAc after local perfusion of Org25935 alone, with ethanol, or Org25935-perfusion after pre-treatment with the glycine receptor antagonist strychnine or the NMDA receptor glycine site antagonist L-701.324. Local Org25935 increased extracellular dopamine levels in a subpopulation of rats. Local strychnine, but not systemic L-701.324, antagonized the dopamine-activating effect of Org25935. Ethanol failed to induce a dopamine overflow in the subpopulation responding to Org25935 with a dopamine elevation. The study supports a role for accumbal glycine receptors rather than NMDA receptor signaling in the dopamine-activating effect of Org25935. The results further indicate that the previously reported systemic Org25935-ethanol interaction with regard to accumbal dopamine is localized to the nAc. This adds to the growing evidence for the glycine receptor as an important player in the dopamine reward circuitry and in ethanol’s effects within this system.

  6. Dopamine alleviates nutrient deficiency-induced stress in Malus hupehensis.

    Science.gov (United States)

    Liang, Bowen; Li, Cuiying; Ma, Changqing; Wei, Zhiwei; Wang, Qian; Huang, Dong; Chen, Qi; Li, Chao; Ma, Fengwang

    2017-10-01

    Dopamine mediates many physiological processes in plants. We investigated its role in regulating growth, root system architecture, nutrient uptake, and responses to nutrient deficiencies in Malus hupehensis Rehd. Under a nutrient deficiency, plants showed significant reductions in growth, chlorophyll concentrations, and net photosynthesis, along with disruptions in nutrient uptake, transport, and distribution. However, pretreatment with 100 μM dopamine markedly alleviated such inhibitions. Supplementation with that compound enabled plants to maintain their photosynthetic capacity and development of the root system while promoting the uptake of N, P, K, Ca, Mg, Fe, Mn, Cu, Zn, and B, altering the way in which those nutrients were partitioned throughout the plant. The addition of dopamine up-regulated genes for antioxidant enzymes involved in the ascorbate-glutathione cycle (MdcAPX, MdcGR, MdMDHAR, MdDHAR-1, and MdDHAR-2) but down-regulated genes for senescence (SAG12, PAO, and MdHXK). These results indicate that exogenous dopamine has an important antioxidant and anti-senescence effect that might be helpful for improving nutrient uptake. Our findings demonstrate that dopamine offers new opportunities for its use in agriculture, especially when addressing the problem of nutrient deficiencies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Dopamine, reward learning, and active inference

    Directory of Open Access Journals (Sweden)

    Thomas eFitzgerald

    2015-11-01

    Full Text Available Temporal difference learning models propose phasic dopamine signalling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behaviour. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

  8. Dopamine, reward learning, and active inference.

    Science.gov (United States)

    FitzGerald, Thomas H B; Dolan, Raymond J; Friston, Karl

    2015-01-01

    Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

  9. Behavioural effects of chemogenetic dopamine neuron activation

    NARCIS (Netherlands)

    Boekhoudt, L

    2016-01-01

    Various psychiatric disorders, including schizophrenia, attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder, have been associated with altered dopamine signalling in the brain. However, it remains unclear which specific changes in dopamine activity are related to specific

  10. Molecular Mechanisms of Dopamine Receptor Mediated Neuroprotection

    National Research Council Canada - National Science Library

    Sealfon, Stuart

    2000-01-01

    ... of the cellular changes characteristic of this process. Evidence from our laboratory and others suggest that activation of dopamine receptors can oppose the induction of apoptosis in dopamine neurons...

  11. Conceptual and experimental approach to the vulnerability of human resources in the evolving structure of the national power system to 2030 period

    Energy Technology Data Exchange (ETDEWEB)

    Dan Gheorghiu, Ioan; Visa, Ion; Carabulea, Anatol; Morar, Adrian; Popper, Laurentiu; Popper, Gabriel; Bucur, Camelia

    2010-09-15

    We present the causes generating vulnerabilities and propose the models for diminishing the risks and catastrophes based on the education of the human resources incorporated in the evolution of the local power system and not only. We specify the fuzzy structure of the model for increasing the quality of the human factor and of the models for rating the human resources in power plants and the networks of the power systems exemplified on the evolving structure of the Romanian installations subject to dynamic reconfiguring over the forecast interval (2020 - 2035).

