WorldWideScience

Sample records for circuitry regulating rapid

  1. Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders.

    Science.gov (United States)

    Wilcox, Claire E; Pommy, Jessica M; Adinoff, Bryon

    2016-04-01

    Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders

  2. Corticostriatal circuitry in regulating diseases characterized by intrusive thinking

    OpenAIRE

    Kalivas, Benjamin C.; Kalivas, Peter W.

    2016-01-01

    Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumben...

  3. PirB regulates asymmetries in hippocampal circuitry.

    Directory of Open Access Journals (Sweden)

    Hikari Ukai

    Full Text Available Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B. By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB, an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.

  4. Corticostriatal circuitry in regulating diseases characterized by intrusive thinking.

    Science.gov (United States)

    Kalivas, Benjamin C; Kalivas, Peter W

    2016-03-01

    Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

  5. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    McKenna, Dillon; Peever, John

    2017-05-01

    During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and

  6. Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Elisa M. Nabel

    2013-11-01

    Full Text Available Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development –the preeminent model of experience-dependent critical period plasticity- actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins– endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  7. Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

    Science.gov (United States)

    Gee, Dylan G.

    2016-01-01

    Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

  8. Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity.

    Science.gov (United States)

    Vucetic, Zivjena; Reyes, Teresa M

    2010-01-01

    Prevalence of obesity in the general population has increased in the past 15 years from 15% to 35%. With increasing obesity, the coincident medical and social consequences are becoming more alarming. Control over food intake is crucial for the maintenance of body weight and represents an important target for the treatment of obesity. Central nervous system mechanisms responsible for control of food intake have evolved to sense the nutrient and energy levels in the organism and to coordinate appropriate responses to adjust energy intake and expenditure. This homeostatic system is crucial for maintenance of stable body weight over long periods of time of uneven energy availability. However, not only the caloric and nutritional value of food but also hedonic and emotional aspects of feeding affect food intake. In modern society, the increased availability of highly palatable and rewarding (fat, sweet) food can significantly affect homeostatic balance, resulting in dysregulated food intake. This review will focus on the role of hypothalamic and mesolimbic/mesocortical dopaminergic (DA) circuitry in coding homeostatic and hedonic signals for the regulation of food intake and maintenance of caloric balance. The interaction of dopamine with peripheral and central indices of nutritional status (e.g., leptin, ghrelin, neuropeptide Y), and the susceptibility of the dopamine system to prenatal insults will be discussed. Additionally, the importance of alterations in dopamine signaling that occur coincidently with obesity will be addressed.

  9. Role of basal ganglia in sleep-wake regulation: neural circuitry and clinical significance

    Directory of Open Access Journals (Sweden)

    Ramalingam Vetrivelan

    2010-11-01

    Full Text Available Researchers over the last decade have made substantial progress towards understanding the roles of dopamine and the basal ganglia in the control of sleep-wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the basal ganglia (BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson’s disease in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine and modafinil may be linked to the ventral periaquductal grey (vPAG dopaminergic circuitry targeting the extra-BG sleep-wake network.

  10. Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise.

    Directory of Open Access Journals (Sweden)

    Antoine Lutz

    2008-03-01

    Full Text Available Recent brain imaging studies using functional magnetic resonance imaging (fMRI have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices during meditation (versus rest. During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ, and right posterior superior temporal sulcus (pSTS in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in

  11. Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

    Directory of Open Access Journals (Sweden)

    Christelle Anaclet

    2010-01-01

    Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle

  12. Baseline Levels of Rapid Eye Movement Sleep May Protect Against Excessive Activity in Fear-Related Neural Circuitry.

    Science.gov (United States)

    Lerner, Itamar; Lupkin, Shira M; Sinha, Neha; Tsai, Alan; Gluck, Mark A

    2017-11-15

    Sleep, and particularly rapid eye movement sleep (REM), has been implicated in the modulation of neural activity following fear conditioning and extinction in both human and animal studies. It has long been presumed that such effects play a role in the formation and persistence of posttraumatic stress disorder, of which sleep impairments are a core feature. However, to date, few studies have thoroughly examined the potential effects of sleep prior to conditioning on subsequent acquisition of fear learning in humans. Furthermore, these studies have been restricted to analyzing the effects of a single night of sleep-thus assuming a state-like relationship between the two. In the current study, we used long-term mobile sleep monitoring and functional neuroimaging (fMRI) to explore whether trait-like variations in sleep patterns, measured in advance in both male and female participants, predict subsequent patterns of neural activity during fear learning. Our results indicate that higher baseline levels of REM sleep predict reduced fear-related activity in, and connectivity between, the hippocampus, amygdala and ventromedial PFC during conditioning. Additionally, skin conductance responses (SCRs) were weakly correlated to the activity in the amygdala. Conversely, there was no direct correlation between REM sleep and SCRs, indicating that REM may only modulate fear acquisition indirectly. In a follow-up experiment, we show that these results are replicable, though to a lesser extent, when measuring sleep over a single night just before conditioning. As such, baseline sleep parameters may be able to serve as biomarkers for resilience, or lack thereof, to trauma. SIGNIFICANCE STATEMENT Numerous studies over the past two decades have established a clear role of sleep in fear-learning processes. However, previous work has focused on the effects of sleep following fear acquisition, thus neglecting the potential effects of baseline sleep levels on the acquisition itself. The

  13. An Exponential Regulator for Rapidity Divergences

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ye [Fermilab; Neill, Duff [MIT, Cambridge, CTP; Zhu, Hua Xing [MIT, Cambridge, CTP

    2016-04-01

    Finding an efficient and compelling regularization of soft and collinear degrees of freedom at the same invariant mass scale, but separated in rapidity is a persistent problem in high-energy factorization. In the course of a calculation, one encounters divergences unregulated by dimensional regularization, often called rapidity divergences. Once regulated, a general framework exists for their renormalization, the rapidity renormalization group (RRG), leading to fully resummed calculations of transverse momentum (to the jet axis) sensitive quantities. We examine how this regularization can be implemented via a multi-differential factorization of the soft-collinear phase-space, leading to an (in principle) alternative non-perturbative regularization of rapidity divergences. As an example, we examine the fully-differential factorization of a color singlet's momentum spectrum in a hadron-hadron collision at threshold. We show how this factorization acts as a mother theory to both traditional threshold and transverse momentum resummation, recovering the classical results for both resummations. Examining the refactorization of the transverse momentum beam functions in the threshold region, we show that one can directly calculate the rapidity renormalized function, while shedding light on the structure of joint resummation. Finally, we show how using modern bootstrap techniques, the transverse momentum spectrum is determined by an expansion about the threshold factorization, leading to a viable higher loop scheme for calculating the relevant anomalous dimensions for the transverse momentum spectrum.

  14. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  15. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.

    Directory of Open Access Journals (Sweden)

    Shantelle L LaFayette

    2010-08-01

    Full Text Available Fungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC, which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which

  16. NPR-9, a Galanin-Like G-Protein Coupled Receptor, and GLR-1 Regulate Interneuronal Circuitry Underlying Multisensory Integration of Environmental Cues in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jason C Campbell

    2016-05-01

    Full Text Available C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson's, Alzheimer's, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration

  17. Reward Circuitry in Addiction.

    Science.gov (United States)

    Cooper, Sarah; Robison, A J; Mazei-Robison, Michelle S

    2017-07-01

    Understanding the brain circuitry that underlies reward is critical to improve treatment for many common health issues, including obesity, depression, and addiction. Here we focus on insights into the organization and function of reward circuitry and its synaptic and structural adaptations in response to cocaine exposure. While the importance of certain circuits, such as the mesocorticolimbic dopamine pathway, are well established in drug reward, recent studies using genetics-based tools have revealed functional changes throughout the reward circuitry that contribute to different facets of addiction, such as relapse and craving. The ability to observe and manipulate neuronal activity within specific cell types and circuits has led to new insight into not only the basic connections between brain regions, but also the molecular changes within these specific microcircuits, such as neurotrophic factor and GTPase signaling or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse. Excitingly, these insights from preclinical rodent work are now being translated into the clinic, where transcranial magnetic simulation and deep brain stimulation therapies are being piloted in human cocaine dependence. Thus, this review seeks to summarize current understanding of the major brain regions implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these regions, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

  18. Rapid and reversible epigenome editing by endogenous chromatin regulators.

    Science.gov (United States)

    Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

    2017-09-15

    Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

  19. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

    Science.gov (United States)

    Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

    2014-06-16

    Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Strengthening health professions regulation in Cambodia: a rapid assessment.

    Science.gov (United States)

    Clarke, David; Duke, Jan; Wuliji, Tana; Smith, Alyson; Phuong, Keat; San, Un

    2016-03-10

    This paper describes a rapid assessment of Cambodia's current system for regulating its health professions. The assessment forms part of a co-design process to set strategic priorities for strengthening health profession regulation to improve the quality and safety of health services. A health system approach for strengthening health professions' regulation is underway and aims to support the Government of Cambodia's plans for scaling up its health workforce, improving health services' safety and quality, and meeting its Association of South East Asian Nations (ASEAN) obligations to facilitate trade in health care services. The assessment used a mixed methods approach including: A desktop review of key laws, plans, reports and other documents relating to the regulation of the health professions in Cambodia (medicine, dentistry, midwifery, nursing and pharmacy); Key informant interviews with stakeholders in Cambodia (The term "stakeholders" refers to government officials, people working on health professional regulation, people working for the various health worker training institutions and health workers at the national and provincial level); Surveys and questionnaires to assess Cambodian stakeholder knowledge of regulation; Self-assessments by members of the five Cambodian regulatory councils regarding key capacities and activities of high-performing regulatory bodies; and A rapid literature review to identify: The key functions of health professional regulation; The key issues affecting the Cambodian health sector (including relevant developments in the wider ASEAN region); and "Smart" health profession regulation practices of possible relevance to Cambodia. We found that the current regulatory system only partially meets Cambodia's needs. A number of key regulatory functions are being performed, but overall, the current system was not designed with Cambodia's specific needs in mind. The existing system is also overly complex, with considerable duplication and

  1. Innovation in regulation of rapidly changing health markets.

    Science.gov (United States)

    Bloom, Gerald; Henson, Spencer; Peters, David H

    2014-06-24

    The rapid evolution and spread of health markets across low and middle-income countries (LMICs) has contributed to a significant increase in the availability of health-related goods and services around the world. The support institutions needed to regulate these markets have lagged behind, with regulatory systems that are weak and under-resourced. This paper explores the key issues associated with regulation of health markets in LMICs, and the different goals of regulation, namely quality and safety of care, value for money, social agreement over fair access and financing, and accountability. Licensing, price controls, and other traditional approaches to the regulation of markets for health products and services have played an important role, but they have been of questionable effectiveness in ensuring safety and efficacy at the point of the user in LMICs. The paper proposes a health market systems conceptual framework, using the value chain for the production, distribution and retail of health goods and services, to examine regulation of health markets in the LMIC context. We conclude by exploring the changing context going forwards, laying out implications for future heath market regulation. We argue that the case for new approaches to the regulation of markets for health products and services in LMICs is compelling. Although traditional "command and control" approaches will have a place in the toolkit of regulators, a broader bundle of approaches is needed that is adapted to the national and market-level context of particular LMICs. The implication is that it is not possible to apply standard or single interventions across countries, as approaches proven to work well in one context will not necessarily work well elsewhere.

  2. Synaptic plasticity in drug reward circuitry.

    Science.gov (United States)

    Winder, Danny G; Egli, Regula E; Schramm, Nicole L; Matthews, Robert T

    2002-11-01

    Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

  3. Chemical regulation on fire: rapid policy advances on flame retardants.

    Science.gov (United States)

    Cordner, Alissa; Mulcahy, Margaret; Brown, Phil

    2013-07-02

    Chemicals that are widely used in consumer products offer challenges to product manufacturers, risk managers, environmental regulators, environmental scientists, and the interested public. However, the factors that cause specific chemicals to rise to the level of regulatory, scientific, and social movement concern and scrutiny are not well documented, and scientists are frequently unclear about exactly how their research impacts policy. Through a case study of advocacy around flame retardant chemicals, this paper traces the pathways through which scientific evidence and concern is marshaled by both advocacy groups and media sources to affect policy change. We focus our analysis around a broad coalition of environmental and public health advocacy organizations and an investigative journalism series published in 2012 in the Chicago Tribune. We demonstrate that the Tribune series both brought the issue to a wider public audience and precipitated government action, including state policy revisions and federal Senate hearings. We also show how a broad and successful flame retardant coalition developed, leveraged a media event, and influenced policy at multiple institutional levels. The analysis draws on over 110 in-depth interviews, literature and Web site reviews, and observations at a flame retardant manufacturing company, government offices, and scientific and advocacy conferences.

  4. Lighting up the brain's reward circuitry.

    Science.gov (United States)

    Lobo, Mary Kay

    2012-07-01

    The brain's reward circuit is critical for mediating natural reward behaviors including food, sex, and social interaction. Drugs of abuse take over this circuit and produce persistent molecular and cellular alterations in the brain regions and their neural circuitry that make up the reward pathway. Recent use of optogenetic technologies has provided novel insights into the functional and molecular role of the circuitry and cell subtypes within these circuits that constitute this pathway. This perspective will address the current and future use of light-activated proteins, including those involved in modulating neuronal activity, cellular signaling, and molecular properties in the neural circuitry mediating rewarding stimuli and maladaptive responses to drugs of abuse. © 2012 New York Academy of Sciences.

  5. Signal conditioning circuitry design for instrumentation systems.

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Cory A.

    2012-01-01

    This report details the current progress in the design, implementation, and validation of the signal conditioning circuitry used in a measurement instrumentation system. The purpose of this text is to document the current progress of a particular design in signal conditioning circuitry in an instrumentation system. The input of the signal conditioning circuitry comes from a piezoresistive transducer and the output will be fed to a 250 ksps, 12-bit analog-to-digital converter (ADC) with an input range of 0-5 V. It is assumed that the maximum differential voltage amplitude input from the sensor is 20 mV with an unknown, but presumably high, sensor bandwidth. This text focuses on a specific design; however, the theory is presented in such a way that this text can be used as a basis for future designs.

  6. Packaging and interconnection for superconductive circuitry

    International Nuclear Information System (INIS)

    Anacker, W.

    1976-01-01

    A three dimensional microelectronic module packaged for reduced signal propagation delay times including a plurality of circuit carrying means, which may comprise unbacked chips, with integrated superconductive circuitry thereon is described. The circuit carrying means are supported on their edges and have contact lands in the vicinity of, or at, the edges to provide for interconnecting circuitry. The circuit carrying means are supported by supporting means which include slots to provide a path for interconnection wiring to contact the lands of the circuit carrying means. Further interconnecting wiring may take the form of integrated circuit wiring on the reverse side of the supporting means. The low heat dissipation of the superconductive circuitry allows the circuit carrying means to be spaced approximately no less than 30 mils apart. The three dimensional arrangement provides lower random propagation delays than would a planar array of circuits

  7. Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo

    DEFF Research Database (Denmark)

    Nudelman, Aaron Samuel; DiRocco, Derek P; Lambert, Talley J

    2010-01-01

    Activity-dependent changes in gene-expression are believed to underlie the molecular representation of memory. In this study, we report that in vivo activation of neurons rapidly induces the CREB-regulated microRNA miR-132. To determine if production of miR-132 is regulated by neuronal activity its......, olfactory bulb, and striatum by contextual fear conditioning, odor-exposure, and cocaine-injection, respectively, also increased pri-miR-132. Induction kinetics of pri-miR-132 were monitored and found to parallel those of immediate early genes, peaking at 45 min and returning to basal levels within 2 h...

  8. Rapid male-specific regulatory divergence and down regulation of spermatogenesis genes in Drosophila species hybrids.

    Directory of Open Access Journals (Sweden)

    Jennifer Ferguson

    Full Text Available In most crosses between closely related species of Drosophila, the male hybrids are sterile and show postmeiotic abnormalities. A series of gene expression studies using genomic approaches have found significant down regulation of postmeiotic spermatogenesis genes in sterile male hybrids. These results have led some to suggest a direct relationship between down regulation in gene expression and hybrid sterility. An alternative explanation to a cause-and-effect relationship between misregulation of gene expression and male sterility is rapid divergence of male sex regulatory elements leading to incompatible interactions in an interspecies hybrid genome. To test the effect of regulatory divergence in spermatogenesis gene expression, we isolated 35 fertile D. simulans strains with D. mauritiana introgressions in either the X, second or third chromosome. We analyzed gene expression in these fertile hybrid strains for a subset of spermatogenesis genes previously reported as significantly under expressed in sterile hybrids relative to D. simulans. We found that fertile autosomal introgressions can cause levels of gene down regulation similar to that of sterile hybrids. We also found that X chromosome heterospecific introgressions cause significantly less gene down regulation than autosomal introgressions. Our results provide evidence that rapid male sex gene regulatory divergence can explain misexpression of spermatogenesis genes in hybrids.

  9. Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation.

    Science.gov (United States)

    Li, Congxin; Cesbron, François; Oehler, Michael; Brunner, Michael; Höfer, Thomas

    2018-04-25

    Gene regulation is a complex non-equilibrium process. Here, we show that quantitating the temporal regulation of key gene states (transcriptionally inactive, active, and refractory) provides a parsimonious framework for analyzing gene regulation. Our theory makes two non-intuitive predictions. First, for transcription factors (TFs) that regulate transcription burst frequency, as opposed to amplitude or duration, weak TF binding is sufficient to elicit strong transcriptional responses. Second, refractoriness of a gene after a transcription burst enables rapid responses to stimuli. We validate both predictions experimentally by exploiting the natural, optogenetic-like responsiveness of the Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we demonstrate that differential regulation of WCC target genes is caused by different gene activation rates, not different TF occupancy, and that these rates are tuned by both the core promoter and the distance between TF-binding site and core promoter. In total, our work demonstrates the relevance of a kinetic, non-equilibrium framework for understanding transcriptional regulation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A review of visual perception mechanisms that regulate rapid adaptive camouflage in cuttlefish.

    Science.gov (United States)

    Chiao, Chuan-Chin; Chubb, Charles; Hanlon, Roger T

    2015-09-01

    We review recent research on the visual mechanisms of rapid adaptive camouflage in cuttlefish. These neurophysiologically complex marine invertebrates can camouflage themselves against almost any background, yet their ability to quickly (0.5-2 s) alter their body patterns on different visual backgrounds poses a vexing challenge: how to pick the correct body pattern amongst their repertoire. The ability of cuttlefish to change appropriately requires a visual system that can rapidly assess complex visual scenes and produce the motor responses-the neurally controlled body patterns-that achieve camouflage. Using specifically designed visual backgrounds and assessing the corresponding body patterns quantitatively, we and others have uncovered several aspects of scene variation that are important in regulating cuttlefish patterning responses. These include spatial scale of background pattern, background intensity, background contrast, object edge properties, object contrast polarity, object depth, and the presence of 3D objects. Moreover, arm postures and skin papillae are also regulated visually for additional aspects of concealment. By integrating these visual cues, cuttlefish are able to rapidly select appropriate body patterns for concealment throughout diverse natural environments. This sensorimotor approach of studying cuttlefish camouflage thus provides unique insights into the mechanisms of visual perception in an invertebrate image-forming eye.

  11. Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation.

    Science.gov (United States)

    Asmussen, Niels; Lin, Zhao; McClure, Michael J; Schwartz, Zvi; Boyan, Barbara D

    2017-12-09

    Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH) 2 D 3 ] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH) 2 D 3 ] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH) 2 D 3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs. Copyright © 2017. Published by Elsevier Inc.

  12. The Development of Micromachined Gyroscope Structure and Circuitry Technology

    Directory of Open Access Journals (Sweden)

    Dunzhu Xia

    2014-01-01

    Full Text Available This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs, piezoelectric vibrating gyroscopes (PVGs, surface acoustic wave (SAW gyroscopes, bulk acoustic wave (BAW gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs, magnetically suspended gyroscopes (MSGs, micro fiber optic gyroscopes (MFOGs, micro fluid gyroscopes (MFGs, micro atom gyroscopes (MAGs, and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

  13. Functional Maps of Neocortical Local Circuitry

    Science.gov (United States)

    Thomson, Alex M.; Lamy, Christophe

    2007-01-01

    This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided. This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized. PMID:18982117

  14. Rapid improvements in emotion regulation predict intensive treatment outcome for patients with bulimia nervosa and purging disorder.

    Science.gov (United States)

    MacDonald, Danielle E; Trottier, Kathryn; Olmsted, Marion P

    2017-10-01

    Rapid and substantial behavior change (RSBC) early in cognitive behavior therapy (CBT) for eating disorders is the strongest known predictor of treatment outcome. Rapid change in other clinically relevant variables may also be important. This study examined whether rapid change in emotion regulation predicted treatment outcomes, beyond the effects of RSBC. Participants were diagnosed with bulimia nervosa or purging disorder (N = 104) and completed ≥6 weeks of CBT-based intensive treatment. Hierarchical regression models were used to test whether rapid change in emotion regulation variables predicted posttreatment outcomes, defined in three ways: (a) binge/purge abstinence; (b) cognitive eating disorder psychopathology; and (c) depression symptoms. Baseline psychopathology and emotion regulation difficulties and RSBC were controlled for. After controlling for baseline variables and RSBC, rapid improvement in access to emotion regulation strategies made significant unique contributions to the prediction of posttreatment binge/purge abstinence, cognitive psychopathology of eating disorders, and depression symptoms. Individuals with eating disorders who rapidly improve their belief that they can effectively modulate negative emotions are more likely to achieve a variety of good treatment outcomes. This supports the formal inclusion of emotion regulation skills early in CBT, and encouraging patient beliefs that these strategies are helpful. © 2017 Wiley Periodicals, Inc.

  15. β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels.

    Science.gov (United States)

    Chen, Chuck T; Bazinet, Richard P

    2015-01-01

    The brain has a unique polyunsaturated fatty acid composition, with high levels of arachidonic and docosahexaenoic acids (DHA) while levels of eicosapentaenoic acid (EPA) are several orders of magnitude lower. As evidence accumulated that fatty acid entry into the brain was not selective and, in fact, that DHA and EPA enter the brain at similar rates, new mechanisms were required to explain their large concentration differences in the brain. Here we summarize recent research demonstrating that EPA is rapidly and extensively β-oxidized upon entry into the brain. Although the ATP generated from the β-oxidation of EPA is low compared to the use of glucose, fatty acid β-oxidation may serve to regulate brain fatty acid levels in the absence of selective transportation. Furthermore, when β-oxidation of EPA is blocked, desaturation of EPA increases and Land׳s recycling decreases to maintain low EPA levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Balancing BEC and IAQ in civil buildings during rapid urbanization in China: Regulation, interplay and collaboration

    International Nuclear Information System (INIS)

    Zhang Jiefeng; Bai Zhipeng; Chang, Victor W.C.; Ding Xiao

    2011-01-01

    Energy consumption by building sector becomes more and more important in a rapid growing economy like China. Tremendous efforts have been made on building energy conservation (BEC) to comply with the national energy-saving policies over the last three decades. At the same time, with the increasing awareness of the importance of indoor air quality (IAQ), Ministry of Health (MoH) also initiates the related standards to fulfill the needs. BEC and IAQ are two main concerns in the current building management practice. This paper makes an attempt, based on the regulations and standards in chronological order, to elaborate the followings: (1) the development history of BEC and IAQ management in civil buildings in China, (2) the interplay and sometimes seeming conflicts of BEC and IAQ management in the real practice, (3) the importance of proper communications between related authorities in setting up cross-linked regulations to ensure the success of better building managements. - Highlights: → The development of BEC and IAQ management follow similar timelines. → Misconducts of building management practice may lead to compromised IAQ. → Ventilation design and thermal insulation have impacts on both BEC and IAQ. → Proper cross-agency communications essentially promote the BEC and IAQ management.

  17. Singing modulates parvalbumin interneurons throughout songbird forebrain vocal control circuitry

    Science.gov (United States)

    Zengin-Toktas, Yildiz

    2017-01-01

    Across species, the performance of vocal signals can be modulated by the social environment. Zebra finches, for example, adjust their song performance when singing to females (‘female-directed’ or FD song) compared to when singing in isolation (‘undirected’ or UD song). These changes are salient, as females prefer the FD song over the UD song. Despite the importance of these performance changes, the neural mechanisms underlying this social modulation remain poorly understood. Previous work in finches has established that expression of the immediate early gene EGR1 is increased during singing and modulated by social context within the vocal control circuitry. Here, we examined whether particular neural subpopulations within those vocal control regions exhibit similar modulations of EGR1 expression. We compared EGR1 expression in neurons expressing parvalbumin (PV), a calcium buffer that modulates network plasticity and homeostasis, among males that performed FD song, males that produced UD song, or males that did not sing. We found that, overall, singing but not social context significantly affected EGR1 expression in PV neurons throughout the vocal control nuclei. We observed differences in EGR1 expression between two classes of PV interneurons in the basal ganglia nucleus Area X. Additionally, we found that singing altered the amount of PV expression in neurons in HVC and Area X and that distinct PV interneuron types in Area X exhibited different patterns of modulation by singing. These data indicate that throughout the vocal control circuitry the singing-related regulation of EGR1 expression in PV neurons may be less influenced by social context than in other neuron types and raise the possibility of cell-type specific differences in plasticity and calcium buffering. PMID:28235074

  18. Serotonergic Regulation of Prefrontal Cortical Circuitries Involved in Cognitive Processing: A Review of Individual 5-HT Receptor Mechanisms and Concerted Effects of 5-HT Receptors Exemplified by the Multimodal Antidepressant Vortioxetine.

    Science.gov (United States)

    Leiser, Steven C; Li, Yan; Pehrson, Alan L; Dale, Elena; Smagin, Gennady; Sanchez, Connie

    2015-07-15

    It has been known for several decades that serotonergic neurotransmission is a key regulator of cognitive function, mood, and sleep. Yet with the relatively recent discoveries of novel serotonin (5-HT) receptor subtypes, as well as an expanding knowledge of their expression level in certain brain regions and localization on certain cell types, their involvement in cognitive processes is still emerging. Of particular interest are cognitive processes impacted in neuropsychiatric and neurodegenerative disorders. The prefrontal cortex (PFC) is critical to normal cognitive processes, including attention, impulsivity, planning, decision-making, working memory, and learning or recall of learned memories. Furthermore, serotonergic dysregulation within the PFC is implicated in many neuropsychiatric disorders associated with prominent symptoms of cognitive dysfunction. Thus, it is important to better understand the overall makeup of serotonergic receptors in the PFC and on which cell types these receptors mediate their actions. In this Review, we focus on 5-HT receptor expression patterns within the PFC and how they influence cognitive behavior and neurotransmission. We further discuss the net effects of vortioxetine, an antidepressant acting through multiple serotonergic targets given the recent findings that vortioxetine improves cognition by modulating multiple neurotransmitter systems.

  19. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

    2013-11-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  20. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    International Nuclear Information System (INIS)

    Chen, Shiwei; Dong, Yushu; Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng; Hou, Wugang; Li, Wei

    2013-01-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury

  1. How plastic are human spinal cord motor circuitries?

    DEFF Research Database (Denmark)

    Christiansen, Lasse; Lundbye-Jensen, Jesper; Perez, Monica A

    2017-01-01

    Human and animal studies have documented that neural circuitries in the spinal cord show adaptive changes caused by altered supraspinal and/or afferent input to the spinal circuitry in relation to learning, immobilization, injury and neurorehabilitation. Reversible adaptations following, e.g. the...

  2. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation

    Science.gov (United States)

    Mackey, Tim K.

    2016-01-01

    The adoption and use of digital forms of direct-to-consumer advertising (also known as "eDTCA") is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA) notices of violations (NOVs) and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the "disruptive" qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored. PMID:27239871

  3. Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes

    Directory of Open Access Journals (Sweden)

    Lane Robert P

    2007-09-01

    Full Text Available Abstract The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system.

  4. Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

    Science.gov (United States)

    Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

    2010-01-01

    Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507

  5. Disrupted Working Memory Circuitry in Adolescent Psychosis

    Directory of Open Access Journals (Sweden)

    Ariel Eckfeld

    2017-08-01

    Full Text Available Individuals with schizophrenia (SZ consistently show deficits in spatial working memory (WM and associated atypical patterns of neural activity within key WM regions, including the dorsolateral prefrontal cortex (dlPFC and parietal cortices. However, little research has focused on adolescent psychosis (AP and potential age-associated disruptions of WM circuitry that may occur in youth with this severe form of illness. Here we utilized each subject’s individual spatial WM capacity to investigate task-based neural dysfunction in 17 patients with AP (16.58 ± 2.60 years old as compared to 17 typically developing, demographically comparable adolescents (18.07 ± 3.26 years old. AP patients showed lower behavioral performance at higher WM loads and lower overall WM capacity compared to healthy controls. Whole-brain activation analyses revealed greater bilateral precentral and right postcentral activity in controls relative to AP patients, when controlling for individual WM capacity. Seed-based psychophysiological interaction (PPI analyses revealed significantly greater co-activation between the left dlPFC and left frontal pole in controls relative to AP patients. Significant group-by-age interactions were observed in both whole-brain and PPI analyses, with AP patients showing atypically greater neural activity and stronger coupling between WM task activated brain regions as a function of increasing age. Additionally, AP patients demonstrated positive relationships between right dlPFC neural activity and task performance, but unlike healthy controls, failed to show associations between neural activity and out-of-scanner neurocognitive performance. Collectively, these findings are consistent with atypical WM-related functioning and disrupted developmental processes in youth with AP.