  12. spatially identifying vulnerable areas

    African Journals Online (AJOL)

    The model structure is aimed at understanding the critical vulnerable factors that ... This paper incorporates multiple criteria and rank risk factors. ..... In terms of quantifying vulnerable areas within the country, the analysis is done based on 9 ...

  13. Fuzzing and Vulnerabilities Search

    OpenAIRE

    Stanislav Evgenyevich Kirillov; Nikolai Petrovich Lavrentiev

    2013-01-01

    Fuzzing for vulnerabilities can be very effective if we know the input data format. This work contains description of network message format recovery algorithm and the usage of restored data model in fuzzing and vulnerabilities search.

  14. Fuzzing and Vulnerabilities Search

    Directory of Open Access Journals (Sweden)

    Stanislav Evgenyevich Kirillov

    2013-02-01

    Full Text Available Fuzzing for vulnerabilities can be very effective if we know the input data format. This work contains description of network message format recovery algorithm and the usage of restored data model in fuzzing and vulnerabilities search.

  15. Assessing the vulnerability of public-supply wells to contamination: Rio Grande aquifer system in Albuquerque, New Mexico

    Science.gov (United States)

    Jagucki, Martha L.; Bexfield, Laura M.; Heywood, Charles E.; Eberts, Sandra M.

    2012-01-01

    This fact sheet highlights findings from the vulnerability study of a public-supply well in Albuquerque, New Mexico (hereafter referred to as “the study well”). The study well produces about 3,000 gallons of water per minute from the Rio Grande aquifer system. Water samples were collected at the study well, at two other nearby public-supply wells, and at monitoring wells installed in or near the simulated zone of contribution to the study well. Untreated water samples from the study well contained arsenic at concentrations exceeding the Maximum Contaminant Level (MCL) of 10 micrograms per liter (µg/L) established by the U.S. Environmental Protection Agency for drinking water. Volatile organic compounds (VOCs) and nitrate also were detected, although at concentrations at least an order of magnitude less than established drinking-water standards, where such standards exist. Overall, study findings point to four primary influences on the movement and (or) fate of contaminants and the vulnerability of the public-supply well in Albuquerque: (1) groundwater age (how long ago water entered, or recharged, the aquifer), (2) groundwater development (introduction of manmade recharge and discharge sources), (3) natural geochemical conditions of the aquifer, and (4) seasonal pumping stresses. Concentrations of the isotope carbon-14 indicate that groundwater from most sampled wells in the local study area is predominantly water that entered, or recharged, the aquifer more than 6,000 years ago. However, the additional presence of the age tracer tritium in several groundwater samples at concentrations above 0.3 tritium units indicates that young (post-1950) recharge is reaching the aquifer across broad areas beneath Albuquerque. This young recharge is mixing with the thousands-of-years-old water, is migrating to depths as great as 245 feet below the water table, and is traveling to some (but not all) of the public-supply wells sampled. Most groundwater samples containing a

  16. Environmental smoking and smoking onset in adolescence: the role of dopamine-related genes. Findings from two longitudinal studies.

    Directory of Open Access Journals (Sweden)

    Marieke Hiemstra

    Full Text Available Although environmental smoking (i.e., paternal and maternal smoking, sibling smoking, and peer smoking is one of the most important factors for explaining adolescent smoking behavior, not all adolescents are similarly affected. The extent to which individuals are vulnerable to smoking in their environment might depend on genetic factors. The aim of this study was to examine the interplay between environmental smoking and genes encoding components of the dopaminergic system (i.e., dopamine receptor D2, D4, and dopamine transporter DAT1 in adolescent smoking onset. Data from two longitudinal studies were used. Study 1 consisted of 991 non-smoking early adolescents (mean age = 12.52, SD = .57 whereas study 2 consisted of 365 non-smoking middle to late adolescents (mean age = 14.16, SD = 1.07 who were followed for 16 and 48 months, respectively. Logistic regression analyses were conducted using Mplus. In study 1, we found positive associations between parents' and friends' smoking at the first measurement and smoking status 16 months later. In study 2 we found a positive association between friends' smoking and smoking onset 48 months later. Neither study demonstrated any interaction effects of the DRD2, DRD4, or DAT1 genotypes. In conclusion, the effects of environmental smoking on smoking onset are similar for adolescent carriers and non-carriers of these specific genes related to the dopaminergic system.