  6. Circuitry for use with an ionizing-radiation detector

    International Nuclear Information System (INIS)

    Marshall, J.H. III; Harrington, T.M.

    1976-01-01

    An improved system of circuitry for use in combination with an ionizing-radiation detector over a wide range of radiation levels includes a current-to-frequency converter together with a digital data processor for respectively producing and measuring a pulse repetition frequency which is proportional to the output current of the ionizing-radiation detector, a dc-to-dc converter for providing closely regulated operating voltages from a rechargeable battery and a bias supply for providing high voltage to the ionization chamber. The ionizing-radiation detector operating as a part of this system produces a signal responsive to the level of ionizing radiation in the vicinity of the detector, and this signal is converted into a pulse frequency which will vary in direct proportion to such level of ionizing-radiation. The data processor, by counting the number of pulses from the converter over a selected integration interval, provides a digital indication of radiation dose rate, and by accumulating the total of all such pulses provides a digital indication of total integrated dose. Ordinary frequency-to-voltage conversion devices or digital display techniques can be used as a means for providing audible and visible indications of dose and dose-rate levels

  7. Nanocantilever based mass sensor integrated with cmos circuitry

    DEFF Research Database (Denmark)

    Davis, Zachary James; Abadal, G.; Campabadal, F.

    2003-01-01

    We have demonstrated the successful integration of a cantilever based mass detector with standard CMOS circuitry. The purpose of the circuitry is to facilitate the readout of the cantilever's deflection in order to measure resonant frequency shifts of the cantilever. The principle and design...... of the mass detector are presented showing that miniaturization of such cantilever based resonant devices leads to highly sensitive mass sensors, which have the potential to detect single molecules. The design of the readout circuitry used for the first electrical characterization of an integrated cantilever...... with CMOS circuitry is demonstrated. The electrical characterization of the device shows that the resonant behavior of the cantilever depends on the applied voltages, which corresponds to theory....

  8. Transitional circuitry for studying the properties of DNA

    Science.gov (United States)

    Trubochkina, N.

    2018-01-01

    The article is devoted to a new view of the structure of DNA as an intellectual scheme possessing the properties of logic and memory. The theory of transient circuitry, developed by the author for optimal computer circuits, revealed an amazing structural similarity between mathematical models of transition silicon elements and logic and memory circuits of solid state transient circuitry and atomic models of parts of DNA.

  9. Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification

    KAUST Repository

    Li, Lixin; Piatek, Marek J.; Atef, Ahmed; Piatek, Agnieszka Anna; Wibowo, Anjar Tri; Fang, Xiaoyun; Sabir, Jamal Sabir M; Zhu, Jiankang; Mahfouz, Magdy M.

    2012-01-01

    dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach

  10. Circuitry linking the Csr and stringent response global regulatory systems.

    Science.gov (United States)

    Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-06-01

    CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

  11. A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry

    Science.gov (United States)

    Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

    2013-01-01

    Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

  12. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

    Directory of Open Access Journals (Sweden)

    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  13. Rapid transporter regulation prevents substrate flow traffic jams in boron transport

    Science.gov (United States)

    Sotta, Naoyuki; Duncan, Susan; Tanaka, Mayuki; Sato, Takafumi

    2017-01-01

    Nutrient uptake by roots often involves substrate-dependent regulated nutrient transporters. For robust uptake, the system requires a regulatory circuit within cells and a collective, coordinated behaviour across the tissue. A paradigm for such systems is boron uptake, known for its directional transport and homeostasis, as boron is essential for plant growth but toxic at high concentrations. In Arabidopsis thaliana, boron uptake occurs via diffusion facilitators (NIPs) and exporters (BORs), each presenting distinct polarity. Intriguingly, although boron soil concentrations are homogenous and stable, both transporters manifest strikingly swift boron-dependent regulation. Through mathematical modelling, we demonstrate that slower regulation of these transporters leads to physiologically detrimental oscillatory behaviour. Cells become periodically exposed to potentially cytotoxic boron levels, and nutrient throughput to the xylem becomes hampered. We conclude that, while maintaining homeostasis, swift transporter regulation within a polarised tissue context is critical to prevent intrinsic traffic-jam like behaviour of nutrient flow. PMID:28870285

  14. Role of norepinephrine in the regulation of rapid eye movement sleep

    Indian Academy of Sciences (India)

    Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified ...

  15. Reducing Ripple In A Switching Voltage Regulator

    Science.gov (United States)

    Paulkovich, John; Rodriguez, G. Ernest

    1994-01-01

    Ripple voltage in output of switching voltage regulator reduced substantially by simple additional circuitry adding little to overall weight and size of regulator. Heretofore, additional filtering circuitry needed to obtain comparable reductions in ripple typically as large and heavy as original regulator. Current opposing ripple current injected into filter capacitor.

  16. A potential kidney-bone axis involved in the rapid minute-to-minute regulation of plasma Ca2+

    DEFF Research Database (Denmark)

    Nordholm, Anders; Mace, Maria L; Gravesen, Eva

    2015-01-01

    , as induced by total bilateral nephrectomy and to study the effect of absence of kidneys on the rapid recovery of p-Ca(2+) from a brief induction of acute hypocalcemia. METHODS: The rapid regulation of p-Ca(2+) was examined in sham-operated rats, acute nephrectomized rats (NX), acute thyroparathyrectomized......(TPTX) rats and NX-TPTX rats. RESULTS: The results clearly showed that p-Ca(2+) falls rapidly and significantly very early after acute NX, from 1.23 ± 0.02 to 1.06 ± 0.04 mM (p hypocalcemia was induced by a 30 min iv infusion of EGTA. Control groups had saline. After discontinuing EGTA...... a rapid increase in p-Ca(2+) took place, but with a lower level in NX rats (p effect of accumulation of Calcitonin and C-terminal PTH, both having potential hypocalcemic actions. Acute TPTX resulted in hypercalcemia, 1.44 ± 0.02 mM and less in NX-TPTX rats,1...

  17. Development and aging of human spinal cord circuitries

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Willerslev-Olsen, Maria; Lorentzen, Jakob

    2017-01-01

    development and to what extent they are shaped according to the demands of the body that they control and the environment that the body has to interact with. We also discuss how ageing processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries....... The complex, multi-facetted connectivity of the spinal cord motor circuitries allow that they can be used to generate vastly different movements and that their activity can be adapted to meet new challenges imposed by bodily changes or a changing environment. There are thus plenty of possibilities...

  18. The inappropriate occurrence of rapid eye movement sleep in narcolepsy is not due to a defect in homeostatic regulation of rapid eye movement sleep.

    Science.gov (United States)

    Roman, Alexis; Meftah, Soraya; Arthaud, Sébastien; Luppi, Pierre-Hervé; Peyron, Christelle

    2018-06-01

    Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. The later three symptoms together with a short rapid eye movement (REM) sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates. We first performed 48 hr of REM sleep deprivation using the classic small-platforms-over-water method. We found that narcoleptic mice are similarly REM sleep deprived to WT mice. Although they had shorter sleep latency, Orex-KO mice recovered similarly to WT during the following 10 hr of recovery. Interestingly, Orex-KO mice also had cataplexy episodes immediately after REM sleep deprivation, anticipating REM sleep rebound, at a time of day when cataplexy does not occur in baseline condition. We then evaluated REM sleep propensity using our new automated method of deprivation that performs a specific and efficient REM sleep deprivation. We showed that REM sleep propensity is similar during light phase in Orex-KO and WT mice. However, during the dark phase, REM sleep propensity was not suppressed in Orex-KO mice when hypocretin/orexin neuropeptides are normally released. Altogether our data suggest that in addition to the well-known wake-promoting role of hypocretin/orexin, these neuropeptides would also suppress REM sleep. Therefore, hypocretin/orexin deficiency would facilitate the occurrence of REM sleep at any time of day in an opportunistic manner as seen in human narcolepsy.

  19. Network and neuronal membrane properties in hybrid networks reciprocally regulate selectivity to rapid thalamocortical inputs.

    Science.gov (United States)

    Pesavento, Michael J; Pinto, David J

    2012-11-01

    Rapidly changing environments require rapid processing from sensory inputs. Varying deflection velocities of a rodent's primary facial vibrissa cause varying temporal neuronal activity profiles within the ventral posteromedial thalamic nucleus. Local neuron populations in a single somatosensory layer 4 barrel transform sparsely coded input into a spike count based on the input's temporal profile. We investigate this transformation by creating a barrel-like hybrid network with whole cell recordings of in vitro neurons from a cortical slice preparation, embedding the biological neuron in the simulated network by presenting virtual synaptic conductances via a conductance clamp. Utilizing the hybrid network, we examine the reciprocal network properties (local excitatory and inhibitory synaptic convergence) and neuronal membrane properties (input resistance) by altering the barrel population response to diverse thalamic input. In the presence of local network input, neurons are more selective to thalamic input timing; this arises from strong feedforward inhibition. Strongly inhibitory (damping) network regimes are more selective to timing and less selective to the magnitude of input but require stronger initial input. Input selectivity relies heavily on the different membrane properties of excitatory and inhibitory neurons. When inhibitory and excitatory neurons had identical membrane properties, the sensitivity of in vitro neurons to temporal vs. magnitude features of input was substantially reduced. Increasing the mean leak conductance of the inhibitory cells decreased the network's temporal sensitivity, whereas increasing excitatory leak conductance enhanced magnitude sensitivity. Local network synapses are essential in shaping thalamic input, and differing membrane properties of functional classes reciprocally modulate this effect.

  20. [Industry regulation and its relationship to the rapid marketing of medical devices].

    Science.gov (United States)

    Matsuoka, Atsuko

    2012-01-01

    In the market of medical devices, non-Japanese products hold a large part even in Japan. To overcome this situation, the Japanese government has been announcing policies to encourage the medical devices industry, such as the 5-year strategy for medical innovation (June 6, 2012). The Division of Medical Devices has been contributing to rapid marketing of medical devices by working out the standards for approval review and accreditation of medical devices, guidances on evaluation of medical devices with emerging technology, and test methods for biological safety evaluation of medical devices, as a part of practice in the field of regulatory science. The recent outcomes are 822 standards of accreditation for Class II medical devices, 14 guidances on safety evaluation of medical devices with emerging technology, and the revised test methods for biological safety evaluation (MHLW Notification by Director, OMDE, Yakushokuki-hatsu 0301 No. 20 "Basic Principles of Biological Safety Evaluation Required for Application for Approval to Market Medical Devices").

  1. Reward Circuitry Function in Autism during Face Anticipation and Outcomes

    Science.gov (United States)

    Dichter, Gabriel S.; Richey, J. Anthony; Rittenberg, Alison M.; Sabatino, Antoinette; Bodfish, James W.

    2012-01-01

    The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary…

  2. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  3. The origin of behavioral bursts in decision-making circuitry.

    Directory of Open Access Journals (Sweden)

    Amanda Sorribes

    2011-06-01

    Full Text Available From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switches of wild-type Drosophila are very well described by the Weibull distribution, a common distribution of bursty dynamics in complex systems. The bursty dynamics of wild-type Drosophila walking activity are shown to be determined by this inter-event distribution alone and not by memory effects, thus resembling human dynamics. Further, using mutant flies that disrupt dopaminergic signaling or the mushroom body, circuitry implicated in decision-making, we show that the degree of behavioral burstiness can be modified. These results are thus consistent with the proposed link between decision-making circuitry and bursty dynamics, and highlight the importance of using simple experimental systems to test general theoretical models of behavior. The findings further suggest that analysis of bursts could prove useful for the study and evaluation of decision-making circuitry.

  4. Beneficial Autoimmunity at Body Surfaces – Immune Surveillance and Rapid Type 2 Immunity Regulate Tissue Homeostasis and Cancer

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis. PMID:25101088

  5. Beneficial autoimmunity at body surfaces - immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer.

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress - a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis.

  6. Caenorhabditis elegans Male Copulation Circuitry Incorporates Sex-Shared Defecation Components To Promote Intromission and Sperm Transfer

    Science.gov (United States)

    LeBoeuf, Brigitte; Garcia, L. Rene

    2016-01-01

    Sexual dimorphism can be achieved using a variety of mechanisms, including sex-specific circuits and sex-specific function of shared circuits, though how these work together to produce sexually dimorphic behaviors requires further investigation. Here, we explore how components of the sex-shared defecation circuitry are incorporated into the sex-specific male mating circuitry in Caenorhabditis elegans to produce successful copulation. Using behavioral studies, calcium imaging, and genetic manipulation, we show that aspects of the defecation system are coopted by the male copulatory circuitry to facilitate intromission and ejaculation. Similar to hermaphrodites, male defecation is initiated by an intestinal calcium wave, but circuit activity is coordinated differently during mating. In hermaphrodites, the tail neuron DVB promotes expulsion of gut contents through the release of the neurotransmitter GABA onto the anal depressor muscle. However, in the male, both neuron and muscle take on modified functions to promote successful copulation. Males require calcium-dependent activator protein for secretion (CAPS)/unc-31, a dense core vesicle exocytosis activator protein, in the DVB to regulate copulatory spicule insertion, while the anal depressor is remodeled to promote release of sperm into the hermaphrodite. This work shows how sex-shared circuitry is modified in multiple ways to contribute to sex-specific mating. PMID:28031243

  7. Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex specific manner

    Science.gov (United States)

    Dickens, M.J.; Balthazart, J.; Cornil, C. A.

    2012-01-01

    Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, non-genomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce respectively a rapid inhibition or increase in preoptic aromatase activity (AA). Here, we tested quail that were either non-stressed or acutely stressed (15 min restraint) immediately prior to sexual interaction (5 min) with stressed or non-stressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (behaviour suggesting that the input from the sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: while males did not show any effect of partner status, females responded to both their stress exposure and the male partner’s stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner’s exhibition of sexually aggressive behaviour suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple – sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. In contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner’s stress exposure, and female-directed male behaviour. PMID:22612582

  8. Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification

    KAUST Repository

    Li, Lixin

    2012-01-22

    Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants. © 2012 Springer Science+Business Media B.V.

  9. Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification.

    Science.gov (United States)

    Li, Lixin; Piatek, Marek J; Atef, Ahmed; Piatek, Agnieszka; Wibowo, Anjar; Fang, Xiaoyun; Sabir, J S M; Zhu, Jian-Kang; Mahfouz, Magdy M

    2012-03-01

    Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants.

  10. Rapid regulation of leaf photosynthesis, carbohydrate status and leaf area expansion to maintain growth in irregular light environments

    DEFF Research Database (Denmark)

    Kjær, Katrine Heinsvig

    2012-01-01

    to maintain carbohydrate status and growth in unpredictable light environments. Our recent results show rapid regulation of photosynthesis and leaf carbohydrate status to maintain growth and light interception in dynamic light environments when campanula, rose and chrysanthemum were grown in a cost......-efficient light control system. Plant dry matter production was in all cases linear related to DLI, despite changes in daily light duration and light intensity of supplemental light suggesting that DLI is the main limiting factor for the prediction of production time in optimal temperature conditions. The results......Protected plant productions in northern latitudes rely heavily on supplemental light use to extend the number of light hours during the day. To conserve electricity and lower costs, a low-energy input system use supplemental lights preferable during less expensive off-peak hours and turn lighting...

  11. Low Power/Low Voltage Interface Circuitry for Capacitive Sensors

    DEFF Research Database (Denmark)

    Furst, Claus Efdmann

    This thesis focuses mainly on low power/low voltage interface circuits, implemented in CMOS, for capacitive sensors. A brief discussion of demands and possibilities for analog signal processing in the future is presented. Techniques for low power design is presented. This is done by analyzing power...... power consumption. It is shown that the Sigma-Delta modulator is advantageous when embedded in a feedback loop with a mechanical sensor. Here a micro mechanical capacitive microphone. Feedback and detection circuitry for a capacitive microphone is presented. Practical implementations of low power....../low voltage interface circuitry is presented. It is demonstrated that an amplifier optimized for a capacitive microphone implemented in a standard 0.7 micron CMOS technology competes well with a traditional JFET amplifier. Furthermore a low power/low voltage 3rd order Sigma-Delta modulator is presented...

  12. Two genes with similarity to bacterial response regulators are rapidly and specifically induced by cytokinin in Arabidopsis

    Science.gov (United States)

    Brandstatter, I.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

    1998-01-01

    Cytokinins are central regulators of plant growth and development, but little is known about their mode of action. By using differential display, we identified a gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated within 10 min by the exogenous application of cytokinin, and this induction did not require de novo protein synthesis. IBC6 was not induced by other plant hormones or by light. A second Arabidopsis gene with a sequence highly similar to IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with somewhat slower kinetics and to a lesser extent. The pattern of expression of the two genes was similar, with higher expression in leaves, rachises, and flowers and lower transcript levels in roots and siliques. Sequence analysis revealed that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component response regulators. This homology, coupled with previously published work on the CKI1 histidine kinase homolog, suggests that these proteins may play a role in early cytokinin signaling.

  13. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

    Science.gov (United States)

    Phillips, Mary L; Swartz, Holly A.

    2014-01-01

    Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

  14. Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli.

    Science.gov (United States)

    Pannuri, Archana; Vakulskas, Christopher A; Zere, Tesfalem; McGibbon, Louise C; Edwards, Adrianne N; Georgellis, Dimitris; Babitzke, Paul; Romeo, Tony

    2016-11-01

    Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrC-lacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower

  15. β1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.

    Science.gov (United States)

    Wang, Sen; Xu, Di; Wu, Ting-Ting; Guo, Yan; Chen, Yan-Hong; Zou, Jian-Gang

    2014-05-01

    Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective β1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.

  16. Implementing size-optimal discrete neural networks require analog circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-01

    This paper starts by overviewing results dealing with the approximation capabilities of neural networks, as well as bounds on the size of threshold gate circuits. Based on a constructive solution for Kolmogorov`s superpositions the authors show that implementing Boolean functions can be done using neurons having an identity transfer function. Because in this case the size of the network is minimized, it follows that size-optimal solutions for implementing Boolean functions can be obtained using analog circuitry. Conclusions and several comments on the required precision are ending the paper.

  17. Modeling disease risk through analysis of physical interactions between genetic variants within chromatin regulatory circuitry.

    Science.gov (United States)

    Corradin, Olivia; Cohen, Andrea J; Luppino, Jennifer M; Bayles, Ian M; Schumacher, Fredrick R; Scacheri, Peter C

    2016-11-01

    SNPs associated with disease susceptibility often reside in enhancer clusters, or super-enhancers. Constituents of these enhancer clusters cooperate to regulate target genes and often extend beyond the linkage disequilibrium (LD) blocks containing risk SNPs identified in genome-wide association studies (GWAS). We identified 'outside variants', defined as SNPs in weak LD with GWAS risk SNPs that physically interact with risk SNPs as part of a target gene's regulatory circuitry. These outside variants further explain variation in target gene expression beyond that explained by GWAS-associated SNPs. Additionally, the clinical risk associated with GWAS SNPs is considerably modified by the genotype of outside variants. Collectively, these findings suggest a potential model in which outside variants and GWAS SNPs that physically interact in 3D chromatin collude to influence target transcript levels as well as clinical risk. This model offers an additional hypothesis for the source of missing heritability for complex traits.

  18. Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms.

    Science.gov (United States)

    Nestler, Eric J

    2015-01-01

    Increasing evidence supports an important role for the brain's reward circuitry in controlling mood under normal conditions and contributing importantly to the pathophysiology and symptomatology of a range of mood disorders, such as depression. Here we focus on the nucleus accumbens (NAc), a critical component of the brain's reward circuitry, in depression and other stress-related disorders. The prominence of anhedonia, reduced motivation, and decreased energy level in most individuals with depression supports the involvement of the NAc in these conditions. We concentrate on several transcription factors (CREB, ΔFosB, SRF, NFκB, and β-catenin), which are altered in the NAc in rodent depression models--and in some cases in the NAc of depressed humans, and which produce robust depression- or antidepressant-like effects when manipulated in the NAc in animal models. These studies of the NAc have established novel approaches toward modeling key symptoms of depression in animals and could enable the development of antidepressant medications with fundamentally new mechanisms of action. © 2015 Elsevier Inc. All rights reserved.

  19. DNA-based random number generation in security circuitry.

    Science.gov (United States)

    Gearheart, Christy M; Arazi, Benjamin; Rouchka, Eric C

    2010-06-01

    DNA-based circuit design is an area of research in which traditional silicon-based technologies are replaced by naturally occurring phenomena taken from biochemistry and molecular biology. This research focuses on further developing DNA-based methodologies to mimic digital data manipulation. While exhibiting fundamental principles, this work was done in conjunction with the vision that DNA-based circuitry, when the technology matures, will form the basis for a tamper-proof security module, revolutionizing the meaning and concept of tamper-proofing and possibly preventing it altogether based on accurate scientific observations. A paramount part of such a solution would be self-generation of random numbers. A novel prototype schema employs solid phase synthesis of oligonucleotides for random construction of DNA sequences; temporary storage and retrieval is achieved through plasmid vectors. A discussion of how to evaluate sequence randomness is included, as well as how these techniques are applied to a simulation of the random number generation circuitry. Simulation results show generated sequences successfully pass three selected NIST random number generation tests specified for security applications.

  20. Signal processing circuitry for CMOS-based SAW gas sensors with low power and area

    International Nuclear Information System (INIS)

    Mohd-Yasin, F.; Tye, K.F.; Reaz, M.B.I.

    2009-06-01

    The design and development of interface circuitries for CMOS-based SAW gas sensor is presented in this paper. The SAW gas sensor devices typically run at RF, requiring most designs to have complex signal conditioning circuitry. The proposed approach attempts to design a simple architecture with reduced power consumption. The SAW gas sensors operate at 354MHz. Simulation data show that the interface circuitries are ten times smaller with lower power supply, comparing to existing work. (author)

  1. Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

    Science.gov (United States)

    Yun, Sanghee; Reynolds, Ryan P; Petrof, Iraklis; White, Alicia; Rivera, Phillip D; Segev, Amir; Gibson, Adam D; Suarez, Maiko; DeSalle, Matthew J; Ito, Naoki; Mukherjee, Shibani; Richardson, Devon R; Kang, Catherine E; Ahrens-Nicklas, Rebecca C; Soler, Ivan; Chetkovich, Dane M; Kourrich, Saïd; Coulter, Douglas A; Eisch, Amelia J

    2018-04-16

    Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

  2. Focusing on optic tectum circuitry through the lens of genetics

    Directory of Open Access Journals (Sweden)

    Nevin Linda M

    2010-09-01

    Full Text Available Abstract The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

  3. Silent Synapse-Based Circuitry Remodeling in Drug Addiction.

    Science.gov (United States)

    Dong, Yan

    2016-05-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  4. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  5. Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

    KAUST Repository

    Schmeier, Sebastian; MacPherson, Cameron R; Essack, Magbubah; Kaur, Mandeep; Schaefer, Ulf; Suzuki, Harukazu; Hayashizaki, Yoshihide; Bajic, Vladimir B.

    2009-01-01

    Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

  6. Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

    KAUST Repository

    Schmeier, Sebastian

    2009-12-10

    Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

  7. Mapping the Brain’s Metaphor Circuitry:Is Abstract Thought Metaphorical Thought?

    Directory of Open Access Journals (Sweden)

    George eLakoff

    2014-12-01

    Full Text Available An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry.

  8. Specific interaction between hnRNP H and HPV16 L1 proteins: Implications for late gene auto-regulation enabling rapid viral capsid protein production

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Zi-Zheng; Sun, Yuan-Yuan; Zhao, Min; Huang, Hui [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhang, Jun; Xia, Ning-Shao [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China); Miao, Ji, E-mail: jmiao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhao, Qinjian, E-mail: qinjian_zhao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China)

    2013-01-18

    Highlights: ► The RNA-binding hnRNP H regulates late viral gene expression. ► hnRNP H activity was inhibited by a late viral protein. ► Specific interaction between HPV L1 and hnRNP H was demonstrated. ► Co-localization of HPV L1 and hnRNP H inside cells was observed. ► Viral capsid protein production, enabling rapid capsid assembly, was implicated. -- Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulating the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.

  9. A computational framework for ultrastructural mapping of neural circuitry.

    Directory of Open Access Journals (Sweden)

    James R Anderson

    2009-03-01

    Full Text Available Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM, mosaicking and registration (ir-tools, and large slice viewers (MosaicBuilder, Viking can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina, terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally

  10. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

    Directory of Open Access Journals (Sweden)

    Salvatore Fusco

    2016-02-01

    Full Text Available Summary: Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis. : Using a combination of in vitro and in vivo studies, Fusco et al. find that excess glucose impairs the self-renewal capacity of neural stem cells through a molecular circuit that involves the transcription factor CREB and Sirtuin 1. The authors suggest that this circuitry may link nutrient excess with neurodegeneration and brain aging. Keywords: neural stem cells, adult neurogenesis, CREB, Sirt-1, nutrients, metabolism, diabetes

  11. Epigenetic Regulation of Monocyte and Macrophage Function

    NARCIS (Netherlands)

    Hoeksema, Marten A.; de Winther, Menno P. J.

    2016-01-01

    Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying

  12. Dentate Gyrus circuitry features improve performance of sparse approximation algorithms.

    Directory of Open Access Journals (Sweden)

    Panagiotis C Petrantonakis

    Full Text Available Memory-related activity in the Dentate Gyrus (DG is characterized by sparsity. Memory representations are seen as activated neuronal populations of granule cells, the main encoding cells in DG, which are estimated to engage 2-4% of the total population. This sparsity is assumed to enhance the ability of DG to perform pattern separation, one of the most valuable contributions of DG during memory formation. In this work, we investigate how features of the DG such as its excitatory and inhibitory connectivity diagram can be used to develop theoretical algorithms performing Sparse Approximation, a widely used strategy in the Signal Processing field. Sparse approximation stands for the algorithmic identification of few components from a dictionary that approximate a certain signal. The ability of DG to achieve pattern separation by sparsifing its representations is exploited here to improve the performance of the state of the art sparse approximation algorithm "Iterative Soft Thresholding" (IST by adding new algorithmic features inspired by the DG circuitry. Lateral inhibition of granule cells, either direct or indirect, via mossy cells, is shown to enhance the performance of the IST. Apart from revealing the potential of DG-inspired theoretical algorithms, this work presents new insights regarding the function of particular cell types in the pattern separation task of the DG.

  13. Cost-benefit decision circuitry: proposed modulatory role for acetylcholine.

    Science.gov (United States)

    Fobbs, Wambura C; Mizumori, Sheri J Y

    2014-01-01

    In order to select which action should be taken, an animal must weigh the costs and benefits of possible outcomes associate with each action. Such decisions, called cost-benefit decisions, likely involve several cognitive processes (including memory) and a vast neural circuitry. Rodent models have allowed research to begin to probe the neural basis of three forms of cost-benefit decision making: effort-, delay-, and risk-based decision making. In this review, we detail the current understanding of the functional circuits that subserve each form of decision making. We highlight the extensive literature by detailing the ability of dopamine to influence decisions by modulating structures within these circuits. Since acetylcholine projects to all of the same important structures, we propose several ways in which the cholinergic system may play a local modulatory role that will allow it to shape these behaviors. A greater understanding of the contribution of the cholinergic system to cost-benefit decisions will permit us to better link the decision and memory processes, and this will help us to better understand and/or treat individuals with deficits in a number of higher cognitive functions including decision making, learning, memory, and language. © 2014 Elsevier Inc. All rights reserved.

  14. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  15. Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

    Science.gov (United States)

    Henrickson, Sarah E; Manne, Sasikanth; Dolfi, Douglas V; Mansfield, Kathleen D; Parkhouse, Kaela; Mistry, Rakesh D; Alpern, Elizabeth R; Hensley, Scott E; Sullivan, Kathleen E; Coffin, Susan E; Wherry, E John

    2018-01-09

    Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

    Science.gov (United States)

    Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2017-09-01

    Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

  17. HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

    Science.gov (United States)

    Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

    2018-05-18

    Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

  18. Thin Film Transistor Control Circuitry for MEMS Acoustic Transducers

    Science.gov (United States)

    Daugherty, Robin

    This work seeks to develop a practical solution for short range ultrasonic communications and produce an integrated array of acoustic transmitters on a flexible substrate. This is done using flexible thin film transistor (TFT) and micro electromechanical systems (MEMS). The goal is to develop a flexible system capable of communicating in the ultrasonic frequency range at a distance of 10-100 meters. This requires a great deal of innovation on the part of the FDC team developing the TFT driving circuitry and the MEMS team adapting the technology for fabrication on a flexible substrate. The technologies required for this research are independently developed. The TFT development is driven primarily by research into flexible displays. The MEMS development is driving by research in biosensors and micro actuators. This project involves the integration of TFT flexible circuit capabilities with MEMS micro actuators in the novel area of flexible acoustic transmitter arrays. This thesis focuses on the design, testing and analysis of the circuit components required for this project.