  17. What Does Vulnerability Mean?

    Science.gov (United States)

    Parley, Fiona F

    2011-01-01

    Protection of those deemed vulnerable has received increasing attention since 2000. This article reports on care staff views of vulnerability using original data from a research study (Parley. "Vulnerability and abuse: an exploration of views of care staff working with people who have learning disabilities," PhD Thesis, 2007) in which care staff…

  18. HEPA Filter Vulnerability Assessment

    International Nuclear Information System (INIS)

    GUSTAVSON, R.D.

    2000-01-01

    This assessment of High Efficiency Particulate Air (HEPA) filter vulnerability was requested by the USDOE Office of River Protection (ORP) to satisfy a DOE-HQ directive to evaluate the effect of filter degradation on the facility authorization basis assumptions. Within the scope of this assessment are ventilation system HEPA filters that are classified as Safety-Class (SC) or Safety-Significant (SS) components that perform an accident mitigation function. The objective of the assessment is to verify whether HEPA filters that perform a safety function during an accident are likely to perform as intended to limit release of hazardous or radioactive materials, considering factors that could degrade the filters. Filter degradation factors considered include aging, wetting of filters, exposure to high temperature, exposure to corrosive or reactive chemicals, and exposure to radiation. Screening and evaluation criteria were developed by a site-wide group of HVAC engineers and HEPA filter experts from published empirical data. For River Protection Project (RPP) filters, the only degradation factor that exceeded the screening threshold was for filter aging. Subsequent evaluation of the effect of filter aging on the filter strength was conducted, and the results were compared with required performance to meet the conditions assumed in the RPP Authorization Basis (AB). It was found that the reduction in filter strength due to aging does not affect the filter performance requirements as specified in the AB. A portion of the HEPA filter vulnerability assessment is being conducted by the ORP and is not part of the scope of this study. The ORP is conducting an assessment of the existing policies and programs relating to maintenance, testing, and change-out of HEPA filters used for SC/SS service. This document presents the results of a HEPA filter vulnerability assessment conducted for the River protection project as requested by the DOE Office of River Protection

  19. ICMPv6 RA Flooding Vulnerability Research

    Directory of Open Access Journals (Sweden)

    Linas Jočys

    2016-06-01

    Full Text Available ICMPv6 is the newest version of internet control message protocol, whose main purpose is to send error message indicating packet processing failure. It is know that ICMPv6 is technologically vulnerable. One of those vulnerabilities is the ICMPv6 RA flooding vulnerability, which can lead to systems in Local Area Network slow down or full stop. This paper will discuss Windows (XP, 7, 8.1 and Linux Ubuntu 14 operating systems resistance to RA flooding attack research and countermeasures to minimize this vulnerability.

  20. Vulnerability maps for Druzba crude oil pipeline

    International Nuclear Information System (INIS)

    Hladik, P.; Hosnedl, P.; Buresova, H.; Corbet, J.

    2012-01-01

    Maps of risk for individual environmental aspects within the protection zone of the Czech part of the Druzba crude oil pipeline (505.7 km) were developed based on a modified 'H and V index' method. Risk data were added into a GIS of the Druzba pipeline so that the system could be used as conceptual material in the field of environmental protection (a base for the new SCADA system). Considered environmental aspects were assessed in terms of their vulnerability. The criteria were defined as the vulnerability of the aquatic environment (surface waters and ground waters), the vulnerability of soil environment and the vulnerability of biotic components of the environment. (authors)

  1. Reward-based hypertension control by a synthetic brain-dopamine interface.

    Science.gov (United States)

    Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

    2013-11-05

    Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

  2. Graphene Oxide Modified Electrodes for Dopamine Sensing

    Directory of Open Access Journals (Sweden)

    M. Z. H. Khan

    2017-01-01

    Full Text Available Dopamine (DA is one of the most important catecholamine neurotransmitters that plays an important role in the central nervous, renal, hormonal, and cardiovascular systems. Since its discovery, tremendous effort has been made and various techniques have been developed for the DA detection. Recently, graphene-based materials have attracted a tremendous amount of attention due to their high sensitivity and rapid response towards effective detection of DA. This review focuses on current advances of graphene-based materials for DA detection based on recent articles published in the last five years.

  3. Method of Pentest Synthesis and Vulnerability Detection

    OpenAIRE

    Hahanova Irina Vitalyevna

    2012-01-01

    The structural method for penetration test generation and vulnerability simulation for infrastructure of telecommunication hardwaresoftware information cybernetic systems (CS), focused to protect against unauthorized access the services defined in the system specification by means of penetrating through legal interfaces of component interaction, which have vulnerabilities, is proposed. A protection service infrastructure is created with cybersystem and maintains it during the life cycle, serv...

  4. The SAVI vulnerability assessment model

    International Nuclear Information System (INIS)

    Winblad, A.E.

    1987-01-01

    The assessment model ''Systematic Analysis of Vulnerability to Intrusion'' (SAVI) presented in this report is a PC-based path analysis model. It can provide estimates of protection system effectiveness (or vulnerability) against a spectrum of outsider threats including collusion with an insider adversary. It calculates one measure of system effectiveness, the probability of interruption P(I), for all potential adversary paths. SAVI can perform both theft and sabotage vulnerability analyses. For theft, the analysis is based on the assumption that adversaries should be interrupted either before they can accomplish removal of the target material from its normal location or removal from the site boundary. For sabotage, the analysis is based on the assumption that adversaries should be interrupted before completion of their sabotage task

  5. Red Team Operations to Assess Information Technology Vulnerabilities

    NARCIS (Netherlands)

    Veltman, M.; Parker, R.L.

    1999-01-01

    All Information and Communication Technology (ICT) systems have vulnerabilities. Weaknesses in these systems are introduced either during the specification, implementation or operational phase. Leaving aside these introduced vulnerabilities are intentional or unintentional, the fact remains that

  6. Prediction of Unmet Primary Care Needs for the Medically Vulnerable Post-Disaster: An Interrupted Time-Series Analysis of Health System Responses

    Directory of Open Access Journals (Sweden)

    Amy B. Martin

    2012-09-01

    Full Text Available Disasters serve as shocks and precipitate unanticipated disturbances to the health care system. Public health surveillance is generally focused on monitoring latent health and environmental exposure effects, rather than health system performance in response to these local shocks. The following intervention study sought to determine the long-term effects of the 2005 chlorine spill in Graniteville, South Carolina on primary care access for vulnerable populations. We used an interrupted time-series approach to model monthly visits for Ambulatory Care Sensitive Conditions, an indicator of unmet primary care need, to quantify the impact of the disaster on unmet primary care need in Medicaid beneficiaries. The results showed Medicaid beneficiaries in the directly impacted service area experienced improved access to primary care in the 24 months post-disaster. We provide evidence that a health system serving the medically underserved can prove resilient and display improved adaptive capacity under adverse circumstances (i.e., technological disasters to ensure access to primary care for vulnerable sub-groups. The results suggests a new application for ambulatory care sensitive conditions as a population-based metric to advance anecdotal evidence of secondary surge and evaluate pre- and post-health system surge capacity following a disaster.