  19. The Neural Circuitry of Expertise: Perceptual Learning and Social Cognition

    Directory of Open Access Journals (Sweden)

    Michael eHarre

    2013-12-01

    Full Text Available Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is likely a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviourally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations. Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and

  20. Intensity of anxiety is modified via complex integrative stress circuitries.

    Science.gov (United States)

    Smith, Justin P; Prince, Melissa A; Achua, Justin K; Robertson, James M; Anderson, Raymond T; Ronan, Patrick J; Summers, Cliff H

    2016-01-01

    Escalation of anxious behavior while environmentally and socially relevant contextual events amplify the intensity of emotional response produces a testable gradient of anxiety shaped by integrative circuitries. Apprehension of the Stress-Alternatives Model apparatus (SAM) oval open field (OF) is measured by the active latency to escape, and is delayed by unfamiliarity with the passageway. Familiar OF escape is the least anxious behavior along the continuum, which can be reduced by anxiolytics such as icv neuropeptide S (NPS). Social aggression increases anxiousness in the SAM, reducing the number of mice willing to escape by 50%. The apprehension accompanying escape during social aggression is diminished by anxiolytics, such as exercise and corticotropin releasing-factor receptor 1 (CRF1) antagonism, but exacerbated by anxiogenic treatment, like antagonism of α2-adrenoreceptors. What is more, the anxiolytic CRF1 and anxiogenic α2-adrenoreceptor antagonists also modify behavioral phenotypes, with CRF1 antagonism allowing escape by previously submissive animals, and α2-adrenoreceptor antagonism hindering escape in mice that previously engaged in it. Gene expression of NPS and brain-derived neurotrophic factor (BDNF) in the central amygdala (CeA), as well as corticosterone secretion, increased concomitantly with the escalating anxious content of the mouse-specific anxiety continuum. The general trend of CeA NPS and BDNF expression suggested that NPS production was promoted by increasing anxiousness, and that BDNF synthesis was associated with learning about ever-more anxious conditions. The intensity gradient for anxious behavior resulting from varying contextual conditions may yield an improved conceptualization of the complexity of mechanisms producing the natural continuum of human anxious conditions, and potential therapies that arise therefrom. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice

    Science.gov (United States)

    Hunt, Robert F.; Scheff, Stephen W.; Smith, Bret N.

    2011-01-01

    Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus. PMID:21543618

  2. Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.

    Science.gov (United States)

    Gan, Zhenji; Rumsey, John; Hazen, Bethany C; Lai, Ling; Leone, Teresa C; Vega, Rick B; Xie, Hui; Conley, Kevin E; Auwerx, Johan; Smith, Steven R; Olson, Eric N; Kralli, Anastasia; Kelly, Daniel P

    2013-06-01

    The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

  3. Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Russ

    2013-09-01

    Full Text Available During perinatal development, corticospinal tract (CST projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65. In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of descending spinal pathways, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

  4. Neurobiological Programming of Early Life Stress: Functional Development of Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related Psychopathology.

    Science.gov (United States)

    VanTieghem, Michelle R; Tottenham, Nim

    2017-04-25

    Early adverse experiences are associated with heighted vulnerability for stress-related psychopathology across the lifespan. While extensive work has investigated the effects of early adversity on neurobiology in adulthood, developmental approaches can provide further insight on the neurobiological mechanisms that link early experiences and long-term mental health outcomes. In the current review, we discuss the role of emotion regulation circuitry implicated in stress-related psychopathology from a developmental and transdiagnostic perspective. We highlight converging evidence suggesting that multiple forms of early adverse experiences impact the functional development of amygdala-prefrontal circuitry. Next, we discuss how adversity-induced alterations in amygdala-prefrontal development are associated with symptoms of emotion dysregulation and psychopathology. Additionally, we discuss potential mechanisms through which protective factors may buffer the effects of early adversity on amygdala-prefrontal development to confer more adaptive long-term outcomes. Finally, we consider limitations of the existing literature and make suggestions for future longitudinal and translational research that can better elucidate the mechanisms linking early adversity, neurobiology, and emotional phenotypes. Together, these findings may provide further insight into the neuro-developmental mechanisms underlying the emergence of adversity-related emotional disorders and facilitate the development of targeted interventions that can ameliorate risk for psychopathology in youth exposed to early life stress.

  5. United in Diversity : A Physiological and Molecular Characterization of Subpopulations in the Basal Ganglia Circuitry

    OpenAIRE

    Viereckel, Thomas

    2017-01-01

    The Basal Ganglia consist of a number of different nuclei that form a diverse circuitry of GABAergic, dopaminergic and glutamatergic neurons. This complex network is further organized in subcircuits that govern limbic and motor functions in humans and other vertebrates. Due to the interconnection of the individual structures, dysfunction in one area or cell population can affect the entire network, leading to synaptic and molecular alterations in the circuitry as a whole. The studies in this ...

  6. Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells

    Science.gov (United States)

    Mortusewicz, Oliver; Amé, Jean-Christophe; Leonhardt, Heinrich

    2007-01-01

    Genome integrity is constantly threatened by DNA lesions arising from numerous exogenous and endogenous sources. Survival depends on immediate recognition of these lesions and rapid recruitment of repair factors. Using laser microirradiation and live cell microscopy we found that the DNA-damage dependent poly(ADP-ribose) polymerases (PARP) PARP-1 and PARP-2 are recruited to DNA damage sites, however, with different kinetics and roles. With specific PARP inhibitors and mutations, we could show that the initial recruitment of PARP-1 is mediated by the DNA-binding domain. PARP-1 activation and localized poly(ADP-ribose) synthesis then generates binding sites for a second wave of PARP-1 recruitment and for the rapid accumulation of the loading platform XRCC1 at repair sites. Further PARP-1 poly(ADP-ribosyl)ation eventually initiates the release of PARP-1. We conclude that feedback regulated recruitment of PARP-1 and concomitant local poly(ADP-ribosyl)ation at DNA lesions amplifies a signal for rapid recruitment of repair factors enabling efficient restoration of genome integrity. PMID:17982172

  7. Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep.

    Science.gov (United States)

    Potdar, Sheetal; Sheeba, Vasu

    2013-06-01

    Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

  8. Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex-specific manner.

    Science.gov (United States)

    Dickens, M J; Balthazart, J; Cornil, C A

    2012-10-01

    Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, nongenomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce, respectively, a rapid inhibition or increase in preoptic aromatase activity (AA). In the present study, we tested quail that were either nonstressed or acutely stressed (15 min of restraint) immediately before sexual interaction (5 min) with stressed or nonstressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: males did not show any effect of partner status, whereas females responded to both their stress exposure and the male partner's stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner's exhibition of sexually aggressive behaviour, suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple: sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. By contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner's stress exposure, and female-directed male behaviour. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

  9. Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

    Science.gov (United States)

    Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

    2018-05-22

    The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface

  10. Dopaminergic circuitry and risk/reward decision making: implications for schizophrenia.

    Science.gov (United States)

    Stopper, Colin M; Floresco, Stan B

    2015-01-01

    Abnormal reinforcement learning and representations of reward value are present in schizophrenia, and these impairments can manifest as deficits in risk/reward decision making. These abnormalities may be due in part to dopaminergic dysfunction within cortico-limbic-striatal circuitry. Evidence from studies with laboratory animal have revealed that normal DA activity within different nodes of these circuits is critical for mediating dissociable processes that can refine decision biases. Moreover, both phasic and tonic dopamine transmission appear to play separate yet complementary roles in these processes. Tonic dopamine release within the prefrontal cortex and nucleus accumbens, serves as a "running rate-meter" of reward and reflects contextual information such as reward uncertainty and overt choice behavior. On the other hand, manipulations of outcome-related phasic dopamine bursts and dips suggest these signals provide rapid feedback to allow for quick adjustments in choice as reward contingencies change. The lateral habenula is a key input to the DA system that phasic signals is necessary for expressing subjective decision biases; as suppression of activity within this nucleus leads to catastrophic impairments in decision making and random patterns of choice behavior. As schizophrenia is characterized by impairments in using positive and negative feedback to appropriately guide decision making, these findings suggest that these deficits in these processes may be mediated, at least in part, by abnormalities in both tonic and phasic dopamine transmission. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. Rapid top-down regulation of plant C:N:P stoichiometry by grasshoppers in an Inner Mongolia grassland ecosystem.

    Science.gov (United States)

    Zhang, Guangming; Han, Xingguo; Elser, James J

    2011-05-01

    Understanding how food web interactions alter the processing of limiting nutrient elements is an important goal of ecosystem ecology. An experiment manipulating densities of the grasshopper Oedaleus asiaticus was performed to assess top-down effects of grasshoppers on C:N:P stoichiometry of plants and soil in a grassland ecosystem in Inner Mongolia (China). With increased grasshopper feeding, plant biomass declined fourfold, litter abundance increased 30%, and the plant community became dominated by non-host plant taxa. Plant stoichiometric response depended on whether or not the plant was a grasshopper host food species: C:N and C:P ratios increased with increasing grasshopper density (GD) for host plants but decreased in non-host plants. These data suggest either a direct transfer of grasshopper-recycled nutrients from host to non-host plants or a release of non-host plants from nutrient competition with heavily grazed host plants. Litterfall C:N and C:P decreased across moderate levels of grasshopper density but no effects on C:N:P stoichiometry in the surface soil were observed, possibly due to the short experimental period. Our observations of divergent C:N:P stoichiometric response among plant species highlight the important role of grasshopper herbivory in regulating plant community structure and nutrient cycling in grassland ecosystems.

  12. A molecular toolbox for rapid generation of viral vectors to up- or down-regulate in vivo neuronal gene expression

    Directory of Open Access Journals (Sweden)

    Melanie D. White

    2011-07-01

    Full Text Available We introduce a molecular toolbox for manipulation of neuronal gene expression in vivo. The toolbox includes promoters, ion channels, optogenetic tools, fluorescent proteins and intronic artificial microRNAs. The components are easily assembled into adeno-associated virus (AAV or lentivirus vectors using recombination cloning. We demonstrate assembly of toolbox components into lentivirus and AAV vectors and use these vectors for in vivo expression of inwardly rectifying potassium channels (Kir2.1, Kir3.1 and Kir3.2 and an artificial microRNA targeted against the ion channel HCN1 (HCN1 miR. We show that AAV assembled to express HCN1 miR produces efficacious and specific in vivo knockdown of HCN1 channels. Comparison of in vivo viral transduction using HCN1 miR with mice containing a germ line deletion of HCN1 reveals similar physiological phenotypes in cerebellar Purkinje cells. The easy assembly and re-usability of the toolbox components, together with the ability to up- or down-regulate neuronal gene expression in vivo, may be useful for applications in many areas of neuroscience.

  13. Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.

    Science.gov (United States)

    Wright, Brandon J; Jackson, Meyer B

    2014-07-16

    The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information. Theta burst stimulation of the perforant path potentiated responses throughout the molecular layer, but left responses in the CA3 region unchanged. By contrast, theta burst stimulation of the granule cell layer potentiated responses throughout the molecular layer, as well as in the CA3 region. Theta burst stimulation of the granule cell layer potentiated CA3 responses not only to granule cell layer stimulation but also to perforant path stimulation. Potentiation of responses in the CA3 region reflected NMDA receptor-dependent LTP of upstream synapses between granule cells and mossy cells, with no detectable contribution from NMDA receptor-independent LTP of local CA3 mossy fiber synapses. Potentiation of transmission to the CA3 region required LTP in both granule cell→mossy cell and mossy cell→granule cell synapses. This bidirectional plasticity enables hilar circuitry to regulate the flow of information through the dentate gyrus and on to the hippocampus. Copyright © 2014 the authors 0270-6474/14/349743-11$15.00/0.

  14. Bilateral primary motor cortex circuitry is modulated due to theta burst stimulation to left dorsal premotor cortex and bimanual training.

    Science.gov (United States)

    Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

    2015-08-27

    Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury. Copyright © 2015. Published by Elsevier B.V.

  15. DNA-decorated carbon-nanotube-based chemical sensors on complementary metal oxide semiconductor circuitry

    International Nuclear Information System (INIS)

    Chen, Chia-Ling; Yang, Chih-Feng; Dokmeci, Mehmet R; Agarwal, Vinay; Sonkusale, Sameer; Kim, Taehoon; Busnaina, Ahmed; Chen, Michelle

    2010-01-01

    We present integration of single-stranded DNA (ss-DNA)-decorated single-walled carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS) circuitry as nanoscale chemical sensors. SWNTs were assembled onto CMOS circuitry via a low voltage dielectrophoretic (DEP) process. Besides, bare SWNTs are reported to be sensitive to various chemicals, and functionalization of SWNTs with biomolecular complexes further enhances the sensing specificity and sensitivity. After decorating ss-DNA on SWNTs, we have found that the sensing response of the gas sensor was enhanced (up to ∼ 300% and ∼ 250% for methanol vapor and isopropanol alcohol vapor, respectively) compared with bare SWNTs. The SWNTs coupled with ss-DNA and their integration on CMOS circuitry demonstrates a step towards realizing ultra-sensitive electronic nose applications.

  16. Design and implementation of high-precision and low-jitter programmable delay circuitry

    International Nuclear Information System (INIS)

    Gao Yuan; Cui Ke; Zhang Hongfei; Luo Chunli; Yang Dongxu; Liang Hao; Wang Jian

    2011-01-01

    A programmable delay circuit design which has characteristics of high-precision, low-jitter, wide-programmable-range and low power is introduced. The delay circuitry uses the scheme which has two parts: the coarse delay and the fine delay that could be controlled separately. Using different coarse delay chip can reach different maximum programmable range. And the fine delay programmable chip has the minimum step which is down to 10 ps. The whole circuitry jitter will be less than 100 ps. The design has been successfully applied in Quantum Key Distribution experiment. (authors)

  17. Optogenetic deconstruction of sleep-wake circuitry in the brain

    Directory of Open Access Journals (Sweden)

    Antoine Adamantidis

    2010-01-01

    Full Text Available How does the brain regulate the sleep-wake cycle? What are the temporal codes of sleep- and wake-promoting neural circuits? How do these circuits interact with each other across the light/dark cycle? Over the past few decades, many studies from a variety of disciplines have made substantial progress in answering these fundamental questions. For example, neurobiologists have identified multiple, redundant wake-promoting circuits in the brainstem, hypothalamus, and basal forebrain. Sleep-promoting circuits have been found in the preoptic area and hypothalamus. One of the greatest challenges in recent years has been to selectively record and manipulate these sleep-wake centers in vivo with high spatial and temporal resolution. Recent developments in microbial opsin-based neuromodulation tools, collectively referred to as “optogenetics,” have provided a novel method to demonstrate causal links between neural activity and specific behaviors. Here, we propose to use optogenetics as a fundamental tool to probe the necessity, sufficiency, and connectivity of defined neural circuits in the regulation of sleep and wakefulness.

  18. Group Membership Modulates the Neural Circuitry Underlying Third Party Punishment.

    Science.gov (United States)

    Morese, Rosalba; Rabellino, Daniela; Sambataro, Fabio; Perussia, Felice; Valentini, Maria Consuelo; Bara, Bruno G; Bosco, Francesca M

    2016-01-01

    This research aims to explore the neural correlates involved in altruistic punishment, parochial altruism and anti-social punishment, using the Third-Party Punishment (TPP) game. In particular, this study considered these punishment behaviors in in-group vs. out-group game settings, to compare how people behave with members of their own national group and with members of another national group. The results showed that participants act altruistically to protect in-group members. This study indicates that norm violation in in-group (but not in out-group) settings results in increased activity in the medial prefrontal cortex and temporo-parietal junction, brain regions involved in the mentalizing network, as the third-party attempts to understand or justify in-group members' behavior. Finally, exploratory analysis during anti-social punishment behavior showed brain activation recruitment of the ventromedial prefrontal cortex, an area associated with altered regulation of emotions.

  19. Sleep and metabolism: role of hypothalamic neuronal circuitry.

    Science.gov (United States)

    Rolls, Asya; Schaich Borg, Jana; de Lecea, Luis

    2010-10-01

    Sleep and metabolism are intertwined physiologically and behaviorally, but the neural systems underlying their coordination are still poorly understood. The hypothalamus is likely to play a major role in the regulation sleep, metabolism, and their interaction. And increasing evidence suggests that hypocretin cells in the lateral hypothalamus may provide particularly important contributions. Here we review: 1) direct interactions between biological arousal and metabolic systems in the hypothalamus, and 2) indirect interactions between these two systems mediated by stress or reward, emphasizing the role of hypocretins. An increased understanding of the mechanisms underlying these interactions may provide novel approaches for the treatment of patients with sleep disorders and obesity, as well as suggest new therapeutic strategies for symptoms of aging, stress, or addiction. Copyright © 2010. Published by Elsevier Ltd.

  20. Enhanced statistical damage identification using frequency-shift information with tunable piezoelectric transducer circuitry

    International Nuclear Information System (INIS)

    Zhao, J; Tang, J; Wang, K W

    2008-01-01

    The frequency-shift-based damage detection method entertains advantages such as global detection capability and easy implementation, but also suffers from drawbacks that include low detection accuracy and sensitivity and the difficulty in identifying damage using a small number of measurable frequencies. Moreover, the damage detection/identification performance is inevitably affected by the uncertainty/variations in the baseline model. In this research, we investigate an enhanced statistical damage identification method using the tunable piezoelectric transducer circuitry. The tunable piezoelectric transducer circuitry can lead to much enriched information on frequency shift (before and after damage occurrence). The circuitry elements, meanwhile, can be directly and accurately measured and thus can be considered uncertainty-free. A statistical damage identification algorithm is formulated which can identify both the mean and variance of the elemental property change. Our analysis indicates that the integration of the tunable piezoelectric transducer circuitry can significantly enhance the robustness of the frequency-shift-based damage identification approach under uncertainty and noise

  1. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  2. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

    NARCIS (Netherlands)

    Bos, P.A.; Montoya, E.R.; Hermans, E.; Keysers, C.; Honk, J. van

    2015-01-01

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have

  3. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

    NARCIS (Netherlands)

    Bos, Peter A; Montoya, Estrella R; Hermans, Erno J; Keysers, C.; van Honk, Jack

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have

  4. Analysis and simulation of the SLD WIC [Warm Iron Calorimeter] PADS hybrid preamplifier circuitry

    International Nuclear Information System (INIS)

    Fox, J.D.; Horelick, D.

    1990-10-01

    The SLD PADS electronics consist of over 9000 channels of charge-sensitive preamplifiers followed by integrated sample/hold data storage, digitizing, and readout circuitry. This paper uses computer simulation techniques to analyze critical performance parameters of the preamplifier hybrid including its interactions with the detector system. Simulation results are presented and verified with measured performance. 6 refs., 9 figs

  5. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  6. CCR4 agonists CCL22 and CCL17 are elevated in pediatric OMS sera: rapid and selective down-regulation of CCL22 by ACTH or corticosteroids.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A; Ransohoff, Richard M

    2013-05-01

    To study the role of Th2-attracting chemokines in opsoclonus-myoclonus syndrome (OMS), a serious neurological paraneoplastic disorder in need of better immunological understanding and therapy. The CCR4 agonists CCL22 and CCL17 were measured in serum by ELISA in children with OMS (238 and 260, respectively), pediatric controls (115 and 143), and other inflammatory neurological disorders (33 and 24). Both CCL22 (+55 %) and CCL17 (+121 %) were significantly elevated in untreated OMS compared to controls and inter-correlated (p OMS also were higher than in OIND (21 %, 41 %). The concentration of CCL22 in ACTH and steroids groups (not IVIg) was 51 % lower than in controls, but only a smaller effect of ACTH on CCL17 was found. Prospective longitudinal studies revealed a precipitous 81 % drop in CCL22 even by the first week of high-dose ACTH therapy, staying below control mean for at least 12 weeks, and a 34 % reduction after 8 months of combined treatment. Response to ACTH was dose-related (r = -0.50, p OMS. Marked and rapid reduction in CCL22, not CCL17, with either ACTH or steroid therapy suggests differential regulation and cellular sources of CCR4 ligands, and CCL22 as a potential candidate biomarker for ACTH or corticosteroid effect.

  7. Post-translational regulation of Oct4 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Jonathan P Saxe

    Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

  8. A Role for the Lateral Dorsal Tegmentum in Memory and Decision Neural Circuitry

    Science.gov (United States)

    Redila, Van; Kinzel, Chantelle; Jo, Yong Sang; Puryear, Corey B.; Mizumori, Sheri J.Y.

    2017-01-01

    A role for the hippocampus in memory is clear, although the mechanism for its contribution remains a matter of debate. Converging evidence suggests that hippocampus evaluates the extent to which context-defining features of events occur as expected. The consequence of mismatches, or prediction error, signals from hippocampus is discussed in terms of its impact on neural circuitry that evaluates the significance of prediction errors: Ventral tegmental area (VTA) dopamine cells burst fire to rewards or cues that predict rewards (Schultz et al., 1997). Although the lateral dorsal tegmentum (LDTg) importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the behavioral significance of the LDTg control is not known. Therefore, we evaluated LDTg functional activity as rats performed a spatial memory task that generates task-dependent reward codes in VTA (Jo et al., 2013; Puryear et al., 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg, Norton et al., 2011). Reversible inactivation of the LDTg significantly impaired choice accuracy. LDTg neurons coded primarily egocentric information in the form of movement velocity, turning behaviors, and behaviors leading up to expected reward locations. A subset of the velocity-tuned LDTg cells also showed high frequency bursts shortly before or after reward encounters, after which they showed tonic elevated firing during consumption of small, but not large, rewards. Cells that fired before reward encounters showed stronger correlations with velocity as rats moved toward, rather than away from, rewarded sites. LDTg neural activity was more strongly regulated by egocentric behaviors than that observed for PPTg or VTA cells that were recorded by Puryear et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing sensory input, all three regions encoded reward magnitude (although in different ways), reward expectation, and reward encounters. Only VTA encoded reward prediction errors. LDTg

  9. A framework for the first-person internal sensation of visual perception in mammals and a comparable circuitry for olfactory perception in Drosophila.

    Science.gov (United States)

    Vadakkan, Kunjumon I

    2015-01-01

    Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species-the olfactory circuitry of the fruit fly Drosophila melanogaster-provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure

  10. Stitching Codeable Circuits: High School Students' Learning About Circuitry and Coding with Electronic Textiles

    Science.gov (United States)

    Litts, Breanne K.; Kafai, Yasmin B.; Lui, Debora A.; Walker, Justice T.; Widman, Sari A.

    2017-10-01

    Learning about circuitry by connecting a battery, light bulb, and wires is a common activity in many science classrooms. In this paper, we expand students' learning about circuitry with electronic textiles, which use conductive thread instead of wires and sewable LEDs instead of lightbulbs, by integrating programming sensor inputs and light outputs and examining how the two domains interact. We implemented an electronic textiles unit with 23 high school students ages 16-17 years who learned how to craft and code circuits with the LilyPad Arduino, an electronic textile construction kit. Our analyses not only confirm significant increases in students' understanding of functional circuits but also showcase students' ability in designing and remixing program code for controlling circuits. In our discussion, we address opportunities and challenges of introducing codeable circuit design for integrating maker activities that include engineering and computing into classrooms.

  11. Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury

    OpenAIRE

    Minassian, Karen; McKay, W. Barry; Binder, Heinrich; Hofstoetter, Ursula S.

    2016-01-01

    Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidur...

  12. Adaptive Supply Voltage Management for Low Power Logic Circuitry Operating at Subthreshold

    OpenAIRE

    Rehan Ahmed

    2015-01-01

    With the rise in demand of portable hand held devices and with the rise in application of wireless sensor networks and RFID reduction of total power consumption has become a necessity. To save power we operate the logic circuitry of our devices at sub-threshold. In sub-threshold the drain current is exponentially dependent on the threshold voltage hence the threshold variation causes profound variation of ION and IOFF the ratio of which affect the speed of a circuit drastically. S...

  13. Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry

    Directory of Open Access Journals (Sweden)

    Kyoung Joo Cho

    2015-01-01

    Full Text Available Inhibitors of HMG-CoA reductase (statins, widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI. Using the wheat germ agglutinin (WGA transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC, where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

  14. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

    Science.gov (United States)

    Dichter, Gabriel S; Damiano, Cara A; Allen, John A

    2012-07-06

    This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  15. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S

    2012-07-01

    Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  16. Stress, trauma and PTSD: translational insights into the core synaptic circuitry and its modulation.

    Science.gov (United States)

    Bennett, Maxwell R; Hatton, Sean N; Lagopoulos, Jim

    2016-06-01

    Evidence is considered as to whether behavioral criteria for diagnosis of post-traumatic stress disorder (PTSD) are applicable to that of traumatized animals and whether the phenomena of acquisition, extinction and reactivation of fear behavior in animals are also successfully applicable to humans. This evidence suggests an affirmative answer in both cases. Furthermore, the deficits in gray matter found in PTSD, determined with magnetic resonance imaging, are also observed in traumatized animals, lending neuropsychological support to the use of animals to probe what has gone awry in PTSD. Such animal experiments indicate that the core synaptic circuitry mediating behavior following trauma consists of the amygdala, ventral-medial prefrontal cortex and hippocampus, all of which are modulated by the basal ganglia. It is not clear if this is the case in PTSD as the observations using fMRI are equivocal and open to technical objections. Nevertheless, the effects of the basal ganglia in controlling glutamatergic synaptic transmission through dopaminergic and serotonergic synaptic mechanisms in the core synaptic circuitry provides a ready explanation for why modifying these mechanisms delays extinction in animal models and predisposes towards PTSD. In addition, changes of brain-derived neurotrophic factor (BDNF) in the core synaptic circuitry have significant effects on acquisition and extinction in animal experiments with single nucleotide polymorphisms in the BDNF gene predisposing to PTSD.

  17. Tricky Circuitry

    Science.gov (United States)

    Davies, Tony

    2014-01-01

    Teaching children about circuits and the way electricity works is a "tricky business" because it is invisible. Just imagine all eyes are on the teacher as he or she produces for the class what looks like a ping-pong ball and then, with a wave of their hand, the incredible happens! This wonderful white sphere begins to glow red and a…

  18. Neuroanatomical circuitry between kidney and rostral elements of brain: a virally mediated transsynaptic tracing study in mice.

    Science.gov (United States)

    Zhou, Ye-Ting; He, Zhi-Gang; Liu, Tao-Tao; Feng, Mao-Hui; Zhang, Ding-Yu; Xiang, Hong-Bing

    2017-02-01

    The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3-6 days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice. PRV-614 infected neurons were detected in a number of mesencephalic (e.g. central amygdala nucleus), telencephalic regions and motor cortex. These divisions included the preoptic area (POA), dorsomedial hypothalamus (DMH), lateral hypothalamus, arcuate nucleus (Arc), suprachiasmatic nucleus (SCN), periventricular hypothalamus (PeH), and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN). PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH, Arc, SCN, PeH, PVN, the anterodorsal and medial POA. A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic. PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin. These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

  19. NF-κB–YY1–miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma

    Science.gov (United States)

    Wang, Huating; Garzon, Ramiro; Sun, Hao; Ladner, Katherine J.; Singh, Ravi; Dahlman, Jason; Cheng, Alfred; Hall, Brett M.; Qualman, Stephen J.; Chandler, Dawn S.; Croce, Carlo M.; Guttridge, Denis C.

    2008-01-01

    SUMMARY Studies support the importance of microRNAs in physiological and pathological processes. Here we describe the regulation and function of miR-29 in myogenesis and Rhabdomyosarcoma (RMS). Results demonstrate that in myoblasts miR-29 is repressed by NF-κB acting through YY1 and the Polycomb. During myogenesis, NF-κB and YY1 downregulation causes derepression of miR-29, which in turn accelerates differentiation by targeting its repressor YY1. However, in RMS cells and primary tumors that possess impaired differentiation, miR-29 is epigenetically silenced by an activated NF-κB-YY1 pathway. Reconstitution of miR-29 in RMS in mice inhibits tumor growth and stimulates differentiation, suggesting that miR-29 acts as a tumor suppressor through its pro-myogenic function. Together, results identify a NF-κB–YY1–miR-29 regulatory circuit whose disruption may contribute to RMS. SIGNIFICANCE MicroRNAs regulate skeletal myogenesis, but their impact in muscle diseases is not well understood. Here we describe miR-29 as an enhancer of myogenic differentiation and a suppressor of RMS. We find that miR-29 exists in a regulatory circuit involving NF-κB and YY1. In myoblasts NF-B acts through YY1 to epigenetically suppress miR-29, while during differentiation miR-29 is induced to facilitate myogenesis by a negative feedback on YY1. Significantly, RMS tumors lose miR-29 due to an elevation in NF-B and YY1, and readjustment of miR-29 levels in RMS stimulates differentiation. Thus, myogenesis is dependent on NF-κB–YY1–miR-29 circuitry whose dysfunction may contribute to RMS pathogenesis. Such findings offer potential avenues for the diagnosis and treatment of muscle relevant cancers. PMID:18977326

  20. Microwave Technology for Waste Management Applications Including Disposition of Electronic Circuitry

    International Nuclear Information System (INIS)

    Wicks, G.G.; Clark, D.E.; Schulz, R.L.

    1998-01-01

    Advanced microwave technology is being developed nationally and internationally for a variety of waste management and environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of hazardous components into leach resistant forms. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from the undesirable consequences of hazardous materials. One application of special interest is the treatment of discarded electronic circuitry using a new hybrid microwave treatment process and subsequent reclamation of the precious metals within

  1. Microwave technology for waste management applications including disposition of electronic circuitry

    International Nuclear Information System (INIS)

    Wicks, G.G.; Clark, D.E.; Schulz, R.L.; Folz, D.C.