  7. Methods to Secure Databases Against Vulnerabilities

    Science.gov (United States)

    2015-12-01

    for several languages such as C, C++, PHP, Java and Python [16]. MySQL will work well with very large databases. The documentation references...using Eclipse and connected to each database management system using Python and Java drivers provided by MySQL , MongoDB, and Datastax (for Cassandra...tiers in Python and Java . Problem MySQL MongoDB Cassandra 1. Injection a. Tautologies Vulnerable Vulnerable Not Vulnerable b. Illegal query

  8. Preparation of (7,8-3H) dopamine

    International Nuclear Information System (INIS)

    Shen Qiyuan; Tang Guozhong; Guo Zili

    1986-01-01

    Dopamine is a neurotransmitter in the central nervous system. (7,8- 3 H) dopamine is an important tracer for the study of physiological functions and metabolic processes. It was prepared by catalytic reduction of 3-hydroxy-4-methoxy-8-nitro-styrene with tritium gas. At the end of reaction, hydrobromic acid was added and heated to remove the methoxyl group. The crude product was purified by paper chromatography. The purity of (7,8- 3 H) dopamine was identified by IR, UV, PC and 3 H-NMR spectra. The radiochemical purity was over 95% and the specific activity was 1.26 x 10 12 Bq/mmol (34 Ci/mmol). The distribution of labelled tritium in molecule was shown as follows: 55.4% at position 7 and 44.6% at position 8

  9. The involvement of dopaminergic system on LH secretion Nelore heifers Sistema dopaminérgico na secreção de LH de novilhas Nelore

    Directory of Open Access Journals (Sweden)

    Silvia Helena Venturoli Perri

    2009-12-01

    Full Text Available The aim of this study was to evaluate the response of sulpiride administration (dopamine D2 antagonist, 0.59 m/kg body weight, s.c. and blood collected every 15 min for 10 h thereafter on Luteinizing Hormone (LH secretion in B. indicus pre-pubertal heifers at 8, 12 and 16 month of age. LH was quantified by RIA, sensitivity (0.039 ng/ml and CV (15.51%. In heifers given sulpiride treatment didn’t differ (P≥0.05 in LH concentration, total secretion area, peak total area, number of peaks, area of highest secretion peak and time to highest peak occurrence and maximum LH secretion, from control group. The results suggest absence of dopamine D2 antagonist effect on LH secretion in pre-pubertal Nellore heifers, didn’t neurotransmitter participating on sexual maturation.O presente trabalho foi realizado com o objetivo de investigar a variação na secreção do Hormônio Luteinizante (LH em resposta ao tratamento com sulpiride, antagonista de receptor (D2 dopaminérgico, com administração de 0,59mg/kg, s.c. e colheita de amostras de sangue a cada 15min, por 10h. Foram utilizadas 10 novilhas da raça Nelore pré-púberes, aos 8, 12 e 16 meses de idade. A concentração de LH foi quantificada por radioimunoensaio, e o coeficiente de variação intra, o interensaio e a sensibilidade dos ensaios de LH foram respectivamente de: 11,86%; 15,51%; 0,039ng/mL. O tratamento com sulpiride não diferiu na concentração média de LH, área total de secreção de LH e picos, número de picos, área do maior pico, tempo necessário ao aparecimento do maior pico de secreção de LH e amplitude máxima de LH, em comparação ao grupo controle. Os resultados indicam ausência de efeito da dopamina, através de receptores D2, durante a fase pré-púbere, em novilhas da raça Nelore, o que sinaliza a não participação como neurotransmissora na secreção de LH durante o processo de maturação sexual.

  10. Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data

    Science.gov (United States)

    2016-01-01

    The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS. PMID:27548680

  11. Study of the dopamine effect into cell solutions by impedance analysis

    Science.gov (United States)

    Paivana, G.; Apostolou, T.; Kaltsas, G.; Kintzios, S.

    2017-11-01

    Electrochemical Impedance Spectroscopy (EIS) has become a technique that is frequently used for biological assays. Impedance is defined as a complex - valued generalization of resistance and varies depending on its use per application field. In health sciences, bioimpedance is widely used as non-invasive and low cost alternative in many medical areas that provides valuable information about health status. This work focuses on assessing the effects of a bioactive substance applied to immobilized cells. Dopamine was used as a stimulant in order to implement impedance analysis with a specific type of cells. Dopamine constitutes one of the most important catecholamine neurotransmitters in both the mammalian central and peripheral nervous systems. The main purpose is to extract calibration curves at different frequencies with known dopamine concentrations in order to describe the behavior of cells applied to dopamine using an impedance measurement device. For comparison purposes, non-immobilized cells were tested for the same dopamine concentrations.

  12. Crosstalk between insulin and dopamine signaling: A basis for the metabolic effects of antipsychotic drugs.

    Science.gov (United States)

    Nash, Abigail I

    2017-10-01

    In the setting of rising rates of obesity and metabolic syndrome, characterized in part by hyperinsulinemia, it is increasingly important to understand the mechanisms that contribute to insulin dysregulation. The higher risk for metabolic syndrome imparted by antipsychotic medication use highlights one such mechanism. Though there is great variation in the number and types of signaling pathways targeted by these medications, the one common mechanism of action is through dopamine. Dopamine's effects on insulin signaling begin at the level of insulin secretion from the pancreas and continue through the central nervous system. In a reciprocal fashion, insulin also affects dopamine signaling, with specific effects on dopamine reuptake from the synapse. This review probes the dopamine-insulin connection to provide a comprehensive examination of how antipsychotics may contribute towards insulin resistance. Published by Elsevier B.V.

  13. Ih current is necessary to maintain normal dopamine fluctuations and sleep consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Alicia Gonzalo-Gomez

    Full Text Available HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep:activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest:activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels.

  14. Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms

    Science.gov (United States)

    dela Peña, Ike; Gevorkiana, Ruzanna; Shi, Wei-Xing

    2015-01-01

    The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs. PMID:26209364

  15. Climate change in Germany. Vulnerability and adaption of climate sensitive sectors; Klimawandel in Deutschland. Vulnerabilitaet und Anpassungsstrategien klimasensitiver Systeme

    Energy Technology Data Exchange (ETDEWEB)

    Zebisch, Marc; Grothmann, Torsten; Schroeter, Dagmar; Hasse, Clemens; Fritsch, Uta; Cramer, Wolfgang [Potsdam Institut fuer Klimaforschung, Potsdam (Germany)

    2005-08-15

    The objectives of this study were the following: documentation of existing knowledge on global change (and particularly climate change) in Germany and to analysis of its current and potential future impacts on seven climate-sensitive sectors (water management, agriculture, forestry, biodiversity/nature conservation, health, tourism and transport).; the evaluation of the present degree of adaptation and the adaptive capacity of these climate-sensitive sectors to global change; conclusions on the vulnerability to global change of sectors and regions in Germany by considering potential global change impacts, degrees of adaptation and adaptive capacity; and the discussion of the results of the study with decision-makers from government, administration, economy and society, in order to develop a basis for the development of strategies of adaptation to global change in Germany.

  16. A modeling ontology for integrating vulnerabilities into security requirements conceptual foundations

    NARCIS (Netherlands)

    Elahi, G.; Yu, E.; Zannone, N.; Laender, A.H.F.; Castano, S.; Dayal, U.; Casati, F.; Palazzo Moreira de Oliveira, J.

    2009-01-01

    Vulnerabilities are weaknesses in the requirements, design, and implementation, which attackers exploit to compromise the system. This paper proposes a vulnerability-centric modeling ontology, which aims to integrate empirical knowledge of vulnerabilities into the system development process. In

  17. New approach to analyzing vulnerability

    International Nuclear Information System (INIS)

    O'Callaghan, P.B.; Carlson, R.L.; Riedeman, G.W.