    1995-01-01

    Microwave technology is being developed nationally and internationally for a variety of environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of selected components. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from undesirable consequences of hazardous materials. Applications of microwave energy for environmental remediation will be discussed. Emphasized will be a newly developed microwave process designed to treat discarded electronic circuitry and reclaim the precious metals within for reuse

  2. SpiCAD: Integrated environment for circuitry simulation with SPICE code

    Energy Technology Data Exchange (ETDEWEB)

    D' Amore, D; Padovini, G; Santomauro, M [Politecnico di Milano (Italy). Dip. di Elettronica

    1991-11-01

    SPICE is one of the most commonly used programs for the simulation of the behaviour of electronic circuits. This article describes in detail the key design characteristics and capabilities of a computer environment called SpiCAD which integrates all the different phases of SPICE based circuitry simulation on a personal computer, i.e., the tracing of the electronics scheme, simulation and visualization of the results so as to help define semiconductor device models, determine input signals, construct macro-models and convert design sketches into formats acceptable to graphic systems.

  3. Circuitry for monitoring a high direct current voltage supply for an ionization chamber

    International Nuclear Information System (INIS)

    1981-01-01

    An arrangement to measure the voltage of the supply and a switching means controlled by this is described. The voltage measurer consists of first and second signal coupling means, the input of the second (connected to the voltage supply) is connected in series with the output of the first. An ionization chamber with this circuitry may be used to monitor the radiation output of a particle accelerator more accurately. Faulty measurements of the dose output, caused by voltages in the earth circuit, are avoided. (U.K.)

  4. Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography

    Directory of Open Access Journals (Sweden)

    Maria A. Bobes

    2016-01-01

    Full Text Available Although Capgras delusion (CD patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF and the inferior longitudinal (ILF. The superior longitudinal fasciculus (SLF and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

  5. Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

    Science.gov (United States)

    Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

    2016-04-01

    Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

  6. Circuitry and plasticity of the dorsal horn--toward a better understanding of neuropathic pain.

    Science.gov (United States)

    West, S J; Bannister, K; Dickenson, A H; Bennett, D L

    2015-08-06

    Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal DH and the radical changes evoked in such circuitry by nerve injury. These changes can be viewed at multiple levels including: synaptic remodeling including enhanced excitatory and reduced inhibitory drive, morphological and electrophysiological changes which are observed both to primary afferent inputs as well as DH neurons, and ultimately circuit-level rewiring which leads to altered connectivity and aberrant processing of sensory inputs in the DH. The DH should not be seen in isolation but is subject to important descending modulation from the brainstem, which is further dysregulated by nerve injury. Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Glucocorticoid acts on a putative G protein-coupled receptor to rapidly regulate the activity of NMDA receptors in hippocampal neurons.

    Science.gov (United States)

    Zhang, Yanmin; Sheng, Hui; Qi, Jinshun; Ma, Bei; Sun, Jihu; Li, Shaofeng; Ni, Xin

    2012-04-01

    Glucocorticoids (GCs) have been demonstrated to act through both genomic and nongenomic mechanisms. The present study demonstrated that corticosterone rapidly suppressed the activity of N-methyl-D-aspartate (NMDA) receptors in cultured hippocampal neurons. The effect was maintained with corticosterone conjugated to bovine serum albumin and blocked by inhibition of G protein activity with intracellular GDP-β-S application. Corticosterone increased GTP-bound G(s) protein and cyclic AMP (cAMP) production, activated phospholipase Cβ(3) (PLC-β(3)), and induced inositol-1,4,5-triphosphate (IP(3)) production. Blocking PLC and the downstream cascades with PLC inhibitor, IP(3) receptor antagonist, Ca(2+) chelator, and protein kinase C (PKC) inhibitors prevented the actions of corticosterone. Blocking adenylate cyclase (AC) and protein kinase A (PKA) caused a decrease in NMDA-evoked currents. Application of corticosterone partly reversed the inhibition of NMDA currents caused by blockage of AC and PKA. Intracerebroventricular administration of corticosterone significantly suppressed long-term potentiation (LTP) in the CA1 region of the hippocampus within 30 min in vivo, implicating the possibly physiological significance of rapid effects of GC on NMDA receptors. Taken together, our results indicate that GCs act on a putative G protein-coupled receptor to activate multiple signaling pathways in hippocampal neurons, and the rapid suppression of NMDA activity by GCs is dependent on PLC and downstream signaling.

  8. Electro-active sensor, method for constructing the same; apparatus and circuitry for detection of electro-active species

    Science.gov (United States)

    Buehler, Martin (Inventor)

    2009-01-01

    An electro-active sensor includes a nonconductive platform with a first electrode set attached with a first side of a nonconductive platform. The first electrode set serves as an electrochemical cell that may be utilized to detect electro-active species in solution. A plurality of electrode sets and a variety of additional electrochemical cells and sensors may be attached with the nonconductive platform. The present invention also includes a method for constructing the aforementioned electro-active sensor. Additionally, an apparatus for detection and observation is disclosed, where the apparatus includes a sealable chamber for insertion of a portion of an electro-active sensor. The apparatus allows for monitoring and detection activities. Allowing for control of attached cells and sensors, a dual-mode circuitry is also disclosed. The dual-mode circuitry includes a switch, allowing the circuitry to be switched from a potentiostat to a galvanostat mode.

  9. Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

    Science.gov (United States)

    Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

    2014-01-01

    Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

  10. Understanding overbidding: using the neural circuitry of reward to design economic auctions.

    Science.gov (United States)

    Delgado, Mauricio R; Schotter, Andrew; Ozbay, Erkut Y; Phelps, Elizabeth A

    2008-09-26

    We take advantage of our knowledge of the neural circuitry of reward to investigate a puzzling economic phenomenon: Why do people overbid in auctions? Using functional magnetic resonance imaging (fMRI), we observed that the social competition inherent in an auction results in a more pronounced blood oxygen level-dependent (BOLD) response to loss in the striatum, with greater overbidding correlated with the magnitude of this response. Leveraging these neuroimaging results, we design a behavioral experiment that demonstrates that framing an experimental auction to emphasize loss increases overbidding. These results highlight a role for the contemplation of loss in understanding the tendency to bid "too high." Current economic theories suggest overbidding may result from either "joy of winning" or risk aversion. By combining neuroeconomic and behavioral economic techniques, we find that another factor, namely loss contemplation in a social context, may mediate overbidding in auctions.

  11. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

    Science.gov (United States)

    Li, Jiang; Green, Alexander A.; Yan, Hao; Fan, Chunhai

    2017-11-01

    Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

  12. The role of BDNF in depression on the basis of its location in the neural circuitry

    Institute of Scientific and Technical Information of China (English)

    Hui YU; Zhe-yu CHEN

    2011-01-01

    Depression is one of the most prevalent and life-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Most attention in the field has focused on hippocampal and frontal cortical regions for their roles in depression and antidepressant action. While these regions no doubt play important roles in the mental illness, there is compelling evi-dence that other brain regions are also involved. Brain-derived neurotrophic factor (BDNF) is broadly expressed in the developing and adult mammalian brain and has been implicated in development, neural regeneration, synaptic transmission, synaptic plasticity and neurogenesis. Recently BDNF has been shown to play an important role in the pathophysiology of depression, however there are con-troversial reports about the effects of BDNF on depression. Here, we present an overview of the current knowledge concerning BDNF actions and associated intracellular signaling in hippocampus, prefrontal cortex, nucleus accumbens (NAc) and amygdala as their rela-tion to depression.

  13. 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.

  14. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr., Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bobrek, Miljko [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-12-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios where human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments due the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is the final report of the activities involving the NEET 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays. We present a detailed functional block diagram of the proposed data acquisition system, the thought process leading to technical decisions, the implemented system, and the tested results from the systems. This system will be capable of monitoring at least three parameters of importance to nuclear reactor monitoring: temperature, radiation level, and pressure.

  15. "Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

    Science.gov (United States)

    Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

    2012-01-01

    In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions.

  16. Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

    Science.gov (United States)

    Schreiter, S; Spengler, S; Willert, A; Mohnke, S; Herold, D; Erk, S; Romanczuk-Seiferth, N; Quinlivan, E; Hindi-Attar, C; Banzhaf, C; Wackerhagen, C; Romund, L; Garbusow, M; Stamm, T; Heinz, A; Walter, H; Bermpohl, F

    2016-11-01

    Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

  17. Neuroanatomical circuitry associated with exploratory eye movement in schizophrenia: a voxel-based morphometric study.

    Directory of Open Access Journals (Sweden)

    Linlin Qiu

    Full Text Available Schizophrenic patients present abnormalities in a variety of eye movement tasks. Exploratory eye movement (EEM dysfunction appears to be particularly specific to schizophrenia. However, the underlying mechanisms of EEM dysfunction in schizophrenia are not clearly understood. To assess the potential neuroanatomical substrates of EEM, we recorded EEM performance and conducted a voxel-based morphometric analysis of gray matter in 33 schizophrenic patients and 29 well matched healthy controls. In schizophrenic patients, decreased responsive search score (RSS and widespread gray matter density (GMD reductions were observed. Moreover, the RSS was positively correlated with GMD in distributed brain regions in schizophrenic patients. Furthermore, in schizophrenic patients, some brain regions with neuroanatomical deficits overlapped with some ones associated with RSS. These brain regions constituted an occipito-tempro-frontal circuitry involved in visual information processing and eye movement control, including the left calcarine cortex [Brodmann area (BA 17], the left cuneus (BA 18, the left superior occipital cortex (BA 18/19, the left superior frontal gyrus (BA 6, the left cerebellum, the right lingual cortex (BA 17/18, the right middle occipital cortex (BA19, the right inferior temporal cortex (BA 37, the right dorsolateral prefrontal cortex (BA 46 and bilateral precentral gyri (BA 6 extending to the frontal eye fields (FEF, BA 8. To our knowledge, we firstly reported empirical evidence that gray matter loss in the occipito-tempro-frontal neuroanatomical circuitry of visual processing system was associated with EEM performance in schizophrenia, which may be helpful for the future effort to reveal the underlying neural mechanisms for EEM disturbances in schizophrenia.

  18. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

    Directory of Open Access Journals (Sweden)

    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  19. Anesthetics rapidly promote synaptogenesis during a critical period of brain development.

    Directory of Open Access Journals (Sweden)

    Mathias De Roo

    Full Text Available Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.

  20. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  1. Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS).

    Science.gov (United States)

    George, Mark S; Nahas, Ziad; Li, Xiangbao; Kozel, F Andrew; Anderson, Berry; Yamanaka, Kaori; Chae, Jeong-Ho; Foust, Milton J

    2002-10-01

    Advances in understanding the functional and structural anatomy of depression outlined in this issue set the stage for attempting to manipulate implicated brain regions as potential antidepressant therapies. On the one hand, these circuit- and device-based approaches to treating depression are not new. Electroconvulsive therapy (ECT) dates back to the beginning of modern biologic psychiatry with the discovery and rapid increase of first chemical (around 1910), and then later ECT. On the other hand, this area represents an important paradigm shift with treatments that are radical and different. A dizzying array of diverse technologies now allows researchers to stimulate the brain in undreamed of ways. However, the approaches described in this article are still considered experimental and are not approved for use in the United States by the Food and Drug Administration (FDA), except ECT, which predates the FDA. These device-based approaches to brain stimulation offer promise as potential acute and even longterm treatments. Additionally, the research determining whether and how these devices work to influence mood promises to help unravel the neurophysiology of mood regulation. These novel treatments are thus the translational tools to bridge from advances in brain imaging, into new treatments for depressed patients. Copyright 2002, Elsevier Science (USA). All rights reserved.

  2. CHARACTERIZATION OF OZONE EMISSIONS FROM AIR CLEANERS EQUIPPED WITH OZONE GENERATORS AND SENSOR AND FEEDBACK CONTROL CIRCUITRY

    Science.gov (United States)

    The paper give results of a characterization of ozone emissions from air cleaners equipped with ozone generators and sensor and feedback control circuitry. Ozone emission rates of several consumer appliances, marketed as indoor air treatment or air purification systems, were det...

  3. Genome-wide DNA methylation alterations of Alternanthera philoxeroides in natural and manipulated habitats: implications for epigenetic regulation of rapid responses to environmental fluctuation and phenotypic variation.

    Science.gov (United States)

    Gao, Lexuan; Geng, Yupeng; Li, Bo; Chen, Jiakuan; Yang, Ji

    2010-11-01

    Alternanthera philoxeroides (alligator weed) is an invasive weed that can colonize both aquatic and terrestrial habitats. Individuals growing in different habitats exhibit extensive phenotypic variation but little genetic differentiation in its introduced range. The mechanisms underpinning the wide range of phenotypic variation and rapid adaptation to novel and changing environments remain uncharacterized. In this study, we examined the epigenetic variation and its correlation with phenotypic variation in plants exposed to natural and manipulated environmental variability. Genome-wide methylation profiling using methylation-sensitive amplified fragment length polymorphism (MSAP) revealed considerable DNA methylation polymorphisms within and between natural populations. Plants of different source populations not only underwent significant morphological changes in common garden environments, but also underwent a genome-wide epigenetic reprogramming in response to different treatments. Methylation alterations associated with response to different water availability were detected in 78.2% (169/216) of common garden induced polymorphic sites, demonstrating the environmental sensitivity and flexibility of the epigenetic regulatory system. These data provide evidence of the correlation between epigenetic reprogramming and the reversible phenotypic response of alligator weed to particular environmental factors. © 2010 Blackwell Publishing Ltd.

  4. On Certain New Methodology for Reducing Sensor and Readout Electronics Circuitry Noise in Digital Domain

    Science.gov (United States)

    Kizhner, Semion; Miko, Joseph; Bradley, Damon; Heinzen, Katherine

    2008-01-01

    NASA Hubble Space Telescope (HST) and upcoming cosmology science missions carry instruments with multiple focal planes populated with many large sensor detector arrays. These sensors are passively cooled to low temperatures for low-level light (L3) and near-infrared (NIR) signal detection, and the sensor readout electronics circuitry must perform at extremely low noise levels to enable new required science measurements. Because we are at the technological edge of enhanced performance for sensors and readout electronics circuitry, as determined by thermal noise level at given temperature in analog domain, we must find new ways of further compensating for the noise in the signal digital domain. To facilitate this new approach, state-of-the-art sensors are augmented at their array hardware boundaries by non-illuminated reference pixels, which can be used to reduce noise attributed to sensors. There are a few proposed methodologies of processing in the digital domain the information carried by reference pixels, as employed by the Hubble Space Telescope and the James Webb Space Telescope Projects. These methods involve using spatial and temporal statistical parameters derived from boundary reference pixel information to enhance the active (non-reference) pixel signals. To make a step beyond this heritage methodology, we apply the NASA-developed technology known as the Hilbert- Huang Transform Data Processing System (HHT-DPS) for reference pixel information processing and its utilization in reconfigurable hardware on-board a spaceflight instrument or post-processing on the ground. The methodology examines signal processing for a 2-D domain, in which high-variance components of the thermal noise are carried by both active and reference pixels, similar to that in processing of low-voltage differential signals and subtraction of a single analog reference pixel from all active pixels on the sensor. Heritage methods using the aforementioned statistical parameters in the

  5. Responses of Rapid Viscoanalyzer Profile and Other Rice Grain Qualities to Exogenously Applied Plant Growth Regulators under High Day and High Night Temperatures.

    Directory of Open Access Journals (Sweden)

    Shah Fahad

    Full Text Available High-temperature stress degrades the grain quality of rice; nevertheless, the exogenous application of plant growth regulators (PGRs might alleviate the negative effects of high temperatures. In the present study, we investigated the responses of rice grain quality to exogenously applied PGRs under high day temperatures (HDT and high night temperatures (HNT under controlled conditions. Four different combinations of ascorbic acid (Vc, alpha-tocopherol (Ve, brassinosteroids (Br, methyl jasmonates (MeJA and triazoles (Tr were exogenously applied to two rice cultivars (IR-64 and Huanghuazhan prior to the high-temperature treatment. A Nothing applied Control (NAC was included for comparison. The results demonstrated that high-temperature stress was detrimental for grain appearance and milling qualities and that both HDT and HNT reduced the grain length, grain width, grain area, head rice percentage and milled rice percentage but increased the chalkiness percentage and percent area of endosperm chalkiness in both cultivars compared with ambient temperature (AT. Significantly higher grain breakdown, set back, consistence viscosity and gelatinization temperature, and significantly lower peak, trough and final viscosities were observed under high-temperature stress compared with AT. Thus, HNT was more devastating for grain quality than HDT. The exogenous application of PGRs ameliorated the adverse effects of high temperature in both rice cultivars, and Vc+Ve+MejA+Br was the best combination for both cultivars under high temperature stress.

  6. Rapid regulation of the plasma membrane H⁺-ATPase activity is essential to salinity tolerance in two halophyte species, Atriplex lentiformis and Chenopodium quinoa.

    Science.gov (United States)

    Bose, Jayakumar; Rodrigo-Moreno, Ana; Lai, Diwen; Xie, Yanjie; Shen, Wenbiao; Shabala, Sergey

    2015-02-01

    The activity of H(+)-ATPase is essential for energizing the plasma membrane. It provides the driving force for potassium retention and uptake through voltage-gated channels and for Na(+) exclusion via Na(+)/H(+) exchangers. Both of these traits are central to plant salinity tolerance; however, whether the increased activity of H(+)-ATPase is a constitutive trait in halophyte species and whether this activity is upregulated at either the transcriptional or post-translation level remain disputed. The kinetics of salt-induced net H(+), Na(+) and K(+) fluxes, membrane potential and AHA1/2/3 expression changes in the roots of two halophyte species, Atriplex lentiformis (saltbush) and Chenopodium quinoa (quinoa), were compared with data obtained from Arabidopsis thaliana roots. Intrinsic (steady-state) membrane potential values were more negative in A. lentiformis and C. quinoa compared with arabidopsis (-144 ± 3·3, -138 ± 5·4 and -128 ± 3·3 mV, respectively). Treatment with 100 mm NaCl depolarized the root plasma membrane, an effect that was much stronger in arabidopsis. The extent of plasma membrane depolarization positively correlated with NaCl-induced stimulation of vanadate-sensitive H(+) efflux, Na(+) efflux and K(+) retention in roots (quinoa > saltbush > arabidopsis). NaCl-induced stimulation of H(+) efflux was most pronounced in the root elongation zone. In contrast, H(+)-ATPase AHA transcript levels were much higher in arabidopsis compared with quinoa plants, and 100 mm NaCl treatment led to a further 3-fold increase in AHA1 and AHA2 transcripts in arabidopsis but not in quinoa. Enhanced salinity tolerance in the halophyte species studied here is not related to the constitutively higher AHA transcript levels in the root epidermis, but to the plant's ability to rapidly upregulate plasma membrane H(+)-ATPase upon salinity treatment. This is necessary for assisting plants to maintain highly negative membrane potential values and to

  7. Rapid regulation of the plasma membrane H+-ATPase activity is essential to salinity tolerance in two halophyte species, Atriplex lentiformis and Chenopodium quinoa

    Science.gov (United States)

    Bose, Jayakumar; Rodrigo-Moreno, Ana; Lai, Diwen; Xie, Yanjie; Shen, Wenbiao; Shabala, Sergey

    2015-01-01

    Background and Aims The activity of H+-ATPase is essential for energizing the plasma membrane. It provides the driving force for potassium retention and uptake through voltage-gated channels and for Na+ exclusion via Na+/H+ exchangers. Both of these traits are central to plant salinity tolerance; however, whether the increased activity of H+-ATPase is a constitutive trait in halophyte species and whether this activity is upregulated at either the transcriptional or post-translation level remain disputed. Methods The kinetics of salt-induced net H+, Na+ and K+ fluxes, membrane potential and AHA1/2/3 expression changes in the roots of two halophyte species, Atriplex lentiformis (saltbush) and Chenopodium quinoa (quinoa), were compared with data obtained from Arabidopsis thaliana roots. Key Results Intrinsic (steady-state) membrane potential values were more negative in A. lentiformis and C. quinoa compared with arabidopsis (−144 ± 3·3, −138 ± 5·4 and −128 ± 3·3 mV, respectively). Treatment with 100 mm NaCl depolarized the root plasma membrane, an effect that was much stronger in arabidopsis. The extent of plasma membrane depolarization positively correlated with NaCl-induced stimulation of vanadate-sensitive H+ efflux, Na+ efflux and K+ retention in roots (quinoa > saltbush > arabidopsis). NaCl-induced stimulation of H+ efflux was most pronounced in the root elongation zone. In contrast, H+-ATPase AHA transcript levels were much higher in arabidopsis compared with quinoa plants, and 100 mm NaCl treatment led to a further 3-fold increase in AHA1 and AHA2 transcripts in arabidopsis but not in quinoa. Conclusions Enhanced salinity tolerance in the halophyte species studied here is not related to the constitutively higher AHA transcript levels in the root epidermis, but to the plant’s ability to rapidly upregulate plasma membrane H+-ATPase upon salinity treatment. This is necessary for assisting plants to maintain highly negative

  8. Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

    Science.gov (United States)

    Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne

    2015-06-30

    Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

    Science.gov (United States)

    Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

    2013-01-01

    Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

  10. The neural circuitry of visual artistic production and appreciation: A proposition

    Directory of Open Access Journals (Sweden)

    Ambar Chakravarty

    2012-01-01

    Full Text Available The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF, relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

  11. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design

    Energy Technology Data Exchange (ETDEWEB)

    Kia, Kaveh Kazemi [Department of Electrical and Computer Engineering, Islamic Azad University of Bonab, Bonab (Iran, Islamic Republic of); Bonabi, Fahimeh [Department of Engineering, Islamic Azad University of Bonab, Bonab (Iran, Islamic Republic of)

    2012-12-15

    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 {mu}s. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  12. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: circuitry and mechanical design.

    Science.gov (United States)

    Kia, Kaveh Kazemi; Bonabi, Fahimeh

    2012-12-01

    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 μs. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  13. Assessing Ink Transfer Performance of Gravure-Offset Fine-Line Circuitry Printing

    Science.gov (United States)

    Cheng, Hsien-Chie; Chen, You-Wei; Chen, Wen-Hwa; Lu, Su-Tsai; Lin, Shih-Ming

    2018-03-01

    In this study, the printing mechanism and performance of gravure-offset fine-line circuitry printing technology are investigated in terms of key printing parameters through experimental and theoretical analyses. First, the contact angles of the ink deposited on different substrates, blankets, and gravure metal plates are experimentally determined; moreover, their temperature and solvent content dependences are analyzed. Next, the ink solvent absorption and evaporation behaviors of the blankets at different temperatures, times, and numbers of printing repetitions are characterized by conducting experiments. In addition, while printing repeatedly, the surface characteristics of the blankets, such as the contact angle, vary with the amount of absorbed ink solvent, further affecting the ink transfer performance (ratio) and printing quality. Accordingly, the surface effect of the blanket due to ink solvent absorption on the ink contact angle is analyzed. Furthermore, the amount of ink transferred from the gravure plate to the blanket in the "off process" and from the blanket to the substrate in the "set process" is evaluated by conducting a simplified plate-to-plate experiment. The influences of loading rate (printing velocity), temperature, and solvent content on the ink transfer performance are addressed. Finally, the ink transfer mechanism is theoretically analyzed for different solvent contents using Surface Evolver. The calculation results are compared with those of the experiment.

  14. Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

    Science.gov (United States)

    Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2013-01-01

    There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

  15. Dynamic neural network models of the premotoneuronal circuitry controlling wrist movements in primates.

    Science.gov (United States)

    Maier, M A; Shupe, L E; Fetz, E E

    2005-10-01

    Dynamic recurrent neural networks were derived to simulate neuronal populations generating bidirectional wrist movements in the monkey. The models incorporate anatomical connections of cortical and rubral neurons, muscle afferents, segmental interneurons and motoneurons; they also incorporate the response profiles of four populations of neurons observed in behaving monkeys. The networks were derived by gradient descent algorithms to generate the eight characteristic patterns of motor unit activations observed during alternating flexion-extension wrist movements. The resulting model generated the appropriate input-output transforms and developed connection strengths resembling those in physiological pathways. We found that this network could be further trained to simulate additional tasks, such as experimentally observed reflex responses to limb perturbations that stretched or shortened the active muscles, and scaling of response amplitudes in proportion to inputs. In the final comprehensive network, motor units are driven by the combined activity of cortical, rubral, spinal and afferent units during step tracking and perturbations. The model displayed many emergent properties corresponding to physiological characteristics. The resulting neural network provides a working model of premotoneuronal circuitry and elucidates the neural mechanisms controlling motoneuron activity. It also predicts several features to be experimentally tested, for example the consequences of eliminating inhibitory connections in cortex and red nucleus. It also reveals that co-contraction can be achieved by simultaneous activation of the flexor and extensor circuits without invoking features specific to co-contraction.

  16. The neural circuitry of visual artistic production and appreciation: A proposition.

    Science.gov (United States)

    Chakravarty, Ambar

    2012-04-01

    The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

  17. First realization of a tracking detector for high energy physics experiments based on Josephson digital readout circuitry

    CERN Document Server

    Pagano, S; Esposito, A P; Mukhanov, O; Rylov, S

    1999-01-01

    We have designed and realized a prototype of a high energy particle microstrip detector with Josephson readout circuits. The key features of this device are: minimum ionizing particle sensitivity, due to the use of semiconductive sensors, fast speed and radiation hardness, due to the use of superconductive circuitry, and current discrimination, which allows the use of several types of semiconductors as detector (Si, GaAs, CVD-diamond) without loss in performances. The Josephson circuitry, made by a combination of RSFQ and latching logic gates, realizes an 8-bit current discriminator and parallel to serial converter and can be directly interfaced to room temperature electronics. This device, which is designed for application as vertex detector for the Compass and LHC-B accelerator experiments, has been tested with small radioactive sources acid will undergo to a test beam at the CERN SPS facility with 24 GeV/c protons. Current results and future perspectives will be reported. (11 refs).

  18. Regulation of body fat mass by the gut microbiota

    DEFF Research Database (Denmark)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik

    2016-01-01

    New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries...

  19. Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.

    Science.gov (United States)

    Icenhour, A; Langhorst, J; Benson, S; Schlamann, M; Hampel, S; Engler, H; Forsting, M; Elsenbruch, S

    2015-01-01

    Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm. During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses. Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement. Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS. © 2014 John Wiley & Sons Ltd.

  20. Effects of direct social experience on trust decisions and neural reward circuitry

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri

    2012-10-01

    Full Text Available The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball tossing game with three fictional partners manipulated to be perceived as good, bad or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction-error (PE learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning

  1. Hyperleptinemia in Neonatally Overfed Female Rats Does Not Dysregulate Feeding Circuitry

    Directory of Open Access Journals (Sweden)

    Ilvana Ziko

    2017-10-01

    Full Text Available Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associated with a short-term disruption in the connectivity of neuropeptide Y (NPY, agouti-related peptide (AgRP, and pro-opiomelanocortin (POMC neurons within the regions of the hypothalamus responsible for control of energy balance and food intake. Female rats that are overfed during the first weeks of their life experience similar changes in circulating leptin levels as well as in their body weight. However, it has not yet been studied whether these metabolic changes are associated with the same central effects as observed in males. Here, we hypothesized that hyperleptinemia associated with neonatal overfeeding would lead to changes in central feeding circuitry in females as it does in males. We assessed hypothalamic NPY, AgRP, and POMC gene expression and immunoreactivity at 7, 12, or 14 days of age, as well as neuronal activation in response to exogenous leptin in neonatally overfed and control female rats. Neonatally overfed female rats were hyperleptinemic and were heavier than controls. However, these metabolic changes were not mirrored centrally by changes in hypothalamic NPY, AGRP, and POMC fiber density. These findings are suggestive of sex differences in the effects of neonatal overfeeding and of differences in the ability of the female and male central systems to respond to changes in the early life nutritional environment.

  2. Effects of Direct Social Experience on Trust Decisions and Neural Reward Circuitry

    Science.gov (United States)

    Fareri, Dominic S.; Chang, Luke J.; Delgado, Mauricio R.

    2012-01-01

    The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball-tossing game with three fictional partners manipulated to be perceived as good, bad, or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball-tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction error learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning mechanisms. PMID:23087604

  3. Hybrid nanowire ion-to-electron transducers for integrated bioelectronic circuitry (Conference Presentation)

    Science.gov (United States)

    Carrad, Damon J.; Mostert, Bernard; Meredith, Paul; Micolich, Adam P.

    2016-09-01

    A key task in bioelectronics is the transduction between ionic/protonic signals and electronic signals at high fidelity. This is a considerable challenge since the two carrier types exhibit intrinsically different physics. We present our work on a new class of organic-inorganic transducing interface utilising semiconducting InAs and GaAs nanowires directly gated with a proton transporting hygroscopic polymer consisting of undoped polyethylene oxide (PEO) patterned to nanoscale dimensions by a newly developed electron-beam lithography process [1]. Remarkably, we find our undoped PEO polymer electrolyte gate dielectric [2] gives equivalent electrical performance to the more traditionally used LiClO4-doped PEO [3], with an ionic conductivity three orders of magnitude higher than previously reported for undoped PEO [4]. The observed behaviour is consistent with proton conduction in PEO. We attribute our undoped PEO-based devices' performance to the small external surface and high surface-to-volume ratio of both the nanowire conducting channel and patterned PEO dielectric in our devices, as well as the enhanced hydration afforded by device processing and atmospheric conditions. In addition to studying the basic transducing mechanisms, we also demonstrate high-fidelity ionic to electronic conversion of a.c. signals at frequencies up to 50 Hz. Moreover, by combining complementary n- and p-type transducers we demonstrate functional hybrid ionic-electronic circuits can achieve logic (NOT operation), and with some further engineering of the nanowire contacts, potentially also amplification. Our device structures have significant potential to be scaled towards realising integrated bioelectronic circuitry. [1] D.J. Carrad et al., Nano Letters 14, 94 (2014). [2] D.J. Carrad et al., Manuscript in preparation (2016). [3] S.H. Kim et al., Advanced Materials 25, 1822 (2013). [4] S.K. Fullerton-Shirey et al., Macromolecules 42, 2142 (2009).