    1986-01-01

    The Westinghouse Hanford Company (WHC) has recently completed construction of the Fuel Cycle Plant (FCP) at Richland, Washington. At start-up the facility will fabricate driver fuel for the Fast Flux Test Facility in the Secure Automated Fabrication line. After construction completion, but before facility certification, the Department of Energy (DOE) Richland Operation Office requested that a vulnerability analysis be performed which assumed multiple insiders as a threat to the security system. A unique method of analyzing facility vulnerabilities was developed at the Security Applications Center (SAC), which is managed by WHC for DOE. The method that was developed verifies a previous vulnerability assessment, as well as introducing a modeling technique which analyzes security alarms in relation to delaying factors and possible insider activities. With this information it is possible to assess the relative strength or weakness of various possible routes to and from a target within a facility

  18. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

    Science.gov (United States)

    Baskerville, Tracey A; Douglas, Alison J

    2010-06-01

    Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

  19. Imaging of dopamine release induced by pharmacologic and nonpharmacologic stimulations

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Technological advances in molecular imaging made it possible to image synaptic neurotransmitter concentration in living human brain. The dopaminergic system has been most intensively studied because of its importance in neurological as well as psychiatric disorders. This paper provides a brief overview of recent progress in imaging studies of dopamine release induced by pharmacologic and nonpharmacologic stimulations.

  20. Dopamine natriuresis in salt-repleted, water-loaded humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Olsen, M H; Bonde, J

    1997-01-01

    The purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 microg kg(-1) min(-1) in normal volunteers....

  1. Does activation of midbrain dopamine neurons promote or reduce feeding?

    NARCIS (Netherlands)

    Boekhoudt, L.; Roelofs, T. J.M.; de Jong, J. W.; de Leeuw, A. E.; Luijendijk, M. C.M.; Wolterink-Donselaar, I. G.; van der Plasse, G.; Adan, R. A.H.

    Background:Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced

  2. Does activation of midbrain dopamine neurons promote or reduce feeding?

    NARCIS (Netherlands)

    Boekhoudt, L.; Roelofs, T. J. M.; de Jong, J. W.; de Leeuw, A. E.; Luijendijk, M. C. M.; Wolterink-Donselaar, I. G.; van der Plasse, G.; Adan, R. A. H.

    2017-01-01

    BACKGROUND: Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced

  3. Mining Bug Databases for Unidentified Software Vulnerabilities

    Energy Technology Data Exchange (ETDEWEB)

    Dumidu Wijayasekara; Milos Manic; Jason Wright; Miles McQueen

    2012-06-01

    Identifying software vulnerabilities is becoming more important as critical and sensitive systems increasingly rely on complex software systems. It has been suggested in previous work that some bugs are only identified as vulnerabilities long after the bug has been made public. These vulnerabilities are known as hidden impact vulnerabilities. This paper discusses the feasibility and necessity to mine common publicly available bug databases for vulnerabilities that are yet to be identified. We present bug database analysis of two well known and frequently used software packages, namely Linux kernel and MySQL. It is shown that for both Linux and MySQL, a significant portion of vulnerabilities that were discovered for the time period from January 2006 to April 2011 were hidden impact vulnerabilities. It is also shown that the percentage of hidden impact vulnerabilities has increased in the last two years, for both software packages. We then propose an improved hidden impact vulnerability identification methodology based on text mining bug databases, and conclude by discussing a few potential problems faced by such a classifier.

  4. VULNERABILITY OF COMPANIES

    Directory of Open Access Journals (Sweden)

    ARMEAN ANDREEA

    2013-06-01

    Full Text Available In present, the study of vulnerability of companies is increasing in every field due to the unstable economic environment influences. The object of this research is to define and identify vulnerabilities of companies and the establishment of evaluation methods at their level. This article emphasizes the importance and usefulness of one of the best known model in this way, from our point of view, namely Băileşteanu, Negrila Pattern. This pattern covers both external factors and internal ones, that increase vulnerabilities of companies, and fit the companies in which the state of vulnerability are (vitality, viability, vulnerability, high vulnerability, difficulty and high difficulty, with a matrix. The result of the research is that any company belonging to any field, can be analyzed using this model, and assigned to one of the conditions defined within.