  4. The banana code – Natural blend processing in the olfactory circuitry of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Marco eSchubert

    2014-02-01

    Full Text Available Odor information is predominantly perceived as complex odor blends. For Drosophila melanogaster one of the most attractive blends is emitted by an over-ripe banana. To analyze how the fly’s olfactory system processes natural blends we combined the experimental advantages of gas chromatography and functional imaging (GC-I. In this way, natural banana compounds were presented successively to the fly antenna in close to natural occurring concentrations. This technique allowed us to identify the active odor components, use these compounds as stimuli and measure odor-induced Ca2+ signals in input and output neurons of the Drosophila antennal lobe (AL, the first olfactory neuropil. We demonstrate that mixture interactions of a natural blend are very rare and occur only at the AL output level resulting in a surprisingly linear blend representation. However, the information regarding single components is strongly modulated by the olfactory circuitry within the AL leading to a higher similarity between the representation of individual components and the banana blend. This observed modulation might tune the olfactory system in a way to distinctively categorize odor components and improve the detection of suitable food sources. Functional GC-I thus enables analysis of virtually any unknown natural odorant blend and its components in their relative occurring concentrations and allows characterization of neuronal responses of complete neural assemblies. This technique can be seen as a valuable complementary method to classical GC/electrophysiology techniques, and will be a highly useful tool in future investigations of insect-insect and insect-plant chemical interactions.

  5. Flexible thin film circuitry enabling ubiquitous electronics via post-fabrication customization (Presentation Recording)

    Science.gov (United States)

    Cobb, Brian

    2015-09-01

    For decades, the electronics industry has been accurately described by Moore's Law, where the march towards increasing density and smaller feature sizes has enabled continuous cost reductions and performance improvements. With flexible electronics, this perpetual scaling is not foreseen to occur. Instead, the industry will be dominated by Wright's Law, first proposed in 1936, where increasing demand for high volumes of product will drive costs down. We have demonstrated thin film based circuitry compatible with flexible substrates with high levels of functionality designed for such a high volume industry. This includes a generic 8-bit microprocessor totaling more than 3.5k TFTs operating at 2.1 kHz. We have also developed a post fabrication programming technique via inkjet printing of conductive spots to form a one-time programmable instruction generator, allowing customization of the processor for a specific task. The combination demonstrates the possibility to achieve the high volume production of identical products necessary to reap the benefits promised by Wright's Law, while still retaining the individualization necessary for application differentiation. This is of particular importance in the area of item level identification via RFID, where low cost and individualized identification are necessary. Remotely powered RFID tags have been fabricated using an oxide semiconductor based TFT process. This process is compatible with the post-fabrication printing process to detail individual identification codes, with the goal of producing low cost, high volume flexible tags. The goal is to produce tags compatible with existing NFC communication protocols in order to communicate with readers that are already ubiquitous in the market.

  6. Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.

    Directory of Open Access Journals (Sweden)

    Gaia Olivo

    Full Text Available Few studies have used diffusion tensor imaging (DTI to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED, and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA and mean, radial and axial diffusivities (MD, RD and AD, respectively. Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.

  7. The role of leptin in the regulation of energy balance and adiposity

    NARCIS (Netherlands)

    van Dijk, G

    2001-01-01

    Since its discovery, leptin (a 167-amino acid product of the OB gene) has quickly moved to the forefront as an important hormone for regulation of energy balance. It closes a feedback loop from adipose tissue to hypothalamic neuropeptide-containing neural circuitry involved in regulation of food

  8. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Report 3

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr, Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shelton, Jacob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-03-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios when human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments because of the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is a report of the activities involving Task 3 of the Nuclear Energy Enabling Technologies (NEET) 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays [1]. Evaluation of the performance of the system for both pre- and post-irradiation as well as operation at elevated temperature will be performed. Detailed performance of the system will be documented to ensure the design meets requirements prior to any extended evaluation. A suite of tests will be developed which will allow evaluation before and after irradiation and during temperature. Selection of the radiation exposure facilities will be determined in the early phase of the project. Radiation exposure will consist of total integrated dose (TID) up to 200 kRad or above with several intermediate doses during test. Dose rates will be in various ranges determined by the facility that will be used with a target of 30 kRad/hr. Many samples of the pre-commercial devices to be used will have been tested in previous projects to doses of at least 300 kRad and temperatures up to 125C. The complete systems will therefore be tested for performance at intermediate doses. Extended temperature testing will be performed up to the limit of the commercial sensors. The test suite performed at each test point will consist of operational testing of the three basic

  9. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Mackey, Tim K

    2016-02-03

    The adoption and use of digital forms of direct-to-consumer advertising (also known as "eDTCA") is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA) notices of violations (NOVs) and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the "disruptive" qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored. © 2016 by Kerman University of Medical Sciences.

  10. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Tim K. Mackey

    2016-04-01

    Full Text Available The adoption and use of digital forms of direct-to-consumer advertising (also known as “eDTCA” is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA notices of violations (NOVs and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the “disruptive” qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored.

  11. Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

    Science.gov (United States)

    Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A

    2015-03-01

    Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Goto

    Full Text Available Although left-right (L-R asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

  13. The Neural Basis of and a Common Neural Circuitry in Different Types of Pro-social Behavior

    Directory of Open Access Journals (Sweden)

    Jun Luo

    2018-06-01

    Full Text Available Pro-social behaviors are voluntary behaviors that benefit other people or society as a whole, such as charitable donations, cooperation, trust, altruistic punishment, and fairness. These behaviors have been widely described through non self-interest decision-making in behavioral experimental studies and are thought to be increased by social preference motives. Importantly, recent studies using a combination of neuroimaging and brain stimulation, designed to reveal the neural mechanisms of pro-social behaviors, have found that a wide range of brain areas, specifically the prefrontal cortex, anterior insula, anterior cingulate cortex, and amygdala, are correlated or causally related with pro-social behaviors. In this review, we summarize the research on the neural basis of various kinds of pro-social behaviors and describe a common shared neural circuitry of these pro-social behaviors. We introduce several general ways in which experimental economics and neuroscience can be combined to develop important contributions to understanding social decision-making and pro-social behaviors. Future research should attempt to explore the neural circuitry between the frontal lobes and deeper brain areas.

  14. Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

    Directory of Open Access Journals (Sweden)

    Daniel Charles Castro

    2015-06-01

    Full Text Available The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc and ventral pallidum (VP, in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (‘liking’ and motivational incentive salience (‘wanting’ of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating versus intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including ‘liking’ and ‘wanting’ for food rewards.

  15. Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury.

    Science.gov (United States)

    Zholudeva, Lyandysha V; Karliner, Jordyn S; Dougherty, Kimberly J; Lane, Michael A

    2017-11-01

    More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. The identity of spinal interneurons involved with respiratory plasticity post-SCI, however, has remained largely unknown. Using a transgenic Chx10-eGFP mouse line (Strain 011391-UCD), the present study is the first to demonstrate the recruitment of excitatory interneurons into injured phrenic circuitry after a high cervical SCI. Diaphragm electromyography and anatomical analysis were used to confirm lesion-induced functional deficits and document extent of the lesion, respectively. Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.

  16. Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

    International Nuclear Information System (INIS)

    Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J.

    2016-01-01

    testis, despite the fact that dmrt1 itself was not different in expression from control males. Transcriptional networks involving forkhead box L2 (foxl2) (transcript involved in ovarian follicle development) were increased in expression in the testis. Noteworthy was that a gene network associated to granulosa cell development was increased over 100%, suggesting that this transcriptome network may be important for monitoring estrogenic exposures. Other cell processes rapidly downregulated by EE2 at the transcript level included glucose homeostasis, response to heavy metal, amino acid catabolism, and the cyclooxygenase pathway. Conversely, lymphocyte chemotaxis, intermediate filament polymerization, glucocorticoid metabolism, carbohydrate utilization, and anterior/posterior axis specification were increased. These data provide new insight into the transcriptional responses that are perturbed prior to gonadal remodeling and intersex following exposure to estrogens. These data demonstrate that low concentrations of EE2 (1) rapidly suppresses male hormone production, (2) down-regulate molecular networks related to male sex differentiation, and (3) induce transcriptional networks related to granulosa cell development in the adult testis. These responses are hypothesized to be key molecular initiating events that occur prior to the development of the intersex phenotype following estrogenic exposures.

  17. Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

    Energy Technology Data Exchange (ETDEWEB)

    Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J., E-mail: cmartyni@yahoo.ca

    2016-12-15

    testis, despite the fact that dmrt1 itself was not different in expression from control males. Transcriptional networks involving forkhead box L2 (foxl2) (transcript involved in ovarian follicle development) were increased in expression in the testis. Noteworthy was that a gene network associated to granulosa cell development was increased over 100%, suggesting that this transcriptome network may be important for monitoring estrogenic exposures. Other cell processes rapidly downregulated by EE2 at the transcript level included glucose homeostasis, response to heavy metal, amino acid catabolism, and the cyclooxygenase pathway. Conversely, lymphocyte chemotaxis, intermediate filament polymerization, glucocorticoid metabolism, carbohydrate utilization, and anterior/posterior axis specification were increased. These data provide new insight into the transcriptional responses that are perturbed prior to gonadal remodeling and intersex following exposure to estrogens. These data demonstrate that low concentrations of EE2 (1) rapidly suppresses male hormone production, (2) down-regulate molecular networks related to male sex differentiation, and (3) induce transcriptional networks related to granulosa cell development in the adult testis. These responses are hypothesized to be key molecular initiating events that occur prior to the development of the intersex phenotype following estrogenic exposures.

  18. DHT inhibits the Aβ25-35-induced apoptosis by regulation of seladin-1, survivin, XIAP, bax, and bcl-xl expression through a rapid PI3-K/Akt signaling in C6 glial cell lines.

    Science.gov (United States)

    Bing, Lelin; Wu, Junfeng; Zhang, Jianfeng; Chen, Yinghui; Hong, Zhen; Zu, Hengbing

    2015-01-01

    Previous evidences indicate that androgen is neuroprotective in the brain. However, the underling mechanisms remain to be fully elucidated. Moreover, it is controversial whether dihydrotestosterone (DHT) modulates the expression of apoptosis-related effectors, such as survivin, XIAP, bax, and bcl-xl proteins mediated by the PI3-K/Akt pathway, which contributes to androgen neuroprotection. In this study using a C6 glial cell model, apoptotic cells were detected by flow cytometry. Akt, seladin-1, survivin, XIAP, bcl-xl, and bax protein expression is investigated by Western blot. After amyloid β-protein fragment (Aβ25-35) treatment, apoptotic cells at early (annexin V+, PI-) and late (annexin V+, PI+) stages were significantly increased. Apoptosis at early and late was obviously inhibited in the presence of DHT. The effect of DHT was markedly blocked by PI3-K inhibitor LY294002.To elicit the mechanism of DHT protection, the expression of seladin-1, survivin, XIAP, bax, and bcl-xl protein was determined in C6 cells treated with Aβ25-35, DHT, or LY294002. Aβ25-35 significantly downregulated the expression of seladin-1, survivin, XIAP, bcl-xl protein and upregulated the expression of bax protein. DHT significantly inhibited the expression of bax, seladin-1, survivin, XIAP, and bcl-xl protein induced by Aβ25-35. Further, we found the effect of DHT was significantly inhibited by LY294002. Collectively, in a C6 glial cell model, we firstly found that DHT inhibits Aβ25-35-induced apoptosis by a rapid nongenic PI-3K/Akt activation as well as regulation of seladin-1, survivin, XIAP, bcl-xl, and bax proteins.

  19. Determining the Control Circuitry of Redox Metabolism at the Genome-Scale

    DEFF Research Database (Denmark)

    Federowicz, Stephen; Kim, Donghyuk; Ebrahim, Ali

    2014-01-01

    -scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes...

  20. Wired for behavior: from development to function of innate limbic system circuitry

    Directory of Open Access Journals (Sweden)

    Katie eSokolowski

    2012-04-01

    Full Text Available The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional or motivational salience, which includes innate behaviors such as mating, aggression and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents, and is then processed in the brain by a set of delineated structures that primarily includes the amygdala and hypothalamus. While the basic neuroanatomy of these connections is well established, much remains unknown about how information is processed within innate circuits and how genetic hierarchies regulate development and function of these circuits. Utilizing innovative technologies including channel rhodopsin-based circuit manipulation and genetic manipulation in rodents, recent studies have begun to answer these central questions. In this article we review the current understanding of how limbic circuits regulate sexually dimorphism and how these circuits are established and shaped during pre- and post-natal development. We also discuss how understanding developmental processes of innate circuit formation may inform behavioral alterations observed in neurodevelopmental disorders, such as autism spectrum disorders, which are characterized by limbic system dysfunction.

  1. A coordinated interdependent protein circuitry stabilizes the kinetochore ensemble to protect CENP-A in the human pathogenic yeast Candida albicans.

    Directory of Open Access Journals (Sweden)

    Jitendra Thakur

    Full Text Available Unlike most eukaryotes, a kinetochore is fully assembled early in the cell cycle in budding yeasts Saccharomyces cerevisiae and Candida albicans. These kinetochores are clustered together throughout the cell cycle. Kinetochore assembly on point centromeres of S. cerevisiae is considered to be a step-wise process that initiates with binding of inner kinetochore proteins on specific centromere DNA sequence motifs. In contrast, kinetochore formation in C. albicans, that carries regional centromeres of 3-5 kb long, has been shown to be a sequence independent but an epigenetically regulated event. In this study, we investigated the process of kinetochore assembly/disassembly in C. albicans. Localization dependence of various kinetochore proteins studied by confocal microscopy and chromatin immunoprecipitation (ChIP assays revealed that assembly of a kinetochore is a highly coordinated and interdependent event. Partial depletion of an essential kinetochore protein affects integrity of the kinetochore cluster. Further protein depletion results in complete collapse of the kinetochore architecture. In addition, GFP-tagged kinetochore proteins confirmed similar time-dependent disintegration upon gradual depletion of an outer kinetochore protein (Dam1. The loss of integrity of a kinetochore formed on centromeric chromatin was demonstrated by reduced binding of CENP-A and CENP-C at the centromeres. Most strikingly, Western blot analysis revealed that gradual depletion of any of these essential kinetochore proteins results in concomitant reduction in cellular protein levels of CENP-A. We further demonstrated that centromere bound CENP-A is protected from the proteosomal mediated degradation. Based on these results, we propose that a coordinated interdependent circuitry of several evolutionarily conserved essential kinetochore proteins ensures integrity of a kinetochore formed on the foundation of CENP-A containing centromeric chromatin.

  2. Determining the control circuitry of redox metabolism at the genome-scale.

    Directory of Open Access Journals (Sweden)

    Stephen Federowicz

    2014-04-01

    Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

  3. Histamine modulation of the basal ganglia circuitry in the development of pathological grooming

    Science.gov (United States)

    Rapanelli, Maximiliano; Frick, Luciana

    2017-01-01

    Aberrant histaminergic function has been proposed as a cause of tic disorders. A rare mutation in the enzyme that produces histamine (HA), histidine decarboxylase (HDC), has been identified in patients with Tourette syndrome (TS). Hdc knockout mice exhibit repetitive behavioral pathology and neurochemical characteristics of TS, establishing them as a plausible model of tic pathophysiology. Where, when, and how HA deficiency produces these effects has remained unclear: whether the contribution of HA deficiency to pathogenesis is acute or developmental, and where in the brain the relevant consequences of HA deficiency occur. Here, we address these key pathophysiological questions, using anatomically and cellularly targeted manipulations in mice. We report that specific ablation or chemogenetic silencing of histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus leads to markedly elevated grooming, a form of repetitive behavioral pathology, and to elevated markers of neuronal activity in both dorsal striatum and medial prefrontal cortex. Infusion of HA directly into the striatum reverses this behavioral pathology, confirming that acute HA deficiency mediates the effect. Bidirectional chemogenetic regulation reveals that dorsal striatum neurons activated after TMN silencing are both sufficient to produce repetitive behavioral pathology and necessary for the full expression of the effect. Chemogenetic activation of TMN-regulated medial prefrontal cortex neurons, in contrast, increases locomotion and not grooming. These data confirm the centrality of striatal regulation by neurotransmitter HA in the adult in the production of pathological grooming. PMID:28584117

  4. Rapid shallow breathing

    Science.gov (United States)

    Tachypnea; Breathing - rapid and shallow; Fast shallow breathing; Respiratory rate - rapid and shallow ... Shallow, rapid breathing has many possible medical causes, including: Asthma Blood clot in an artery in the ...

  5. Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

    Science.gov (United States)

    Mattson, M P; Lee, R E; Adams, M E; Guthrie, P B; Kater, S B

    1988-11-01

    A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

  6. In search of the next memory inside the circuitry from the oldest to the emerging non-volatile memories

    CERN Document Server

    Campardo, Giovanni

    2017-01-01

    This book provides students and practicing chip designers with an easy-to-follow yet thorough, introductory treatment of the most promising emerging memories under development in the industry. Focusing on the chip designer rather than the end user, this book offers expanded, up-to-date coverage of emerging memories circuit design. After an introduction on the old solid-state memories and the fundamental limitations soon to be encountered, the working principle and main technology issues of each of the considered technologies (PCRAM, MRAM, FeRAM, ReRAM) are reviewed and a range of topics related to design is explored: the array organization, sensing and writing circuitry, programming algorithms and error correction techniques are reviewed comparing the approach followed and the constraints for each of the technologies considered. Finally the issue of radiation effects on memory devices has been briefly treated. Additionally some considerations are entertained about how emerging memories can find a place in the...

  7. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the substantiation of a health claim related to Preservation ® and “ rapid recovery of cellular activity post stress ” pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from ICP Ltd, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Malta, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific...... substantiation of a health claim related to Preservation® and “rapid recovery of cellular activity post stress”. The Panel considers that Preservation®, which contains an extract of prickly pear cactus Opuntia ficus-indica, is sufficiently characterised. The claimed effect is “rapid recovery of cellular activity...

  8. All-optical routing and switching for three-dimensional photonic circuitry

    Science.gov (United States)

    Keil, Robert; Heinrich, Matthias; Dreisow, Felix; Pertsch, Thomas; Tünnermann, Andreas; Nolte, Stefan; Christodoulides, Demetrios N.; Szameit, Alexander

    2011-01-01

    The ability to efficiently transmit and rapidly process huge amounts of data has become almost indispensable to our daily lives. It turned out that all-optical networks provide a very promising platform to deal with this task. Within such networks opto-optical switches, where light is directed by light, are a crucial building block for an effective operation. In this article, we present an experimental analysis of the routing and switching behaviour of light in two-dimensional evanescently coupled waveguide arrays of Y- and T-junction geometries directly inscribed into fused silica using ultrashort laser pulses. These systems have the fundamental advantage of supporting three-dimensional network topologies, thereby breaking the limitations on complexity associated with planar structures while maintaining a high dirigibility of the light. Our results show how such arrays can be used to control the flow of optical signals within integrated photonic circuits. PMID:22355612

  9. Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

    Science.gov (United States)

    King, L A; Peterson, D S; Mancini, M; Carlson-Kuhta, P; Fling, B W; Smulders, K; Nutt, J G; Dale, M; Carter, J; Winters-Stone, K M; Horak, F B

    2015-10-24

    There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. This trial is registered at clinical trials.gov (NCT02231073).

  10. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

    Science.gov (United States)

    Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

    2012-01-01

    It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

  11. Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

    Science.gov (United States)

    Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

    2012-01-01

    Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

  12. Circuitry linking the global Csr and σE-dependent cell envelope stress response systems.

    Science.gov (United States)

    Yakhnin, Helen; Aichele, Robert; Ades, Sarah E; Romeo, Tony; Babitzke, Paul

    2017-09-18

    CsrA of Escherichia coli is an RNA-binding protein that globally regulates a wide variety of cellular processes and behaviors including carbon metabolism, motility, biofilm formation, and the stringent response. CsrB and CsrC are sRNAs that sequester CsrA, thereby preventing CsrA-mRNA interaction. RpoE (σ E ) is the extracytoplasmic stress response sigma factor of E. coli Previous RNA-seq studies identified rpoE mRNA as a CsrA target. Here we explored the regulation of rpoE by CsrA and found that CsrA represses rpoE translation. Gel mobility shift, footprint and toeprint studies identified three CsrA binding sites in the rpoE leader transcript, one of which overlaps the rpoE Shine-Dalgarno (SD) sequence, while another overlaps the rpoE translation initiation codon. Coupled in vitro transcription-translation experiments showed that CsrA represses rpoE translation by binding to these sites. We further demonstrate that σ E indirectly activates transcription of csrB and csrC , leading to increased sequestration of CsrA such that repression of rpoE by CsrA is reduced. We propose that the Csr system fine-tunes the σ E -dependent cell envelope stress response. We also identified a 51 amino acid coding sequence whose stop codon overlaps the rpoE start codon, and demonstrate that rpoE is translationally coupled with this upstream open reading frame (ORF51). Loss of coupling reduces rpoE translation by more than 50%. Identification of a translationally coupled ORF upstream of rpoE suggests that this previously unannotated protein may participate in the cell envelope stress response. In keeping with existing nomenclature, we name ORF51 as rseD , resulting in an operon arrangement of rseD-rpoE-rseA-rseB-rseC IMPORTANCE CsrA posttranscriptionally represses genes required for bacterial stress responses, including the stringent response, catabolite repression, and the RpoS (σ S )-mediated general stress response. We show that CsrA represses translation of rpoE , encoding the

  13. Volatile solvents as drugs of abuse: focus on the cortico-mesolimbic circuitry.

    Science.gov (United States)

    Beckley, Jacob T; Woodward, John J

    2013-12-01

    Volatile solvents such as those found in fuels, paints, and thinners are found throughout the world and are used in a variety of industrial applications. However, these compounds are also often intentionally inhaled at high concentrations to produce intoxication. While solvent use has been recognized as a potential drug problem for many years, research on the sites and mechanisms of action of these compounds lags behind that of other drugs of abuse. In this review, we first discuss the epidemiology of voluntary solvent use throughout the world and then consider what is known about their basic pharmacology and how this may explain their use as drugs of abuse. We next present data from preclinical and clinical studies indicating that these substances induce common addiction sequelae such as dependence, withdrawal, and cognitive impairments. We describe how toluene, the most commonly studied psychoactive volatile solvent, alters synaptic transmission in key brain circuits such as the mesolimbic dopamine system and medial prefrontal cortex (mPFC) that are thought to underlie addiction pathology. Finally, we make the case that activity in mPFC circuits is a critical regulator of the mesolimbic dopamine system's ability to respond to volatile solvents like toluene. Overall, this review provides evidence that volatile solvents have high abuse liability because of their selective effects on critical nodes of the addiction neurocircuitry, and underscores the need for more research into how these compounds induce adaptations in neural circuits that underlie addiction pathology.

  14. Abnormal fear circuitry in Attention Deficit Hyperactivity Disorder: A controlled magnetic resonance imaging study.

    Science.gov (United States)

    Spencer, Andrea E; Marin, Marie-France; Milad, Mohammed R; Spencer, Thomas J; Bogucki, Olivia E; Pope, Amanda L; Plasencia, Natalie; Hughes, Brittany; Pace-Schott, Edward F; Fitzgerald, Maura; Uchida, Mai; Biederman, Joseph

    2017-04-30

    We examined whether non-traumatized subjects with Attention Deficit Hyperactivity Disorder (ADHD) have dysfunctional activation in brain structures mediating fear extinction, possibly explaining the statistical association between ADHD and other disorders characterized by aberrant fear processing such as PTSD. Medication naïve, non-traumatized young adult subjects with (N=27) and without (N=20) ADHD underwent a 2-day fear conditioning and extinction protocol in a 3T functional magnetic resonance imaging (fMRI) scanner. Skin conductance response (SCR) was recorded as a measure of conditioned response. Compared to healthy controls, ADHD subjects had significantly greater insular cortex activation during early extinction, lesser dorsal anterior cingulate cortex (dACC) activation during late extinction, lesser ventromedial prefrontal cortex (vmPFC) activation during late extinction learning and extinction recall, and greater hippocampal activation during extinction recall. Hippocampal and vmPFC deficits were similar to those documented in PTSD subjects compared to traumatized controls without PTSD. Non-traumatized, medication naive adults with ADHD had abnormalities in fear circuits during extinction learning and extinction recall, and some findings were consistent with those previously documented in subjects with PTSD compared to traumatized controls without PTSD. These findings could explain the significant association between ADHD and PTSD as well as impaired emotion regulation in ADHD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  15. Design Options for Thermal Shutdown Circuitry with Hysteresis Width Independent on the Activation Temperature

    Directory of Open Access Journals (Sweden)

    PLESA, C.-S.

    2017-02-01

    Full Text Available This paper presents several design options for implementing a thermal shutdown circuit with hysteretic characteristic, which has two special features: a programmable activation temperature (the upper trip point of the characteristic and a hysteresis width largely insensitive to the actual value of the activation temperature and to variations of the supply voltage. A fairly straightforward architecture is employed, with the hysteresis implemented by a current source enabled by the output of the circuit. Four possible designs are considered for this current source: VBE/R, modified-VBE/R, Widlar and a peaking current source tailored for this circuit. First, a detailed analytical analysis of the circuit implemented with these current sources is performed; it indicates the one best suited for this application and provides key sizing equations. Next, the chosen current source is employed to design the thermal shutdown protection of an integrated Low-Dropout Voltage Regulator (LDO for automotive applications. Simulation results and measurements performed on the silicon implementation fully validate the design. Moreover, they compare favorably with the performance of similar circuits reported recently.

  16. Regulatory interactions of stress and reward on rat forebrain opioidergic and GABAergic circuitry.

    Science.gov (United States)

    Christiansen, A M; Herman, J P; Ulrich-Lai, Y M

    2011-03-01

    Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both reward and stress regulation, suggesting that these systems are prime candidates for mediating stress relief by palatable foods. Thus, the present study (1) determines how palatable ?comfort? food alters stress-induced changes in the mRNA expression of inhibitory neurotransmitters in reward and stress neurocircuitry and (2) identifies candidate brain regions that may underlie comfort food-mediated stress reduction. We used a model of palatable ?snacking? in combination with a model of chronic variable stress followed by in situ hybridization to determine forebrain levels of pro-opioid and glutamic acid decarboxylase (GAD) mRNA. The data identify regions within the extended amygdala, striatum, and hypothalamus as potential regions for mediating hypothalamic-pituitary-adrenal axis buffering following palatable snacking. Specifically, palatable snacking alone decreased pro-enkephalin-A (ENK) mRNA expression in the anterior bed nucleus of the stria terminalis (BST) and the nucleus accumbens, and decreased GAD65 mRNA in the posterior BST. Chronic stress alone increased ENK mRNA in the hypothalamus, nucleus accumbens, amygdala, and hippocampus; increased dynorphin mRNA in the nucleus accumbens; increased GAD65 mRNA in the anterior hypothalamus and BST; and decreased GAD65 mRNA in the dorsal hypothalamus. Importantly, palatable food intake prevented stress-induced gene expression changes in subregions of the hypothalamus, BST, and nucleus accumbens. Overall, these data suggest that complex interactions exist between brain reward and stress pathways and that palatable snacking can

  17. Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment.

    Directory of Open Access Journals (Sweden)

    Hui Chen

    Full Text Available OBJECTIVE: Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY and suppressor proopiomelanocortin (POMC in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD consumption are unclear. RESEARCH DESIGN AND METHODS: Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control. At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid metabolic markers were measured. RESULTS: Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. CONCLUSIONS: Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.

  18. Examination of Csr regulatory circuitry using epistasis analysis with RNA-seq (Epi-seq) confirms that CsrD affects gene expression via CsrA, CsrB and CsrC.

    Science.gov (United States)

    Potts, Anastasia H; Leng, Yuanyuan; Babitzke, Paul; Romeo, Tony

    2018-03-29

    The Csr global regulatory system coordinates gene expression in response to metabolic status. This system utilizes the RNA binding protein CsrA to regulate gene expression by binding to transcripts of structural and regulatory genes, thus affecting their structure, stability, translation, and/or transcription elongation. CsrA activity is controlled by sRNAs, CsrB and CsrC, which sequester CsrA away from other transcripts. CsrB/C levels are partly determined by their rates of turnover, which requires CsrD to render them susceptible to RNase E cleavage. Previous epistasis analysis suggested that CsrD affects gene expression through the other Csr components, CsrB/C and CsrA. However, those conclusions were based on a limited analysis of reporters. Here, we reassessed the global behavior of the Csr circuitry using epistasis analysis with RNA seq (Epi-seq). Because CsrD effects on mRNA levels were entirely lost in the csrA mutant and largely eliminated in a csrB/C mutant under our experimental conditions, while the majority of CsrA effects persisted in the absence of csrD, the original model accounts for the global behavior of the Csr system. Our present results also reflect a more nuanced role of CsrA as terminal regulator of the Csr system than has been recognized.

  19. Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain

    Institute of Scientific and Technical Information of China (English)

    Samuel W.Hulbert; Yong-hui Jiang

    2017-01-01

    Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders.Recently,researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time.Thus,a clearer picture is starting to emerge of the cell types,circuits,brain regions,and developmental time periods underlying ASDs.ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons,different neurotransmitter systems,and cells specific to the forebrain or cerebellum.In addition,mutations have been induced or corrected in adult mice,providing some evidence for the plasticity and reversibility of core ASD symptoms.The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism,but other technological advances may eventually overcome this obstacle.

  20. Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation

    Science.gov (United States)

    Blum, K; Oscar-Berman, M; Giordano, J; Downs, BW; Simpatico, T; Han, D; Femino, John

    2012-01-01

    Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies. PMID:23264886

  1. Have we been ignoring the elephant in the room? Seven arguments for considering the cerebellum as part of addiction circuitry.

    Science.gov (United States)

    Miquel, Marta; Vazquez-Sanroman, Dolores; Carbo-Gas, María; Gil-Miravet, Isis; Sanchis-Segura, Carla; Carulli, Daniela; Manzo, Jorge; Coria-Avila, Genaro A

    2016-01-01

    Addiction involves alterations in multiple brain regions that are associated with functions such as memory, motivation and executive control. Indeed, it is now well accepted that addictive drugs produce long-lasting molecular and structural plasticity changes in corticostriatal-limbic loops. However, there are brain regions that might be relevant to addiction other than the prefrontal cortex, amygdala, hippocampus and basal ganglia. In addition to these circuits, a growing amount of data suggests the involvement of the cerebellum in many of the brain functions affected in addicts, though this region has been overlooked, traditionally, in the addiction field. Therefore, in the present review we provide seven arguments as to why we should consider the cerebellum in drug addiction. We present and discuss compelling evidence about the effects of drugs of abuse on cerebellar plasticity, the involvement of the cerebellum in drug-induced cue-related memories, and several findings showing that the instrumental memory and executive functions also recruit the cerebellar circuitry. In addition, a hypothetical model of the cerebellum's role relative to other areas within corticostriatal-limbic networks is also provided. Our goal is not to review animal and human studies exhaustively but to support the inclusion of cerebellar alterations as a part of the physiopathology of addiction disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Bilingualism yields language-specific plasticity in left hemisphere's circuitry for learning to read in young children.

    Science.gov (United States)

    Jasińska, K K; Berens, M S; Kovelman, I; Petitto, L A

    2017-04-01

    How does bilingual exposure impact children's neural circuitry for learning to read? Theories of bilingualism suggests that exposure to two languages may yield a functional and neuroanatomical adaptation to support the learning of two languages (Klein et al., 2014). To test the hypothesis that this neural adaptation may vary as a function of structural and orthographic characteristics of bilinguals' two languages, we compared Spanish-English and French-English bilingual children, and English monolingual children, using functional Near Infrared Spectroscopy neuroimaging (fNIRS, ages 6-10, N =26). Spanish offers consistent sound-to-print correspondences ("phonologically transparent" or "shallow"); such correspondences are more opaque in French and even more opaque in English (which has both transparent and "phonologically opaque" or "deep" correspondences). Consistent with our hypothesis, both French- and Spanish-English bilinguals showed hyperactivation in left posterior temporal regions associated with direct sound-to-print phonological analyses and hypoactivation in left frontal regions associated with assembled phonology analyses. Spanish, but not French, bilinguals showed a similar effect when reading Irregular words. The findings inform theories of bilingual and cross-linguistic literacy acquisition by suggesting that structural characteristics of bilinguals' two languages and their orthographies have a significant impact on children's neuro-cognitive architecture for learning to read. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Palmitoylation regulates 17β-estradiol-induced estrogen receptor-α degradation and transcriptional activity.

    Science.gov (United States)

    La Rosa, Piergiorgio; Pesiri, Valeria; Leclercq, Guy; Marino, Maria; Acconcia, Filippo

    2012-05-01

    The estrogen receptor-α (ERα) is a transcription factor that regulates gene expression through the binding to its cognate hormone 17β-estradiol (E2). ERα transcriptional activity is regulated by E2-evoked 26S proteasome-mediated ERα degradation and ERα serine (S) residue 118 phosphorylation. Furthermore, ERα mediates fast cell responses to E2 through the activation of signaling cascades such as the MAPK/ERK and phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog 1 pathways. These E2 rapid effects require a population of the ERα located at the cell plasma membrane through palmitoylation, a dynamic enzymatic modification mediated by palmitoyl-acyl-transferases. However, whether membrane-initiated and transcriptional ERα activities integrate in a unique picture or represent parallel pathways still remains to be firmly clarified. Hence, we evaluated here the impact of ERα palmitoylation on E2-induced ERα degradation and S118 phosphorylation. The lack of palmitoylation renders ERα more susceptible to E2-dependent degradation, blocks ERα S118 phosphorylation and prevents E2-induced ERα estrogen-responsive element-containing promoter occupancy. Consequently, ERα transcriptional activity is prevented and the receptor addressed to the nuclear matrix subnuclear compartment. These data uncover a circuitry in which receptor palmitoylation links E2-dependent ERα degradation, S118 phosphorylation, and transcriptional activity in a unique molecular mechanism. We propose that rapid E2-dependent signaling could be considered as a prerequisite for ERα transcriptional activity and suggest an integrated model of ERα intracellular signaling where E2-dependent early extranuclear effects control late receptor-dependent nuclear actions.

  4. In Vitro Restoration of an Amyloid-Beta Altered Network Circuitry in a 'Mutated Biomimetic Acetylcholinesterase' Memristor/Memcapacitor Neural Prosthesis

    Directory of Open Access Journals (Sweden)

    John THORNTON

    2015-08-01

    Full Text Available Many diseases involve the ysregulation of acetylcholinesterase (ACHE causing inappropriate production of the neurotransmitter acetylcholine (ACH. Study of how the ACH actually restores a life threatening neural circuitry damage will provide valuable information for study Alzhermer’s disease. An artificial neuronal device was developed with nanostructured biomimetic mutated ACHE gorge membrane on gold chips having memristor/memcapacitor’s characteristics, served as a model for damaged brain circuitry prosthesis, compared before and after ACH treatments, for in vitro evaluation of the memory restoration in the presence of Amyloid-beta (Ab under the conditions of free from tracers and antibodies in NIST human serum. The results are presented in three categories in “Energy-Sensory” images. Before ACH treatments, images showed four stages of circuitry damages from non symptomatic to life threatening. After a 15 nM ACH treatment, the circuitry was restored due to the ACH removed Pathological High Frequency Oscillation (pHFO center during Slow- Waving Sleeping (SWS. After the prosthesis increased hydrophobicity, the High Frequency Oscillation (HFO was created. Results were compared between the recovered and the “normal brain”: 0.14 vs. 0.47 pJ/bit/µm3 for long-term and 14.0 vs.7.0 aJ/bit/µm3 for short-term memory restoration, respectively. The ratio of Rmax/Rmin value is 6.3-fold higher after the treatment of ACH compared without the treatment in the presence of Ab and the reentry sensitivity increased by 613.8- fold.

  5. Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation.

    Science.gov (United States)

    Knight, Emily J; Testini, Paola; Min, Hoon-Ki; Gibson, William S; Gorny, Krzysztof R; Favazza, Christopher P; Felmlee, Joel P; Kim, Inyong; Welker, Kirk M; Clayton, Daniel A; Klassen, Bryan T; Chang, Su-youne; Lee, Kendall H

    2015-06-01

    To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. clinicaltrials.gov Identifier: NCT01809613. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

    Science.gov (United States)

    Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

    2015-01-01

    Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

  7. Regulation of chromatin states by drugs of abuse.

    Science.gov (United States)

    Walker, Deena M; Cates, Hannah M; Heller, Elizabeth A; Nestler, Eric J

    2015-02-01

    Drug addiction involves long-term behavioral abnormalities and gene expression changes throughout the mesolimbic dopamine system. Epigenetic mechanisms establish/maintain alterations in gene expression in the brain, providing the impetus for investigations characterizing how epigenetic processes mediate the effects of drugs of abuse. This review focuses on evidence that epigenetic events, specifically histone modifications, regulate gene expression changes throughout the reward circuitry. Drugs of abuse induce changes in histone modifications throughout the reward circuitry by altering histone-modifying enzymes, manipulation of which reveals a role for histone modification in addiction-related behaviors. There is a complex interplay between these enzymes, resulting in a histone signature of the addicted phenotype. Insights gained from these studies are key to identifying novel targets for diagnosis and therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa.

    Science.gov (United States)

    Frank, Guido K; Shott, Megan E; Hagman, Jennifer O; Mittal, Vijay A

    2013-10-01

    The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. The authors used structural MR imaging to study gray and white matter volumes in women with current restricting-type anorexia nervosa (N=19), women recovered from restricting-type anorexia nervosa (N=24), women with bulimia nervosa (N=19), and healthy comparison women (N=24). All eating disorder groups exhibited increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manual tracing confirmed larger gyrus rectus volume, and volume predicted taste pleasantness ratings across all groups. Analyses also indicated other morphological differences between diagnostic categories. Antero-ventral insula gray matter volumes were increased on the right side in the anorexia nervosa and recovered anorexia nervosa groups and on the left side in the bulimia nervosa group relative to the healthy comparison group. Dorsal striatum volumes were reduced in the recovered anorexia nervosa and bulimia nervosa groups and predicted sensitivity to reward in all three eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas relative to the healthy comparison group. The results held when a range of covariates, such as age, depression, anxiety, and medications, were controlled for. Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value.

  9. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

    Science.gov (United States)

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results and confirmation with additional research and ongoing rodent and human studies of KB220Z, is required. PMID:25526228

  10. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  11. Hybridization of biomedical circuitry

    Science.gov (United States)

    Rinard, G. A.

    1978-01-01

    The design and fabrication of low power hybrid circuits to perform vital signs monitoring are reported. The circuits consist of: (1) clock; (2) ECG amplifier and cardiotachometer signal conditioner; (3) impedance pneumobraph and respiration rate processor; (4) hear/breath rate processor; (5) temperature monitor; and (6) LCD display.

  12. Rapid Tooling via Stereolithography

    OpenAIRE

    Montgomery, Eva

    2006-01-01

    Approximately three years ago, composite stereolithography (SL) resins were introduced to the marketplace, offering performance features beyond what traditional SL resins could offer. In particular, the high heat deflection temperatures and high stiffness of these highly filled resins have opened the door to several new rapid prototyping (RP) applications, including wind tunnel test modelling and, more recently, rapid tooling.

  13. Rapid improvement teams.

    Science.gov (United States)

    Alemi, F; Moore, S; Headrick, L; Neuhauser, D; Hekelman, F; Kizys, N

    1998-03-01

    Suggestions, most of which are supported by empirical studies, are provided on how total quality management (TQM) teams can be used to bring about faster organizationwide improvements. Ideas are offered on how to identify the right problem, have rapid meetings, plan rapidly, collect data rapidly, and make rapid whole-system changes. Suggestions for identifying the right problem include (1) postpone benchmarking when problems are obvious, (2) define the problem in terms of customer experience so as not to blame employees nor embed a solution in the problem statement, (3) communicate with the rest of the organization from the start, (4) state the problem from different perspectives, and (5) break large problems into smaller units. Suggestions for having rapid meetings include (1) choose a nonparticipating facilitator to expedite meetings, (2) meet with each team member before the team meeting, (3) postpone evaluation of ideas, and (4) rethink conclusions of a meeting before acting on them. Suggestions for rapid planning include reducing time spent on flowcharting by focusing on the future, not the present. Suggestions for rapid data collection include (1) sample patients for surveys, (2) rely on numerical estimates by process owners, and (3) plan for rapid data collection. Suggestions for rapid organizationwide implementation include (1) change membership on cross-functional teams, (2) get outside perspectives, (3) use unfolding storyboards, and (4) go beyond self-interest to motivate lasting change in the organization. Additional empirical investigations of time saved as a consequence of the strategies provided are needed. If organizations solve their problems rapidly, fewer unresolved problems may remain.

  14. Rapid pasteurization of shell eggs using RF

    Science.gov (United States)

    A novel method for rapidly pasteurizing eggs in the shell could enhance the safety of the United States’ food supply. Current federal regulations do not require eggs sold in stores to be pasteurized, yet these eggs are often consumed raw or undercooked and cause untold cases of salmonella illness ea...

  15. Rapid response systems.

    Science.gov (United States)

    Lyons, Patrick G; Edelson, Dana P; Churpek, Matthew M

    2018-07-01

    Rapid response systems are commonly employed by hospitals to identify and respond to deteriorating patients outside of the intensive care unit. Controversy exists about the benefits of rapid response systems. We aimed to review the current state of the rapid response literature, including evolving aspects of afferent (risk detection) and efferent (intervention) arms, outcome measurement, process improvement, and implementation. Articles written in English and published in PubMed. Rapid response systems are heterogeneous, with important differences among afferent and efferent arms. Clinically meaningful outcomes may include unexpected mortality, in-hospital cardiac arrest, length of stay, cost, and processes of care at end of life. Both positive and negative interventional studies have been published, although the two largest randomized trials involving rapid response systems - the Medical Early Response and Intervention Trial (MERIT) and the Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients (EPOCH) trial - did not find a mortality benefit with these systems, albeit with important limitations. Advances in monitoring technologies, risk assessment strategies, and behavioral ergonomics may offer opportunities for improvement. Rapid responses may improve some meaningful outcomes, although these findings remain controversial. These systems may also improve care for patients at the end of life. Rapid response systems are expected to continue evolving with novel developments in monitoring technologies, risk prediction informatics, and work in human factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression.

    Directory of Open Access Journals (Sweden)

    Haiyang Geng

    Full Text Available Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD. This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC. Fractional anisotropy (FA values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC region showing significant differences between the two groups was identified.Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

  17. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  18. Rapid world modeling

    International Nuclear Information System (INIS)

    Little, Charles; Jensen, Ken

    2002-01-01

    Sandia National Laboratories has designed and developed systems capable of large-scale, three-dimensional mapping of unstructured environments in near real time. This mapping technique is called rapid world modeling and has proven invaluable when used by prototype systems consisting of sensory detection devices mounted on mobile platforms. These systems can be deployed into previously unmapped environments and transmit real-time 3-D visual images to operators located remotely. This paper covers a brief history of the rapid world modeling system, its implementation on mobile platforms, and the current state of the technology. Applications to the nuclear power industry are discussed. (author)

  19. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on relativistic multiparticle processes in the central rapidity region at asymptotically high energies, a new experimental study of charged K→3π decays, pre-Cherenkov radiation as a phenomenon of 'light barrier', stable S=-2 H dibaryon found in Dubna, calculation of Green functions and gluon top in some unambiguous gauges, a method of a fast selection of inelastic nucleus-nucleus collisions for the CMS experiment and the manifestation of jet quenching in differential distributions of the total transverse energy in nucleus-nucleus collisions

  20. Rapid microbiology - raising awareness.

    Science.gov (United States)

    Bailie, Jonathan

    2016-01-01

    A 'high-level overview' of some of the emerging rapid microbiology technologies designed to help healthcare engineering and infection control teams working in hospitals and other healthcare facilities more rapidly identify potentially hazardous levels of waterborne microorganisms in their water systems, enabling them to take prompt remedial action, and a look at the some of the 'pros and cons' of such testing techniques, was given by Nalco technical director, Howard Barnes, the vice-chair of the Legionella Control Association (LCA), at a recent LCA open day. HEJ editor, Jonathan Bailie, reports.

  1. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on invisible Z-boson width and restrictions on next-to-minimal supersymmetric standard model, cosmic test of honeycomb drift chambers, fission of 209 Bi, 232 Th, 235 U, 238 U and 237 Np in a spallation neutron field, rapid screening of spontaneous and radiation-induced structural changes at the vestigial gene of Drosophila melanogaster by polymerase chain reaction, gamma-ray multiplicities in sub-barrier fission of 226 Th and the decay constants of the scalar and pseudoscalar mesons in the quark models with quasilocal interaction

  2. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    Science.gov (United States)

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  3. AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

    Science.gov (United States)

    Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.

    2014-01-01

    This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  4. Navigate the Digital Rapids

    Science.gov (United States)

    Lindsay, Julie; Davis, Vicki

    2010-01-01

    How can teachers teach digital citizenship when the digital landscape is changing so rapidly? How can teachers teach proper online social interactions when the students are outside their classroom and thus outside their control? Will encouraging students to engage in global collaborative environments land teachers in hot water? These are the…

  5. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  6. Corticostriatal Regulation of Acute Pain

    Directory of Open Access Journals (Sweden)

    Erik Martinez

    2017-05-01

    Full Text Available The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc. This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation.

  7. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  8. Rapidly processable radiographic material

    International Nuclear Information System (INIS)

    Brabandere, L.A. de; Borginon, H.A.; Pattyn, H.A.; Pollet, R.J.

    1981-01-01

    A new rapidly processable radiographic silver halide material is described for use in mammography and non-destructive testing of industrial materials. The radiographic material is used for direct exposure to penetrating radiation without the use of fluorescent-intensifying screens. It consists of a transparent support with a layer of hydrophilic colloid silver halide emulsion on one or both sides. Examples of the preparation of three different silver halide emulsions are given including the use of different chemical sensitizers. These new radiographic materials have good resistance to the formation of pressure marks in rapid processing apparatus and they have improved sensitivity for direct exposure to penetrating radiation compared to conventional radiographic emulsions. (U.K.)

  9. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available for microfluidics K. LAND, S. HUGO, M MBANJWA, L FOURIE CSIR Materials Science and Manufacturing P O Box 395, Pretoria 0001, SOUTH AFRICA Email: kland@csir.co.za INTRODUCTION Microfluidics refers to the manipulation of very small volumes of fluid.... Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  10. Tiber Personal Rapid Transit

    Directory of Open Access Journals (Sweden)

    Diego Carlo D'agostino

    2011-02-01

    Full Text Available The project “Tiber Personal Rapid Transit” have been presented by the author at the Rome City Vision Competition1 2010, an ideas competition, which challenges architects, engineers, designers, students and creatives individuals to develop visionary urban proposals with the intention of stimulating and supporting the contemporary city, in this case Rome. The Tiber PRT proposal tries to answer the competition questions with the definition of a provocative idea: a Personal Rapid transit System on the Tiber river banks. The project is located in the central section of the Tiber river and aims at the renewal of the river banks with the insertion of a Personal Rapid Transit infrastructure. The project area include the riverbank of Tiber from Rome Transtevere RFI station to Piazza del Popolo, an area where main touristic and leisure attractions are located. The intervention area is actually no used by the city users and residents and constitute itself a strong barrier in the heart of the historic city.

  11. Rapid MR imaging

    International Nuclear Information System (INIS)

    Edelman, R.R.; Buxton, R.B.; Brady, T.J.

    1988-01-01

    Conventional magnetic resonance (MR) imaging methods typically require several minutes to produce an image, but the periods of respiration, cardiac motion and peristalsis are on the order of seconds or less. The need to reduce motion artifact, as well as the need to reduce imaging time for patient comfort and efficiency, have provided a strong impetus for the development of rapid imaging methods. For abdominal imaging, motion artifacts due to respiration can be significantly reduced by collecting the entire image during one breath hold. For other applications, such as following the kinetics of administered contrast agents, rapid imaging is essential to achieve adequate time resolution. A shorter imaging time entails a cost in image signal/noise (S/N), but improvements in recent years in magnet homogeneity, gradient and radiofrequency coil design have led to steady improvements in S/N and consequently in image quality. For many chemical applications the available S/N is greater than needed, and a trade-off of lower S/N for a shorter imaging time is acceptable. In this chapter, the authors consider the underlying principles of rapid imaging as well as clinical applications of these methods. The bulk of this review concentrates on short TR imaging, but methods that provide for a more modest decrease in imaging time as well as or those that dramatically shorten the imaging time to tens of milliseconds are also discussed

  12. The Advantages of Human Milk Recognize the Spatiotemporal Locations of Toxins and Intelligently Bypass Them by Forming a Hummingbird-Like Hovering Neural Network Circuitry Based on an Organic Biomimetic Choline Acetyltransferase Memristor/Memcapacitor Prosthesis

    Directory of Open Access Journals (Sweden)

    E. T. CHEN

    2016-08-01

    Full Text Available We have demonstrated a unique approach to study human milk’s advantage in promoting and protecting infant early brain cognitive development by recognizing toxins and intelligently bypassing the toxin by forming high frequency oscillation (HFO in the brain circuitry when compared with organic cow milk samples based on an organic memristor/memcapacitor biomimetic Choline Acetyltransferase (CHAT neural network circuitry prosthesis along with a 3D Energy-sensory dynamic mapping method under antibody- free, radiolabeling-free, and reagent-less conditions. We also demonstrated cow milk is unfit for infant cognitive development, and it is actually harmful in terms of mutating infant brain synapse circuitry conformation, current flow direction, and energy output that lead to multiple Pathological High Frequency Oscillation (pHFO formations, and further, it led to sudden infant death syndrome (SIDS based on our prediction.

  13. Balancing the Basal Ganglia Circuitry: A Possible New Role for Dopamine D2 Receptors in Health and Disease

    OpenAIRE

    Cazorla, Maxime; Kang, Un Jung; Kellendonk, Christoph

    2015-01-01

    Current therapies for treating movement disorders such as Parkinson’s disease are effective but limited by undesirable and intractable side effects. Developing more effective therapies will require better understanding of what causes basal ganglia dys-regulation and why medication-induced side effects develop. Although basal ganglia have been extensively studied in the last decades, its circuit anatomy is very complex, and significant controversy exists as to how the interplay of different ba...

  14. Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa.

    Science.gov (United States)

    Holsen, Laura M; Lawson, Elizabeth A; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K; Klibanski, Anne; Goldstein, Jill M

    2012-09-01

    Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with

  15. Marijuana and cannabinoid regulation of brain reward circuits.

    Science.gov (United States)

    Lupica, Carl R; Riegel, Arthur C; Hoffman, Alexander F

    2004-09-01

    The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

  16. Adipostatic regulation of motivation and emotion.

    Science.gov (United States)

    Davis, Jon F

    2010-05-01

    The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

  17. Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD). An fMRI study.

    Science.gov (United States)

    Jatzko, Alexander; Schmitt, Andrea; Demirakca, Traute; Weimer, Erik; Braus, Dieter F

    2006-03-01

    This study was designed to investigate the circuitry underlying movie-induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI-paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion-related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

  18. Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain

    Science.gov (United States)

    Ferré, S.; Diamond, I.; Goldberg, S.R.; Yao, L.; Hourani, S.M.O.; Huang, Z.L.; Urade, Y.; Kitchen, I.

    2007-01-01

    Adenosine A2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A2A receptors. A2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A2A receptor knockout mice suggest that A2A receptor antagonists might have some therapeutic potential in pain states, in particular where

  19. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on decays of excited strange mesons in the extended NJL model, production of heavy evaporation residues in the reactions induced by an extracted 48 Ca beam on a 208 Pb target, scaling behaviour of tensor analyzing power (A yy ) in the inelastic scattering or relativistic deuterons,two-photon collisions at very low Q 2 from LEP2: forthcoming results, high magnetic field uniformity superconducting magnet for a movable polarized target, multichannel time-to-digital converter for drift detector and wavelet-analysis: application to Gaussian signals

  20. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains eight separate reports on the measurement of charge radii for Ti nuclei, spectroscopy of 13 Be, concentrations of hadrons and quark-gluon plasma in mixed phase, experimental results on one-spin pion asymmetry in the d↑ + A → π±(90 0 ) + X process, new results on cumulative pion and proton production in p-D collisions, investigation of charge exchange reactions, the study of the tensor analyzing power in cumulative particle production on a deuteron beam and an evidence for the excited states of the S = -2 stable light dibaryon. 32 figs., 6 tabs

  1. JINR rapid communications

    International Nuclear Information System (INIS)

    1996-01-01

    The present collection of rapid communications from JINR, Dubna, contains five separate reports on analytic QCD running coupling with finite IR behaviour and universal α bar s (0) value, quark condensate in the interacting pion- nucleon medium at finite temperature and baryon number density, γ-π 0 discrimination with a shower maximum detector using neural networks for the solenoidal tracker at RHIC, off-specular neutron reflection from magnetic media with nondiagonal reflectivity matrices and molecular cytogenetics of radiation-induced gene mutations in Drosophila melanogaster. 21 fig., 1 tab

  2. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on additional conditions on eigenvectors in solving inverse problem for two-dimensional Schroedinger equation, on an absolute calibration of deuteron beam polarization at LHE, determination of the vector component of the polarization of the JINR synchrophasotron deuteron beam, wavelet-analysis: criterion of reliable signal selection, on asymptotics in inclusive production of antinuclei and nuclear fragments, use of neutron activation analysis at the IBR-2 reactor for atmospheric monitoring and impulse method for temperature measurement of silicon detectors

  3. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains six separate reports on Monte Carlo simulation of silicon detectors for the ALICE experiment at LHC, a study of single tagged multihadronic γγ* events at an average Q 2 of 90 GeV 2 , epithermal neutron activation analysis of moss, lichen and pine needles in atmospheric deposition monitoring, the theory of neutrino oscillation, coupled quadrupole and monopole vibrations of large amplitude and test of the Ellis-Jaffe sum rule using parametrization of the measured lepton-proton asymmetry. 21 figs., 18 tabs

  4. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  5. [Study on effects of Corydalis yanhusuo and L-THP on dopamine of reward circuitry in conditioned place preference rats and comparison].

    Science.gov (United States)

    Yu, Shou-Yang; Yang, Pei-Run; Qian, Gang; Wu, Ming-Song; Bai, Wei-Feng; Tu, Ping; Luo, Su-Yuan

    2013-11-01

    To study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects. The CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors. Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

  6. Divergent circuitry underlying food reward and intake effects of ghrelin: dopaminergic VTA-accumbens projection mediates ghrelin's effect on food reward but not food intake.

    Science.gov (United States)

    Skibicka, Karolina P; Shirazi, Rozita H; Rabasa-Papio, Cristina; Alvarez-Crespo, Mayte; Neuber, Corinna; Vogel, Heike; Dickson, Suzanne L

    2013-10-01

    Obesity has reached global epidemic proportions and creating an urgent need to understand mechanisms underlying excessive and uncontrolled food intake. Ghrelin, the only known circulating orexigenic hormone, potently increases food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic reward system and to the increased food reward behavior remains unclear. Here we examine whether VTA-NAc dopaminergic signaling is required for the effects of ghrelin on food reward and intake. In addition, we examine the possibility of endogenous ghrelin acting on the VTA-NAc dopamine neurons. A D1-like or a D2 receptor antagonist was injected into the NAc in combination with ghrelin microinjection into the VTA to investigate whether this blockade attenuates ghrelin-induced food reward behavior. VTA injections of ghrelin produced a significant increase in food motivation/reward behavior, as measured by sucrose-induced progressive ratio operant conditioning, and chow intake. Pretreatment with either a D1-like or D2 receptor antagonist into the NAc, completely blocked the reward effect of ghrelin, leaving chow intake intact. We also found that this circuit is potentially relevant for the effects of endogenously released ghrelin as both antagonists reduced fasting (a state of high circulating levels of ghrelin) elevated sucrose-motivated behavior but not chow hyperphagia. Taken together our data identify the VTA to NAc dopaminergic projections, along with D1-like and D2 receptors in the NAc, as essential elements of the ghrelin responsive circuits controlling food reward behavior. Interestingly results also suggest that food reward behavior and simple intake of chow are controlled by divergent circuitry, where NAc dopamine plays an important role in food reward but not in food intake. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

    Science.gov (United States)

    Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

    2017-02-01

    Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Neurocognitive and electrophysiological evidence of altered face processing in parents of children with autism: implications for a model of abnormal development of social brain circuitry in autism.

    Science.gov (United States)

    Dawson, Geraldine; Webb, Sara Jane; Wijsman, Ellen; Schellenberg, Gerard; Estes, Annette; Munson, Jeffrey; Faja, Susan

    2005-01-01

    Neuroimaging and behavioral studies have shown that children and adults with autism have impaired face recognition. Individuals with autism also exhibit atypical event-related brain potentials to faces, characterized by a failure to show a negative component (N170) latency advantage to face compared to nonface stimuli and a bilateral, rather than right lateralized, pattern of N170 distribution. In this report, performance by 143 parents of children with autism on standardized verbal, visual-spatial, and face recognition tasks was examined. It was found that parents of children with autism exhibited a significant decrement in face recognition ability relative to their verbal and visual spatial abilities. Event-related brain potentials to face and nonface stimuli were examined in 21 parents of children with autism and 21 control adults. Parents of children with autism showed an atypical event-related potential response to faces, which mirrored the pattern shown by children and adults with autism. These results raise the possibility that face processing might be a functional trait marker of genetic susceptibility to autism. Discussion focuses on hypotheses regarding the neurodevelopmental and genetic basis of altered face processing in autism. A general model of the normal emergence of social brain circuitry in the first year of life is proposed, followed by a discussion of how the trajectory of normal development of social brain circuitry, including cortical specialization for face processing, is altered in individuals with autism. The hypothesis that genetic-mediated dysfunction of the dopamine reward system, especially its functioning in social contexts, might account for altered face processing in individuals with autism and their relatives is discussed.