  5. A Critical Analysis of Vulnerability Taxonomies

    National Research Council Canada - National Science Library

    Bishop, Matt; Bailey, David

    1996-01-01

    Computer vulnerabilities seem to be omnipresent. In every system fielded programming errors configuration errors and operation errors have allowed unauthorized users to enter systems or authorized users to take unauthorized actions...

  6. Analysis of Zero-Day Vulnerabilities in Java

    OpenAIRE

    Marius Popa

    2013-01-01

    The zero-day vulnerability is a security lack of the computer system that is unknown to software vendor. This kind of vulnerability permits building attack strategies for gaining the access to the resources and data of a computer system. The main issue of the topic is how a computer system can be protected by zero-day vulnerabilities using the actual security procedures and tools for identifying the potential attacks that exploit the vulnerabilities unknown to computer users and software prov...

  7. Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

    Directory of Open Access Journals (Sweden)

    Pierre eTrifilieff

    2013-06-01

    Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

  8. A fluorescent sensor based on thioglycolic acid capped cadmium sulfide quantum dots for the determination of dopamine

    Science.gov (United States)

    Kulchat, Sirinan; Boonta, Wissuta; Todee, Apinya; Sianglam, Pradthana; Ngeontae, Wittaya

    2018-05-01

    A fluorescent sensor based on thioglycolic acid-capped cadmium sulfide quantum dots (TGA-CdS QDs) has been designed for the sensitive and selective detection of dopamine (DA). In the presence of dopamine (DA), the addition of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) activates the reaction between the carboxylic group of the TGA and the amino group of dopamine to form an amide bond, quenching the fluorescence of the QDs. The fluorescence intensity of TGA-CdS QDs can be used to sense the presence of dopamine with a limit of detection of 0.68 μM and a working linear range of 1.0-17.5 μM. This sensor system shows great potential application for dopamine detection in dopamine drug samples and for future easy-to-make analytical devices.

  9. Increased brain dopamine and dopamine receptors in schizophrenia

    International Nuclear Information System (INIS)

    Mackay, A.V.; Iversen, L.L.; Rossor, M.; Spokes, E.; Bird, E.; Arregui, A.; Creese, I.; Synder, S.H.

    1982-01-01

    In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients

  10. Peripheral Dopamine in Restless Legs Syndrome

    Directory of Open Access Journals (Sweden)

    Ulrike H. Mitchell

    2018-03-01

    Full Text Available Objective/BackgroundRestless Legs Syndrome (RLS is a dopamine-dependent disorder characterized by a strong urge to move. The objective of this study was to evalulate blood levels of dopamine and other catecholamines and blood D2-subtype dopamine receptors (D2Rs in RLS.Patients/MethodsDopamine levels in blood samples from age-matched unmedicated RLS subjects, medicated RLS subjects and Controls were evaluated with high performance liquid chromatography and dopamine D2R white blood cell (WBC expression levels were determined with fluorescence-activated cell sorting and immunocytochemistry.ResultsBlood plasma dopamine levels, but not norepinepherine or epinephrine levels, were significantly increased in medicated RLS subjects vs unmedicated RLS subjects and Controls. The percentage of lymphocytes and monocytes expressing D2Rs differed between Control, RLS medicated and RLS unmedicated subjects. Total D2R expression in lymphocytes, but not monocytes, differed between Control, RLS medicated and RLS unmedicated subjects. D2Rs in lymphocytes, but not monocytes, were sensitive to dopamine in Controls only.ConclusionDownregulation of WBCs D2Rs occurs in RLS. This downregulation is not reversed by medication, although commonly used RLS medications increase plasma dopamine levels. The insensitivity of monocytes to dopamine levels, but their downregulation in RLS, may reflect their utility as a biomarker for RLS and perhaps brain dopamine homeostasis.

  11. Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction.

    Science.gov (United States)

    Cadoni, Cristina

    2016-01-01

    Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant

  12. Fischer 344 and Lewis rat strains as a model of genetic vulnerability to drug addiction

    Directory of Open Access Journals (Sweden)

    Cristina eCadoni

    2016-02-01

    Full Text Available Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60 % of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to