  9. Exposure to Glycolytic Carbon Sources Reveals a Novel Layer of Regulation for the MalT Regulon

    Directory of Open Access Journals (Sweden)

    Sylvia A. Reimann

    2011-01-01

    Full Text Available Bacteria adapt to changing environments by means of tightly coordinated regulatory circuits. The use of synthetic lethality, a genetic phenomenon in which the combination of two nonlethal mutations causes cell death, facilitates identification and study of such circuitry. In this study, we show that the E. coli ompR malTcon double mutant exhibits a synthetic lethal phenotype that is environmentally conditional. MalTcon, the constitutively active form of the maltose system regulator MalT, causes elevated expression of the outer membrane porin LamB, which leads to death in the absence of the osmoregulator OmpR. However, the presence and metabolism of glycolytic carbon sources, such as sorbitol, promotes viability and unveils a novel layer of regulation within the complex circuitry that controls maltose transport and metabolism.

  10. High voltage dc-dc converter with dynamic voltage regulation and decoupling during load-generated arcs

    Science.gov (United States)

    Shimer, Daniel W.; Lange, Arnold C.

    1995-01-01

    A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules.

  11. High voltage dc--dc converter with dynamic voltage regulation and decoupling during load-generated arcs

    Science.gov (United States)

    Shimer, D.W.; Lange, A.C.

    1995-05-23

    A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules. 5 Figs.

  12. Rapid Geophysical Surveyor

    International Nuclear Information System (INIS)

    Roybal, L.G.; Carpenter, G.S.; Josten, N.E.

    1993-01-01

    The Rapid Geophysical Surveyor (RGS) is a system designed to rapidly and economically collect closely-spaced geophysical data used for characterization of US Department of Energy waste sites. Geophysical surveys of waste sites are an important first step in the remediation and closure of these sites; especially older sites where historical records are inaccurate and survey benchmarks have changed because of refinements in coordinate controls and datum changes. Closely-spaced data are required to adequately differentiate pits, trenches, and soil vault rows whose edges may be only a few feet from each other. A prototype vehicle designed to collect magnetic field data was built at the Idaho National Engineering Laboratory (INEL) during the summer of 1992. The RGS was funded by the Buried Waste Integrated Demonstration program. This vehicle was demonstrated at the Subsurface Disposal Area (SDA) within the Radioactive Waste Management Complex at the INEL in September 1992. Magnetic data were collected over two areas in the SDA, with a total survey area of about 1.7 acres. Data were collected at a nominal density of 2 1/2 in. along survey lines spaced 1-ft apart. Over 350,000 data points were collected over a 6 day period corresponding to about 185 worker-days using conventional ground survey techniques

  13. Rapid automated nuclear chemistry

    International Nuclear Information System (INIS)

    Meyer, R.A.

    1979-01-01

    Rapid Automated Nuclear Chemistry (RANC) can be thought of as the Z-separation of Neutron-rich Isotopes by Automated Methods. The range of RANC studies of fission and its products is large. In a sense, the studies can be categorized into various energy ranges from the highest where the fission process and particle emission are considered, to low energies where nuclear dynamics are being explored. This paper presents a table which gives examples of current research using RANC on fission and fission products. The remainder of this text is divided into three parts. The first contains a discussion of the chemical methods available for the fission product elements, the second describes the major techniques, and in the last section, examples of recent results are discussed as illustrations of the use of RANC

  14. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, DUBNA, contains eight separate records on symmetry in modern physics (dedicated to the 100th anniversary of the birth of academician V.A.Fock), the double φ-meson production investigation on the Serpukhov accelerator, two-leptonic η-meson decays and SUSY without R parity, charge form factors and alpha-cluster internal structure of 12 C, increasing of muon-track reconstruction efficiency in ME1/1 Dubna prototype for the CMS/LHC, study of photon-structure function F 2 γ in the reaction e + e - → e + e - + hadrons at LEP2, jets reconstruction possibility in pAu and AuAu interactions at STAR RHIC and high-vacuum nondispersable gas absorber

  15. Rapid thermal pulse annealing

    International Nuclear Information System (INIS)

    Miller, M.G.; Koehn, B.W.; Chaplin, R.L.

    1976-01-01

    Characteristics of recovery processes have been investigated for cases of heating a sample to successively higher temperatures by means of isochronal annealing or by using a rapid pulse annealing. A recovery spectra shows the same features independent of which annealing procedure is used. In order to determine which technique provides the best resolution, a study was made of how two independent first-order processes are separated for different heating rates and time increments of the annealing pulses. It is shown that the pulse anneal method offers definite advantages over isochronal annealing when annealing for short time increments. Experimental data by means of the pulse anneal techniques are given for the various substages of stage I of aluminium. (author)

  16. JINR rapid communications

    International Nuclear Information System (INIS)

    1996-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate reports on the identification of events with a secondary vertex in the experiment EXCHARM, the zero degree calorimeter for CERN WA-98 experiment, a new approach to increase the resource of installation elements for super-high energy physics, a method of the in-flight production of exotic systems in the charge-exchange reactions, the neutron activation analysis for monitoring northern terrestrial ecosystems, a search for 28 O and study of the neutron-rich nuclei near the neutron closure N=20, a search for new neutron-rich nuclei with a 70A MeV 48 Ca beam. 33 figs., 4 tabs

  17. JINR Rapid Communications. Collection

    International Nuclear Information System (INIS)

    1994-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on quasi-classical description of one-nucleon transfer reactions with heavy ions, elastic and inelastic scattering in the high energy approximation, experimental study of fission and evaporation cross sections for 6 He + 209 Bi reaction, d ↑ + 12 C → p + X at Θ p = 0 o in the region of high internal momenta in the deuteron, the Nuclotron internal targets, actively screened superconducting magnets, using of polarized target in backward elastic dp scattering, application of transputers in the data acquisition system of the INESS-ALPHA spectrometer, narrow dibaryon resonances with isotopic spin I=2. 93 refs., 27 figs., 4 tabs

  18. JINR Rapid Communications. Collection

    International Nuclear Information System (INIS)

    1994-01-01

    The present collection of rapid communications from JINR, Dubna, contains eight separate reports on Lorentz transformations with superluminal velocities, photo chromic effect in HTSC films, the investigation of hypernuclei in the Nuclotron accelerator, a new hadron jets finding algorithm in the four-dimensional velocity space, investigations of neutral particle production by relativistic nuclei on the LHE 90-channel γ-spectrometer (results and perspectives), coherent meson production in the dp → 3 HeX reaction, the relativistic projectile nuclei fragmentation and A-dependence of nucleon Fermi-momenta, energy spectra of γ-quanta from d-propane interactions at momentum P d = 1.25 GeV/c per nucleon. 86 refs., 26 figs., 4 tabs

  19. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on measurements of the total cross section difference Δσ L (np) at 1.59, 1.79, and 2.20 GeV, to the estimation of angular distributions of double charged spectator fragments in nucleus-nucleus interactions at superhigh energies, simulation dE/dx analysis results for silicon inner tracking system of ALICE set-up at LHC accelerator, high-multiplicity processes, triggering of high-multiplicity events using calorimetry, ORBIT-3.0 - a computer code for simulation and correction of the closed orbit and first turn in synchrotrons and determination of memory performance

  20. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on yields of the rare-earth neutron-deficient isotopes in the reactions of Mo isotopes with 40 Ca ions, observations of slow components of solitonic-type wave structure excited by e-beam in massive copper sample, development and investigation of low-mass multilayer drift chambers (MDC-2) for inner part of the HADES spectrometer, temperature measurement of the uranium sample irradiated with secondary neutrons, edge effects in multiwire proportional chambers, the influence of the dielectric frame, an object-oriented framework for the hadronic Monte-Carlo event generators and uranium-238 as a source for electronuclear power production. 32 figs., 3 tabs

  1. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on collective energy dissipation and fluctuations in elastoplastic systems, diagnostics system of the circulating beam of the NUCLOTRON based on microchannel plates, time-of-flight detector for WA98 CERN experiment, fractal structure formation on the surfaces of solids subjected to high intensity electron and ion treatment, production of nuclei in 32,34,36 S-induced reactions in the energy range 6-75 MeV/A, rare-earth elements in soil and pine needle from northern terrestrial ecosystems, 'thermal' multifragmentation in p + Au collisions at relativistic energies, search for effects of the OZI rule violation in φ and ω mesons production in polarized deuteron beam interaction with polarized proton target (project DPHE3) and fast detector for triggering on charged particle multiplicity for relativistic nucleus-nucleus collisions

  2. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate reports on observation of transversal handedness in the diffractive production of pion triples, a possible experiment on the research of dibaryon states, Cherenkov beam counter system of the CERES/NA45 spectrometer for investigation with 160 GeV/n. lead ions, a profile-based gaseous detector with capacitive pad readout as the prototype of the shower maximum detector for the end-cap electromagnetic calorimeter for the STAR experiment, what DELPHI can get with an upgraded position for the very small angle tagger, estimation of the radiation environment and the shielding aspect for the point 2 area of the LHC and the orthopositronium decay puzzle

  3. Rapid chemical separations

    CERN Document Server

    Trautmann, N

    1976-01-01

    A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

  4. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate reports on investigation of the tensor analyzing power A yy in the reaction A(d polarized, p)X at large transverse momenta of proton, double-differential ionization cross section calculations for fast collisions of ions and atoms, a study of the two-photon interactions tagged at an average 2 > of 90 GeV 2 , cluster and single-particle distributions in nucleus-nucleus interactions, the Coulomb interaction of charged pions in CC-and CTa-collisions at 4.2 A GeV/c, influence of nitrogen and oxygen gas admixtures on the response of the DELPHI HCAL and MUS detectors and an automation of physics research on base of open standards

  5. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on effects arising from charged particles overcoming of the light velocity barrier, deformable templates for circle recognition, scintillation detectors for precise time measurements, atomic form factors and incoherent scattering functions of atoms and ions with the number of electrons N ≤ 10, experimental set-up ANOMALON for measurement of relativistic nuclear fragmentation cross sections, superconducting dipole magnet for ALICE dimuon arm spectrometer, analysis of transverse mass dependence of Bose-Einstein correlation radii using the DELPHI data, low-energy theorem in softly broken supersymmetry and study of the characteristics of particles in reactions π - , p, d, He, C + C with the total disintegration on carbon nucleus

  6. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains six separate records on test of a threshold aerogel Cherenkov counter on cosmic particles, first results of study of transversal dimension of region of cumulative particles production in d + C and d + Cu reactions for energy 2 GeV/nucleon, the evidence of σ[0 + (0 ++ 0)] meson at a mass of M π + π - = 750 ± 5 MeV/c 2 observed in π + π - combinations from the reaction np → npπ + π - at an incident momentum of P n (5.20 ± 0.16 GeV/c, inclusive spectra of protons and π - mesons emitted in 4 HeC and 12 CC interactions with total disintegration of nuclei, heavy quark-antiquark pair production by double pomeron exchange in pp and AA collisions on the CMS and global features of nucleus-nucleus collisions in ultrarelativistic domain

  7. Rapid Refresh (RAP) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  8. Rapid Refresh (RAP) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  9. Rapid population growth.

    Science.gov (United States)

    1972-01-01

    At the current rate of population growth, world population by 2000 is expected to reach 7 billion or more, with developing countries accounting for some 5.4 billion, and economically advanced nations accounting for 1.6 billion. 'Population explosion' is the result of falling mortality rates and continuing high birth rates. Many European countries, and Japan, have already completed what is termed as demographic transition, that is, birth rates have fallen to below 20 births per 1000 population, death rates to 10/1000 population, and annual growth rates are 1% or less; annual growth rates for less developed countries ranged from 2 to 3.5%. Less developed countries can be divided into 3 groups: 1) countries with both high birth and death rates; 2) countries with high birth rates and low death rates; and 3) countries with intermediate and declining birth rates and low death rates. Rapid population growth has serious economic consequences. It encourages inequities in income distribution; it limits rate of growth of gross national product by holding down level of savings and capital investments; it exerts pressure on agricultural production and land; and it creates unemployment problems. In addition, the quality of education for increasing number of chidren is adversely affected, as high proportions of children reduce the amount that can be spent for the education of each child out of the educational budget; the cost and adequacy of health and welfare services are affected in a similar way. Other serious consequences of rapid population growth are maternal death and illness, and physical and mental retardation of children of very poor families. It is very urgent that over a billion births be prevented in the next 30 years to reduce annual population growth rate from the current 2% to 1% per year.

  10. Rapid geophysical surveyor

    International Nuclear Information System (INIS)

    Roybal, L.G.; Carpenter, G.S.; Josten, N.E.

    1993-01-01

    The Rapid Geophysical Surveyor (RGS) is a system designed to rapidly and economically collect closely-spaced geophysical data used for characterization of Department of Energy (DOE) waste sites. Geophysical surveys of waste sites are an important first step in the remediation and closure of these sites; especially older sties where historical records are inaccurate and survey benchmarks have changed due to refinements in coordinate controls and datum changes. Closely-spaced data are required to adequately differentiate pits, trenches, and soil vault rows whose edges may be only a few feet from each other. A prototype vehicle designed to collect magnetic field data was built at the Idaho national Engineering Laboratory (INEL) during the summer of 1992. The RGS was one of several projects funded by the Buried Waste Integrated Demonstration (BWID) program. This vehicle was demonstrated at the Subsurface Disposal Area (SDA) within the Radioactive Waste Management Complex (RWMC) on the INEL in September of 1992. Magnetic data were collected over two areas in the SDA, with a total survey area of about 1.7 acres. Data were collected at a nominal density of 2 1/2 inches along survey lines spaced 1 foot apart. Over 350,000 data points were collected over a 6 day period corresponding to about 185 man-days using conventional ground survey techniques. This report documents the design and demonstration of the RGS concept including the presentation of magnetic data collected at the SDA. The surveys were able to show pit and trench boundaries and determine details of their spatial orientation never before achieved

  11. Rapid Evaporation of microbubbles

    Science.gov (United States)

    Gautam, Jitendra; Esmaeeli, Asghar

    2008-11-01

    When a liquid is heated to a temperature far above its boiling point, it evaporates abruptly. Boiling of liquid at high temperatures can be explosive and destructive, and poses a potential hazard for a host of industrial processes. Explosive boiling may occur if a cold and volatile liquid is brought into contact with a hot and non-volatile liquid, or if a liquid is superheated or depressurized rapidly. Such possibilities are realized, for example, in the depressurization of low boiling point liquefied natural gas (LNG) in the pipelines or storage tanks as a result of a leak. While boiling of highly heated liquids can be destructive at macroscale, the (nearly) instantaneous pace of the process and the release of large amount of kinetic energy make the phenomena extremely attractive at microscale where it is possible to utilize the released energy to derive micromechanical systems. For instance, there is currently a growing interest in micro-explosion of liquid for generation of micro bubbles for actuation purposes. The aim of the current study is to gain a fundamental understanding of the subject using direct numerical simulations. In particular, we seek to investigate the boundary between stable and unstable nucleus growth in terms of the degree of liquid superheat and to compare the dynamics of unstable and stable growth.

  12. Rapid flow imaging method

    International Nuclear Information System (INIS)

    Pelc, N.J.; Spritzer, C.E.; Lee, J.N.

    1988-01-01

    A rapid, phase-contrast, MR imaging method of imaging flow has been implemented. The method, called VIGRE (velocity imaging with gradient recalled echoes), consists of two interleaved, narrow flip angle, gradient-recalled acquisitions. One is flow compensated while the second has a specified flow encoding (both peak velocity and direction) that causes signals to contain additional phase in proportion to velocity in the specified direction. Complex image data from the first acquisition are used as a phase reference for the second, yielding immunity from phase accumulation due to causes other than motion. Images with pixel values equal to MΔΘ where M is the magnitude of the flow compensated image and ΔΘ is the phase difference at the pixel, are produced. The magnitude weighting provides additional vessel contrast, suppresses background noise, maintains the flow direction information, and still allows quantitative data to be retrieved. The method has been validated with phantoms and is undergoing initial clinical evaluation. Early results are extremely encouraging

  13. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains twelve separate reports on an estimation of the possibility of fusion reactions in water molecules, an analysis of pion spectra of the charge-exchange reaction Mg(t, 3 He), the results of simulation of e + e - pair production and detection in the ALICE experiment, the data on the edge effects in multiwire proportional chambers, standard and nonstandard applications of wavelet analysis, the design and study of light readout system for scintillator shower maximum detector for the endcap electromagnetic calorimeter for the STAR experiment at RHIC, a study of multiparticle azimuthal correlations in high energy interactions, coherent multifragmentation of relativistic nuclei, superposition of neutrino eigenstates and neutrino oscillation, simulation results and suggestions for possible design of gaseous shower maximum detector for the endcap electromagnetic calorimeter for the STAR experiment at RHIC, determination of the sizes of the pion emission region in np-interactions at P n =(5.2±0.16)GeV/c using the interference correlation method for identical particles, inelasticity of nucleus-nucleus collisions in the CMS experiment. 65 figs., 19 tabs

  14. Rapid Polymer Sequencer

    Science.gov (United States)

    Stolc, Viktor (Inventor); Brock, Matthew W (Inventor)

    2013-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal direction, or in a transverse direction, in the tip region, a polymer sequence is passed through the tip region, and a change in an electrical current signal is measured as each polymer component passes through the tip region. Each of the measured changes in electrical current signals is compared with a database of reference electrical change signals, with each reference signal corresponding to an identified polymer component, to identify the unknown polymer component with a reference polymer component. The nanopore preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  15. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program.

    Science.gov (United States)

    Hindi, Sajedah M; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M; Ogura, Yuji; Yan, Zhen; Burkly, Linda C; Zheng, Timothy S; Kumar, Ashok

    2014-03-01

    Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.

  16. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie

    2015-08-27

    © 2015 Taylor & Francis Group, LLC. Abscisic acid (ABA) is a major phytohormone mediating important stress-related processes. We recently unveiled an ABA-activated MAPK signaling module constituted of MAP3K17/18-MKK3-MPK1/2/7/14. Unlike classical rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests that MAPKs can regulate both early and longterm plant stress responses.

  17. Radiation regulation

    International Nuclear Information System (INIS)

    Braithwaite, J.; Grabosky, P.

    1985-01-01

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  18. Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala–BNST connectivity during periods of threat vs safety

    Science.gov (United States)

    Muftuler, L Tugan; Larson, Christine L

    2018-01-01

    Abstract Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants’ self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala–BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. PMID:29126127

  19. Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala-BNST connectivity during periods of threat vs safety.

    Science.gov (United States)

    Pedersen, Walker S; Muftuler, L Tugan; Larson, Christine L

    2018-01-01

    Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants' self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala-BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. © The Author (2017). Published by Oxford University Press.

  20. Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study.

    Science.gov (United States)

    Hardee, Jillian E; Cope, Lora M; Munier, Emily C; Welsh, Robert C; Zucker, Robert A; Heitzeg, Mary M

    2017-06-01

    There is substantial evidence for behavioral sex differences in risk trajectories for alcohol and substance use, with internalizing factors such as negative affectivity contributing more to female risk. Because the neural development of emotion circuitry varies between males and females across adolescence, it represents a potential mechanism by which underlying neurobiology contributes to risk for substance use. Longitudinal functional magnetic resonance imaging was conducted in males and females (n = 18 each) with a family history of alcohol use disorders starting at ages 8-13 years. Participants performed an affective word task during functional magnetic resonance imaging at 1- to 2-year intervals, covering the age range of 8.5-17.6 years (3-4 scans per participant). Significant age-related sex differences were found in the right amygdala and right precentral gyrus for the negative vs neutral word condition. Males showed a significant decrease in both amygdala and precentral gyrus activation with age, whereas the response in females persisted. The subjective experience of internalizing symptomatology significantly increased with age for females but not for males. Taken together, these results reveal sex differences in negative affect processing in at-risk adolescents, and offer longitudinal neural evidence for female substance use risk through internalizing pathways. © The Author (2017). Published by Oxford University Press.

  1. What happens in the thymus does not stay in the thymus: how T cells recycle the CD4+-CD8+ lineage commitment transcriptional circuitry to control their function

    Science.gov (United States)

    Vacchio, Melanie S.; Bosselut, Rémy

    2016-01-01

    MHC-restricted CD4+ and CD8+ T cell are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. While the transcriptional control of CD4+-CD8+ lineage choice in the thymus is now better understood, less was known about what maintains the CD4+- and CD8+-lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in post-thymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4+-CD8+ lineage commitment in the thymus, is critical for CD4+ T cell helper functions. PMID:27260768

  2. An evolution-based strategy for engineering allosteric regulation

    Science.gov (United States)

    Pincus, David; Resnekov, Orna; Reynolds, Kimberly A.

    2017-04-01

    Allosteric regulation provides a way to control protein activity at the time scale of milliseconds to seconds inside the cell. An ability to engineer synthetic allosteric systems would be of practical utility for the development of novel biosensors, creation of synthetic cell signaling pathways, and design of small molecule pharmaceuticals with regulatory impact. To this end, we outline a general approach—termed rational engineering of allostery at conserved hotspots (REACH)—to introduce novel regulation into a protein of interest by exploiting latent allostery that has been hard-wired by evolution into its structure. REACH entails the use of statistical coupling analysis (SCA) to identify ‘allosteric hotspots’ on protein surfaces, the development and implementation of experimental assays to test hotspots for functionality, and a toolkit of allosteric modulators to impinge on endogenous cellular circuitry. REACH can be broadly applied to rewire cellular processes to respond to novel inputs.

  3. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

    Science.gov (United States)

    Arnsten, Amy F T; Rubia, Katya

    2012-04-01

    This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence

  4. Rapid prototyping: een veelbelovende methode

    NARCIS (Netherlands)

    Haverman, T.M.; Karagozoglu, K.H.; Prins, H.; Schulten, E.A.J.M.; Forouzanfar, T.

    2013-01-01

    Rapid prototyping is a method which makes it possible to produce a three-dimensional model based on two-dimensional imaging. Various rapid prototyping methods are available for modelling, such as stereolithography, selective laser sintering, direct laser metal sintering, two-photon polymerization,

  5. Regulative environmental policy. Regulative Umweltpolitik

    Energy Technology Data Exchange (ETDEWEB)

    Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

    1991-01-01

    Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

  6. How Rapid is Rapid Prototyping? Analysis of ESPADON Programme Results

    Directory of Open Access Journals (Sweden)

    Ian D. Alston

    2003-05-01

    Full Text Available New methodologies, engineering processes, and support environments are beginning to emerge for embedded signal processing systems. The main objectives are to enable defence industry to field state-of-the-art products in less time and with lower costs, including retrofits and upgrades, based predominately on commercial off the shelf (COTS components and the model-year concept. One of the cornerstones of the new methodologies is the concept of rapid prototyping. This is the ability to rapidly and seamlessly move from functional design to the architectural design to the implementation, through automatic code generation tools, onto real-time COTS test beds. In this paper, we try to quantify the term “rapid” and provide results, the metrics, from two independent benchmarks, a radar and sonar beamforming application subset. The metrics show that the rapid prototyping process may be sixteen times faster than a conventional process.

  7. Sixth Warren K. Sinclair keynote address: The role of a strong regulator in safe and secure nuclear energy.

    Science.gov (United States)

    Lyons, Peter B

    2011-01-01

    The history of nuclear regulation is briefly reviewed to underscore the early recognition that independence of the regulator was essential in achieving and maintaining public credibility. The current licensing process is reviewed along with the status of applications. Challenges faced by both the NRC and the industry are reviewed, such as new construction techniques involving modular construction, digital controls replacing analog circuitry, globalization of the entire supply chain, and increased security requirements. The vital area of safety culture is discussed in some detail, and its importance is emphasized. Copyright © 2010 Health Physics Society

  8. Manganese-enhanced magnetic resonance imaging (MEMRI) reveals brain circuitry involved in responding to an acute novel stress in rats with a history of repeated social stress.

    Science.gov (United States)

    Bangasser, Debra A; Lee, Catherine S; Cook, Philip A; Gee, James C; Bhatnagar, Seema; Valentino, Rita J

    2013-10-02

    Responses to acute stressors are determined in part by stress history. For example, a history of chronic stress results in facilitated responses to a novel stressor and this facilitation is considered to be adaptive. We previously demonstrated that repeated exposure of rats to the resident-intruder model of social stress results in the emergence of two subpopulations that are characterized by different coping responses to stress. The submissive subpopulation failed to show facilitation to a novel stressor and developed a passive strategy in the Porsolt forced swim test. Because a passive stress coping response has been implicated in the propensity to develop certain psychiatric disorders, understanding the unique circuitry engaged by exposure to a novel stressor in these subpopulations would advance our understanding of the etiology of stress-related pathology. An ex vivo functional imaging technique, manganese-enhanced magnetic resonance imaging (MEMRI), was used to identify and distinguish brain regions that are differentially activated by an acute swim stress (15 min) in rats with a history of social stress compared to controls. Specifically, Mn(2+) was administered intracerebroventricularly prior to swim stress and brains were later imaged ex vivo to reveal activated structures. When compared to controls, all rats with a history of social stress showed greater activation in specific striatal, hippocampal, hypothalamic, and midbrain regions. The submissive subpopulation of rats was further distinguished by significantly greater activation in amygdala, bed nucleus of the stria terminalis, and septum, suggesting that these regions may form a circuit mediating responses to novel stress in individuals that adopt passive coping strategies. The finding that different circuits are engaged by a novel stressor in the two subpopulations of rats exposed to social stress implicates a role for these circuits in determining individual strategies for responding to stressors

  9. 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.

  10. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  11. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  12. 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.

  13. Original circuitry for TOHR tomograph

    International Nuclear Information System (INIS)

    Cuzon, J.C.; Pinot, L.

    1999-01-01

    Having industrialization in mind, a specific electronics for a high resolution tomograph is designed out of the usual standards of nuclear physics. All the information are converted in the time domain and a fast processor, in front of the data acquisition, carries out the time and energy coincidences. (authors)

  14. 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.

  15. UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

    Science.gov (United States)

    Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

    2016-02-25

    The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

    Science.gov (United States)

    Liu, Gang; Chandra, Govind; Niu, Guoqing

    2013-01-01

    SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

  17. Rapid deployment intrusion detection system

    International Nuclear Information System (INIS)

    Graham, R.H.

    1997-01-01

    A rapidly deployable security system is one that provides intrusion detection, assessment, communications, and annunciation capabilities; is easy to install and configure; can be rapidly deployed, and is reusable. A rapidly deployable intrusion detection system (RADIDS) has many potential applications within the DOE Complex: back-up protection for failed zones in a perimeter intrusion detection and assessment system, intrusion detection and assessment capabilities in temporary locations, protection of assets during Complex reconfiguration, and protection in hazardous locations, protection of assets during Complex reconfiguration, and protection in hazardous locations. Many DOE user-need documents have indicated an interest in a rapidly deployable intrusion detection system. The purpose of the RADIDS project is to design, develop, and implement such a system. 2 figs

  18. Rapid Continuous Multimaterial Extrusion Bioprinting

    NARCIS (Netherlands)

    Liu, Wanjun; Zhang, Yu Shrike; Heinrich, Marcel A.; De Ferrari, F; Jang, HL; Bakht, SM; Alvarez, MM; Yang, J; Li, YC; Trujillo-de Stantiago, G; Miri, AK; Zhu, K; Khoshakhlagh, P; Prakash, G; Cheng, H; Guan, X; Zhong, Z; Ju, J; Zhu, GH; Jin, X; Ryon Shin, Su; Dokmeci, M.R.; Khademhosseini, Ali

    The development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled

  19. Colour reconnections and rapidity gaps

    International Nuclear Information System (INIS)

    Loennblad, Leif

    1996-01-01

    I argue that the success of recently proposed models describing events with large rapidity gaps in DIS at HERA in terms of non-perturbative colour exchange is heavily reliant on suppression of perturbative gluon emission in the proton direction. There is little or no physical motivation for such suppression and I show that a model without this suppression cannot describe the rapidity gap events at HERA. (author)

  20. Dilepton distributions at backward rapidities

    International Nuclear Information System (INIS)

    Betemps, M. A.; Ducati, M. B. Gay; Oliveira, E. G. de

    2006-01-01

    The dilepton production at backward rapidities in pAu and pp collisions at RHIC and LHC energies is investigated in the dipole approach. The results are shown through the nuclear modification ratio R pA considering transverse momentum and rapidity spectra. The dilepton modification ratio presents interesting behavior at the backward rapidities when compared with the already known forward ones, since it is related with the large x kinematical region that is being probed. The rapidity dependence of the nuclear modification ratio in the dilepton production is strongly dependent on the Bjorken x behavior of the nuclear structure function ratio R F 2 =F 2 A /F 2 p . The R pA transverse momentum dependence at backward rapidities is modified due to the large x nuclear effects: at RHIC energies, for instance, the ratio R pA is reduced as p T increases, presenting an opposite behavior when compared with the forward one. It implies that the dilepton production at backward rapidities should carry information of the nuclear effects at large Bjorken x, as well as that it is useful to investigate the p T dependence of the observables in this kinematical regime

  1. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.M.; Kearsley, J.H.; Lee, C.S.; Sarris, M.; De Murrell, D.

    2000-01-01

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  2. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  3. Fisheries regulation

    DEFF Research Database (Denmark)

    Jensen, Frank; Frost, Hans Staby; Abildtrup, Jens

    2017-01-01

    Economists normally claim that a stock externality arises within fisheries because each individual fisherman does not take the effect on stock size into account when making harvest decisions. Due to the stock externality, it is commonly argued that fisheries regulation is necessary, but regulatory...... decisions are complicated by a tremendous amount of uncertainty and asymmetric information. This paper provides an overview of selected parts of the literature on the regulation of fisheries under uncertainty and asymmetric information, and possible areas for future research are identified. Specifically...

  4. Rapid

    Directory of Open Access Journals (Sweden)

    Nahla M. Wassim

    2013-01-01

    Full Text Available Members of Aedes caspius mosquitoes are incriminated to be a potential reservoir of “Rift Valley Fever Virus” (RVF during interepizootic periods in Egypt. Ae. caspius contains two distinct forms which are morphologically indistinguishable but differ in physiology and behavior; Ae. caspius form (a requires a blood meal for each egg batch(anautogeny, is unable to mate in confined spaces(eurygamous. The second form (b lays egg batch without blood meal (autogenous and can mate in confined spaces (stenogamous. In this work, we collected the autogenous and anautogenous forms of Ae. caspius from two different breeding habitats in the Qalyubia Governorate. Analysis of the Drosophila ace-Orthologous acetylecholinesterase gene revealed that a single polymorphic region characterized each species. Based on this region, specific primers were used to amplify the entire section of intron II, sections of Exon 2 and Exon 3 of ace-2 gene for differentiating the complex species of mosquitoes. The amplicons of anautogenous form sized 441 pb and increase 116 bp than autogenous form of Ae. caspius. High rates of point mutations were addressed; deletion/insertion events are 120 bases. The transversion mutations were 44 bases and were relatively close to the transtion mutations 43 base. The genetic distance was 0.01 between the two forms.

  5. The Most Probable Limit of Detection (MPL) for rapid microbiological methods

    NARCIS (Netherlands)

    Verdonk, G.P.H.T.; Willemse, M.J.; Hoefs, S.G.G.; Cremers, G.; Heuvel, E.R. van den

    Classical microbiological methods have nowadays unacceptably long cycle times. Rapid methods, available on the market for decades, are already applied within the clinical and food industry, but the implementation in pharmaceutical industry is hampered by for instance stringent regulations on

  6. The most probable limit of detection (MPL) for rapid microbiological methods

    NARCIS (Netherlands)

    Verdonk, G.P.H.T.; Willemse, M.J.; Hoefs, S.G.G.; Cremers, G.; Heuvel, van den E.R.

    2010-01-01

    Classical microbiological methods have nowadays unacceptably long cycle times. Rapid methods, available on the market for decades, are already applied within the clinical and food industry, but the implementation in pharmaceutical industry is hampered by for instance stringent regulations on

  7. Rapid islanding detection using multi-level inverter for grid-interactive PV system

    International Nuclear Information System (INIS)

    Tsang, K.M.; Chan, W.L.

    2014-01-01

    Graphical abstract: - Highlights: • Novel reference signal is used to form an islanding detection scheme for PV system. • Supply fixed magnitude sinusoidal signal even if utility grid is disconnected. • Seamless transfer between grid-connected and stand-alone modes is possible. - Abstract: A novel reference signal generator is combined with a multi-level inverter to form a rapid islanding detection scheme for grid-interactive PV system. The reference signal generator can easily be synchronized with the utility grid signal and produced a fixed magnitude and very low total harmonic distortion (THD) sinusoidal signal which is in phase with the utility grid signal. Unlike conventional phase-locked loop (PLL) circuitry, the reference signal generator can also provide a fixed magnitude sinusoidal signal even if the utility grid is disconnected and automatically re-synchronous with the grid rapidly. Consequently, seamless transfer between grid-connected and stand-alone modes could easily be achieved if anti-islanding protection is not required. If a saturation element is applied to the raw reference signal followed by the synthesis of the truncated signal using a multi-level inverter, the distinct flat-top feature of the synthesized signal can quickly and easily be identified if the network is in islanding mode at the point of common coupling. Experimental results are included to demonstrate the effectiveness of the proposed detection scheme

  8. French regulations

    International Nuclear Information System (INIS)

    Ballereau, P.

    1998-01-01

    In this issue are given the new French regulations relative to radiation protection of temporary personnel, the licensing to release gaseous and liquid wastes and the licensing granted to thirty two laboratories using beta and gamma decay radioisotopes. (N.C.)

  9. Hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Brandt, A.

    1995-09-01

    The field of hard diffraction, which studies events with a rapidity gap and a hard scattering, has expanded dramatically recently. A review of new results from CDF, D OE, H1 and ZEUS will be given. These results include diffractive jet production, deep-inelastic scattering in large rapidity gap events, rapidity gaps between high transverse energy jets, and a search for diffractive W-boson production. The combination of these results gives new insight into the exchanged object, believed to be the pomeron. The results axe consistent with factorization and with a hard pomeron that contains both quarks and gluons. There is also evidence for the exchange of a strongly interacting color singlet in high momentum transfer (36 2 ) events

  10. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-Zhong; Ai, Zhi-Ying [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Wang, Zhi-Wei [School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027 (China); Chen, Lin-Lin [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Guo, Ze-Kun, E-mail: gzknwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Zhang, Yong, E-mail: zylabnwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China)

    2015-09-25

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.

  11. On the rapid melt quenching

    International Nuclear Information System (INIS)

    Usatyuk, I.I.; Novokhatskij, I.A.; Kaverin, Yu.F.

    1994-01-01

    Specific features of instrumentation of traditionally employed method of melt spinning (rapid quenching), its disadvantages being discussed, were analyzed. The necessity of the method upgrading as applied to the problems of studying fine structure of molten metals and glasses was substantiated. The principle flowsheet of experimental facility for extremely rapid quenching of the melts of metals is described, specificity of its original functional units being considered. The sequence and character of all the principal stages of the method developed were discussed. 18 refs.; 3 figs

  12. Efficient protocol for rapid Aloe vera micropropagation.

    Science.gov (United States)

    Molsaghi, Mozhgan; Moieni, Ahmad; Kahrizi, Danial

    2014-06-01

    Aloe vera Linn. (Liliaceae) is a medicinal plant and has a number of curative properties. Vegetative propagation has not enough potential for supplying market demand. However, via in vitro propagation makes possible the mass production of Aloe plants. The current study was conducted to investigate growth regulators' effects on proliferation of A. vera. In this study, for comparison of plant growth regulators' effects on proliferation, the shoot tips and auxiliary buds of A. vera were cultured in the Murashige and Skoog (MS) medium. Rooted plantlets were transferred to garden soil, compost, and sand in the proportion of 1:1:1, respectively, after hardening. The maximum number of shoots was obtained on the medium supplemented with 1 mg/L IAA+4 mg/L BAP and 0.2 mg/L IAA+0.8 BAP mg/L. Rooting was also achieved in the same media composition proliferation of shoot. The acclimatized plants showed 100% of survival. The regenerated plants looked healthy, and they were morphologically similar to that of stock plants. These results suggest that in vitro culture may be used as a technique for rapid propagation of A. vera.

  13. Furnace for rapid thermal processing

    NARCIS (Netherlands)

    Roozeboom, F.; Duine, P.A.; Sluis, P. van der

    2001-01-01

    A Method (1) for Rapid Thermal Processing of a wafer (7), wherein the wafer (7) is heated by lamps (9), and the heat radiation is reflected by an optical switching device (15,17) which is in the reflecting state during the heating stage. During the cooling stage of the wafer (7), the heat is

  14. Rapid thermal processing of semiconductors

    CERN Document Server

    Borisenko, Victor E

    1997-01-01

    Rapid thermal processing has contributed to the development of single wafer cluster processing tools and other innovations in integrated circuit manufacturing environments Borisenko and Hesketh review theoretical and experimental progress in the field, discussing a wide range of materials, processes, and conditions They thoroughly cover the work of international investigators in the field

  15. Rapid general microdetermination of fluorine

    NARCIS (Netherlands)

    Leuven, H.C.E. van; Rotscheid, G.J.; Buis, W.J.

    1979-01-01

    A rapid micromethod for the determination of fluorine in a wide variety of materials has been developed. The method is based on the liberation of the fluorine (as HF) from the sample by means of pyrohydrolysis with steam at 1120?? C, The amount of fluoride in the condensate is subsequently measured

  16. Rapid Prototyping Enters Mainstream Manufacturing.

    Science.gov (United States)

    Winek, Gary

    1996-01-01

    Explains rapid prototyping, a process that uses computer-assisted design files to create a three-dimensional object automatically, speeding the industrial design process. Five commercially available systems and two emerging types--the 3-D printing process and repetitive masking and depositing--are described. (SK)

  17. Portable Diagnostics and Rapid Germination

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Zachary Spencer [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-12-01

    In the Bioenergy and Defense Department of Sandia National Laboratories, characterization of the BaDx (Bacillus anthracis diagnostic cartridge) was performed and rapid germination chemistry was investigated. BaDx was tested with complex sample matrixes inoculated with Bacillus anthracis, and the trials proved that BaDx will detect Bacillus anthracis in a variety of the medium, such as dirt, serum, blood, milk, and horse fluids. The dimensions of the device were altered to accommodate an E. coli or Listeria lateral flow immunoassay, and using a laser printer, BaDx devices were manufactured to identify E. coli and Listeria. Initial testing with E. coli versions of BaDx indicate that the device will be viable as a portable diagnostic cartridge. The device would be more effective with faster bacteria germination; hence studies were performed the use of rapid germination chemistry. Trials with calcium dipicolinic acid displayed increased cell germination, as shown by control studies using a microplate reader. Upon lyophilization the rapid germination chemistry failed to change growth patterns, indicating that the calcium dipicolinic acid was not solubilized under the conditions tested. Although incompatible with the portable diagnostic device, the experiments proved that the rapid germination chemistry was effective in increasing cell germination.

  18. Regulating Internalities

    OpenAIRE

    Sunstein, Cass Robert; Allcott, Hunt

    2015-01-01

    This paper offers a framework for regulating internalities. Using a simple economic model, we provide four principles for designing and evaluating behaviorally-motivated policy. We then outline rules for determining which contexts reliably reflect true preferences and discuss empirical strategies for measuring internalities. As a case study, we focus on energy efficiency policy, including Corporate Average Fuel Economy (CAFE) standards and appliance and lighting energy efficiency standards.

  19. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality

    NARCIS (Netherlands)

    van Tol, Marie-José; Veer, Ilya M.; van der Wee, Nic J. A.; Aleman, André; van Buchem, Mark A.; Rombouts, Serge A. R. B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether

  20. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder : Abnormal salience circuitry and relations to positive emotionality

    NARCIS (Netherlands)

    van Tol, Marie-Jose; Veer, Ilya M.; van der Wee, Nic J. A.; Aleman, Andre; van Buchem, Mark A.; Rombouts, Serge A. R. B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether

  1. Rapid-scan EPR imaging.

    Science.gov (United States)

    Eaton, Sandra S; Shi, Yilin; Woodcock, Lukas; Buchanan, Laura A; McPeak, Joseph; Quine, Richard W; Rinard, George A; Epel, Boris; Halpern, Howard J; Eaton, Gareth R

    2017-07-01

    In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250MHz. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Rapid shift in substrate utilization driven by hypothalamic Agrp neurons

    OpenAIRE

    Cavalcanti-De-Albuquerque, Joao; Dietrich, Marcelo; Bober, Jeremy; Zimmer, Marcelo

    2016-01-01

    Agrp neurons drive feeding. To what extend these neurons participate in the regulation of other homeostatic processes is not well understood. We investigated the role of Agrp neurons in substrate utilization in mice. Activation of Agrp neurons was sufficient to rapidly increase RER and carbohydrate utilization, while decreasing fat utilization. These metabolic changes were linearly correlated with carbohydrates ingested, but not protein or fat ingestion. However, even in the absence of ingest...

  3. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...... that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...

  4. Easy to remember, difficult to forget: The development of fear regulation

    Directory of Open Access Journals (Sweden)

    D.C. Johnson

    2015-02-01

    Full Text Available Fear extinction learning is a highly adaptive process that involves the integrity of frontolimbic circuitry. Its disruption has been associated with emotional dysregulation in stress and anxiety disorders. In this article we consider how age, genetics and experiences shape our capacity to regulate fear in cross-species studies. Evidence for adolescent-specific diminished fear extinction learning is presented in the context of immature frontolimbic circuitry. We also present evidence for less neural plasticity in fear regulation as a function of early-life stress and by genotype, focusing on the common brain derived neurotrophin factor (BDNF Val66Met polymorphism. Finally, we discuss this work in the context of exposure-based behavioral therapies for the treatment of anxiety and stress disorders that are based on principles of fear extinction. We conclude by speculating on how such therapies may be optimized for the individual based on the patient's age, genetic profile and personal history to move from standard treatment of care to personalized and precision medicine.

  5. Low stored energy 100 kV regulator for ion sources at LANSCE

    International Nuclear Information System (INIS)

    Jacobson, E.G.; Haffner, R.L.; Ingalls, W.B.; Meyer, B.J.; Stelzer, J.E.

    1998-01-01

    To minimize accelerating column damage caused by uncontrolled energy release during arc-downs, it is desirable to minimize the available stored electrical energy. For the Los Alamos Neutron Science Center (LANSCE) H - ion sources, the stored energy includes, in addition to the charge in the power supply output capacitance, the charge on the electronics racks. They are supported and insulated from ground by PVC pipe and have a capacitance to ground of approximately 900 pf. In 1988 (LANSCE) personnel designed a high-voltage current source using a low-stored-energy power supply and planar triode with the goal of eliminating uncontrolled release of charge stored in the power supply. Construction and testing were performed intermittently as resources permitted until 1993. When work on the Short Pulse Spallation Source (SPSS) started on the LANSCE Ion Source Test Stand (ISTS) it was recognized that a higher current power supply would be needed and work resumed on the regulator circuitry. A 120 kV power supply having low output capacitance, and a planar triode have been used to supply 40 mA, 120 Hz, 12% duty-factor current for the ISTS beam. The triode's cathode current is controlled by circuitry operating both at power-supply voltage level and at ground level via a fiber optic link. Voltage droop is approximately 600 V during the 1 ms beam pulse. The authors present the status of the regulator and its special challenges

  6. Rapid and sustained cost management

    International Nuclear Information System (INIS)

    Hanson, D.

    2009-01-01

    Accenture helps clients develop comprehensive, process-driven strategies for rapid and sustained cost management that leverage deep insights and analytics. This approach enables companies to gain operating cost advantages by rationalizing, simplifying and automating current operating capabilities. It drives structural cost advantages by optimizing business mix, capital structure, organizational structure and geographic presence. This paper discussed how successful companies achieve high performance during times of economic turmoil. It also discussed the value of the winner's strategy in terms of rapid and sustained cost management (RSCM). It discussed how Accenture operates and its leveraged capabilities, improved efficiency, margins and cash flow while maintaining customer service levels. Building structural advantage and the Accenture difference were also discussed. It was concluded that RSCM is one vital way that Accenture can help companies achieve success. 4 figs

  7. Rapidly Progressive Quadriplegia and Encephalopathy.

    Science.gov (United States)

    Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

    2016-11-01

    A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

  8. Rapid mask prototyping for microfluidics.

    Science.gov (United States)

    Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

    2016-03-01

    With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

  9. Rapidity correlations test stochastic hydrodynamics

    International Nuclear Information System (INIS)

    Zin, C; Gavin, S; Moschelli, G

    2017-01-01

    We show that measurements of the rapidity dependence of transverse momentum correlations can be used to determine the characteristic time τ π that dictates the rate of isotropization of the stress energy tensor, as well as the shear viscosity ν = η/sT . We formulate methods for computing these correlations using second order dissipative hydrodynamics with noise. Current data are consistent with τ π /ν ∼ 10 but targeted measurements can improve this precision. (paper)

  10. Rapid duodenal and jejunal intubation

    International Nuclear Information System (INIS)

    Nolan, D.J.

    1979-01-01

    A size 12 French radiopaque catheter, 135 cm long, suitable for rapid duodenal and jejunal intubation, is described. Its size and flexibility enable it to be passed with ease through the nose, stomach and duodenum. A guide wire is used to act as a stiffener as the catheter is passed through the stomach. The catheter is suitable for infusing barium directly into the small intestine and for performing hypotonic duodenography. The technique for duodenal and jejunal intubation is discussed. (author)

  11. Rapid synthesis of beta zeolites

    Science.gov (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  12. Rapid reconnection of flux lines

    International Nuclear Information System (INIS)

    Samain, A.

    1982-01-01

    The rapid reconnection of flux lines in an incompressible fluid through a singular layer of the current density is discussed. It is shown that the liberated magnetic energy must partially appear in the form of plasma kinetic energy. A laminar structure of the flow is possible, but Alfven velocity must be achieved in eddies of growing size at the ends of the layer. The gross structure of the flow and the magnetic configuration may be obtained from variational principles. (author)

  13. Single wafer rapid thermal multiprocessing

    International Nuclear Information System (INIS)

    Saraswat, K.C.; Moslehi, M.M.; Grossman, D.D.; Wood, S.; Wright, P.; Booth, L.

    1989-01-01

    Future success in microelectronics will demand rapid innovation, rapid product introduction and ability to react to a change in technological and business climate quickly. These technological advances in integrated electronics will require development of flexible manufacturing technology for VLSI systems. However, the current approach of establishing factories for mass manufacturing of chips at a cost of more than 200 million dollars is detrimental to flexible manufacturing. The authors propose concepts of a micro factory which may be characterized by more economical small scale production, higher flexibility to accommodate many products on several processes, and faster turnaround and learning. In-situ multiprocessing equipment where several process steps can be done in sequence may be a key ingredient in this approach. For this environment to be flexible, the equipment must have ability to change processing environment, requiring extensive in-situ measurements and real time control. This paper describes the development of a novel single wafer rapid thermal multiprocessing (RTM) reactor for next generation flexible VLSI manufacturing. This reactor will combine lamp heating, remote microwave plasma and photo processing in a single cold-wall chamber, with applications for multilayer in-situ growth and deposition of dielectrics, semiconductors and metals

  14. Rapid Sampling from Sealed Containers

    International Nuclear Information System (INIS)

    Johnston, R.G.; Garcia, A.R.E.; Martinez, R.K.; Baca, E.T.

    1999-01-01

    The authors have developed several different types of tools for sampling from sealed containers. These tools allow the user to rapidly drill into a closed container, extract a sample of its contents (gas, liquid, or free-flowing powder), and permanently reseal the point of entry. This is accomplished without exposing the user or the environment to the container contents, even while drilling. The entire process is completed in less than 15 seconds for a 55 gallon drum. Almost any kind of container can be sampled (regardless of the materials) with wall thicknesses up to 1.3 cm and internal pressures up to 8 atm. Samples can be taken from the top, sides, or bottom of a container. The sampling tools are inexpensive, small, and easy to use. They work with any battery-powered hand drill. This allows considerable safety, speed, flexibility, and maneuverability. The tools also permit the user to rapidly attach plumbing, a pressure relief valve, alarms, or other instrumentation to a container. Possible applications include drum venting, liquid transfer, container flushing, waste characterization, monitoring, sampling for archival or quality control purposes, emergency sampling by rapid response teams, counter-terrorism, non-proliferation and treaty verification, and use by law enforcement personnel during drug or environmental raids

  15. Differential Patterns of Abnormal Activity and Connectivity in the Amygdala-Prefrontal Circuitry in Bipolar-I and Bipolar-NOS Youth

    Science.gov (United States)

    Ladouceur, Cecile D.; Farchione, Tiffany; Diwadkar, Vaibhav; Pruitt, Patrick; Radwan, Jacqueline; Axelson, David A.; Birmaher, Boris; Phillips, Mary L.

    2011-01-01

    Objective: The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). Method:…

  16. Childhood trauma exposure disrupts the automatic regulation of emotional processing.

    Science.gov (United States)

    Marusak, Hilary A; Martin, Kayla R; Etkin, Amit; Thomason, Moriah E

    2015-03-13

    Early-life trauma is one of the strongest risk factors for later emotional psychopathology. Although research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown whether neural and behavioral changes that may precipitate illness are evident during formative, developmental years. This study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. A total of 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala-pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity that was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity that is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early-life trauma.

  17. Rapid Adaptation in Digital Transformation

    DEFF Research Database (Denmark)

    Hansen, Anne Mette; Kræmmergaard, Pernille; Mathiassen, Lars

    2011-01-01

    landscape. In this article, we share insights gained from two public sector organizations in which IS and business leaders used the Participatory Process Model (PPM) designed by the authors to share their assumptions about IS leadership, challenge existing IT strategies and collaboration patterns and adapt...... the organization’s digitization approach. We demonstrate in detail how the leaders within these two organizations were engaged and offer recommendations for how other organizations can use the PPM to rapidly adapt their approaches to digital transformation through more effective IS leadership roles....

  18. Rapid thermal processing by stamping

    Science.gov (United States)

    Stradins, Pauls; Wang, Qi

    2013-03-05

    A rapid thermal processing device and methods are provided for thermal processing of samples such as semiconductor wafers. The device has components including a stamp (35) having a stamping surface and a heater or cooler (40) to bring it to a selected processing temperature, a sample holder (20) for holding a sample (10) in position for intimate contact with the stamping surface; and positioning components (25) for moving the stamping surface and the stamp (35) in and away from intimate, substantially non-pressured contact. Methods for using and making such devices are also provided. These devices and methods allow inexpensive, efficient, easily controllable thermal processing.

  19. Rapidly Adaptable Instrumentation Tester (RAIT)

    International Nuclear Information System (INIS)

    Vargo, Timothy D.

    1999-01-01

    Emerging technologies in the field of ''Test ampersand Measurement'' have recently enabled the development of the Rapidly Adaptable Instrumentation Tester (RAIT). Based on software developed with LabVIEW, the RAIT design enables quick reconfiguration to test and calibrate a wide variety of telemetry systems. The consequences of inadequate testing could be devastating if a telemetry system were to fail during an expensive flight mission. Supporting both open-bench testing as well as automated test sequences, the RAIT has significantly lowered total time required to test and calibrate a system. This has resulted in an overall lower per unit testing cost than has been achievable in the past

  20. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Melcher, Cynthia P.

    2015-08-28

    The Wyoming Basin Rapid Ecoregional Assessment was conducted in partnership with the Bureau of Land Management (BLM). The overall goals of the BLM Rapid Ecoregional Assessments (REAs) are to identify important ecosystems and wildlife habitats at broad spatial scales; identify where these resources are at risk from Change Agents, including development, wildfire, invasive species, disease and climate change; quantify cumulative effects of anthropogenic stressors; and assess current levels of risk to ecological resources across a range of spatial scales and jurisdictional boundaries by assessing all lands within an ecoregion. There are several components of the REAs. Management Questions, developed by the BLM and stakeholders for the ecoregion, identify the regionally significant information needed for addressing land-management responsibilities. Conservation Elements represent regionally significant species and ecological communities that are of management concern. Change Agents that currently affect or are likely to affect the condition of species and communities in the future are identified and assessed. REAs also identify areas that have high conservation potential that are referred to as “large intact areas.” At the ecoregion level, the ecological value of large intact areas is based on the assumption that because these areas have not been greatly altered by human activities (such as development), they are more likely to contain a variety of plant and animal communities and to be resilient and resistant to changes resulting from natural disturbances such as fire, insect outbreaks, and disease.

  1. Direct, rapid RNA sequence analysis

    International Nuclear Information System (INIS)

    Peattie, D.A.

    1987-01-01

    The original methods of RNA sequence analysis were based on enzymatic production and chromatographic separation of overlapping oligonucleotide fragments from within an RNA molecule followed by identification of the mononucleotides comprising the oligomer. Over the past decade the field of nucleic acid sequencing has changed dramatically, however, and RNA molecules now can be sequenced in a variety of more streamlined fashions. Most of the more recent advances in RNA sequencing have involved one-dimensional electrophoretic separation of 32 P-end-labeled oligoribonucleotides on polyacrylamide gels. In this chapter the author discusses two of these methods for determining the nucleotide sequences of RNA molecules rapidly: the chemical method and the enzymatic method. Both methods are direct and degradative, i.e., they rely on fragmatic and chemical approaches should be utilized. The single-strand-specific ribonucleases (A, T 1 , T 2 , and S 1 ) provide an efficient means to locate double-helical regions rapidly, and the chemical reactions provide a means to determine the RNA sequence within these regions. In addition, the chemical reactions allow one to assign interactions to specific atoms and to distinguish secondary interactions from tertiary ones. If the RNA molecule is small enough to be sequenced directly by the enzymatic or chemical method, the probing reactions can be done easily at the same time as sequencing reactions

  2. Rapid learning: a breakthrough agenda.

    Science.gov (United States)

    Etheredge, Lynn M

    2014-07-01

    A "rapid-learning health system" was proposed in a 2007 thematic issue of Health Affairs. The system was envisioned as one that uses evidence-based medicine to quickly determine the best possible treatments for patients. It does so by drawing on electronic health records and the power of big data to access large volumes of information from a variety of sources at high speed. The foundation for a rapid-learning health system was laid during 2007-13 by workshops, policy papers, large public investments in databases and research programs, and developing learning systems. Challenges now include implementing a new clinical research system with several hundred million patients, modernizing clinical trials and registries, devising and funding research on national priorities, and analyzing genetic and other factors that influence diseases and responses to treatment. Next steps also should aim to improve comparative effectiveness research; build on investments in health information technology to standardize handling of genetic information and support information exchange through apps and software modules; and develop new tools, data, and information for clinical decision support. Further advances will require commitment, leadership, and public-private and global collaboration. Project HOPE—The People-to-People Health Foundation, Inc.

  3. Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

    Science.gov (United States)

    Bracha, H Stefan

    2006-07-01

    The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing

  4. Alzheimer’s disease Aβ assemblies mediating rapid disruption of synaptic plasticity and memory

    Directory of Open Access Journals (Sweden)

    Klyubin Igor

    2012-07-01

    Full Text Available Abstract Alzheimer’s disease (AD is characterized by episodic memory impairment that often precedes clinical diagnosis by many years. Probing the mechanisms of such impairment may provide much needed means of diagnosis and therapeutic intervention at an early, pre-dementia, stage. Prior to the onset of significant neurodegeneration, the structural and functional integrity of synapses in mnemonic circuitry is severely compromised in the presence of amyloidosis. This review examines recent evidence evaluating the role of amyloid-ß protein (Aβ in causing rapid disruption of synaptic plasticity and memory impairment. We evaluate the relative importance of different sizes and conformations of Aβ, including monomer, oligomer, protofibril and fibril. We pay particular attention to recent controversies over the relevance to the pathophysiology of AD of different water soluble Aβ aggregates and the importance of cellular prion protein in mediating their effects. Current data are consistent with the view that both low-n oligomers and larger soluble assemblies present in AD brain, some of them via a direct interaction with cellular prion protein, cause synaptic memory failure. At the two extremes of aggregation, monomers and fibrils appear to act in vivo both as sources and sinks of certain metastable conformations of soluble aggregates that powerfully disrupt synaptic plasticity. The same principle appears to apply to other synaptotoxic amyloidogenic proteins including tau, α-synuclein and prion protein.

  5. Method for rapid particle size analysis by hydrosizing and nuclear sensing

    International Nuclear Information System (INIS)

    Daellenbach, C.B.; Mahan, W.M.

    1977-01-01

    A method and apparatus to practice the method for rapidly determining the size and mass distribution of a sample of randomly sized particles of a known total mass are described. A series of substantially identical hydrocyclones are connected by conduits to each other and to a temperature controlled water feed. By restricting the cross-sectional areas of these conduits to progressively smaller values, the slurry containing the sample particles is caused to increase its velocity as it moves from hydrocyclone to hydrocyclone. As described by the Stokesian theory which relates particle diameter and settling velocity, the largest sized particles are suspended in the closed apex of the first hydrocyclone with smaller sized particles, in given size ranges, being suspended in the next succeeding hydrocyclone's apexes. In this manner, the particles are separated into discrete fractional sizes with a residual slurry of the very smallest particles being discharged. Before the discrete fractions of particles are suspended in their hydrocyclone apexes, a combined photon source, like a gamma ray source, and detector are calibrated with the water temperature kept constant. When the suspension of particles takes place, an attenuation of the radiation from the source is observed at the detector. This attenuation can be related to the mass or weight of the discrete fractions of suspended particles. Electronic circuitry is used to indicate what this fractional mass or weight is as it relates to the total weight of the sample. 6 claims, 4 figs

  6. Regulation of bacterial virulence by Csr (Rsm) systems.

    Science.gov (United States)

    Vakulskas, Christopher A; Potts, Anastasia H; Babitzke, Paul; Ahmer, Brian M M; Romeo, Tony

    2015-06-01

    Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5' untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. THERMAL REGULATION OF THE BRAIN -AN ANATOMICAL AND PHYSIOLOGICAL REVIEW FOR CLINICAL NEUROSCIENTISTS

    Directory of Open Access Journals (Sweden)

    Huan (John eWang

    2016-01-01

    Full Text Available Humans, like all mammals and birds, maintain a nearly constant core body temperature (36 -37.5°C over a wide range of environmental conditions and are thus referred to as endotherms. The evolution of the brain and its supporting structures in mammals and birds coincided with this development of endothermy. Despite the recognition that a more evolved and complicated brain with all of its temperature-dependent cerebral circuitry and neuronal processes would require more sophisticated thermal control mechanisms, the current understanding of brain temperature regulation remains limited. To optimize the development and maintenance of the brain in health and to accelerate its healing and restoration in illness, focused and committed efforts are much needed to advance the fundamental understanding of brain temperature. In order to effectively study and examine brain temperature regulation, it is critical to first understand the relevant anatomical and physiological properties in the head-neck regions.

  8. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin......Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...

  9. Rapid chemical analysis of allanite

    International Nuclear Information System (INIS)

    Nishiyama, Goro; Hayashi, Hiroshi

    1981-01-01

    Rapid chemical analysis of allanite was studied by atomic absorption spectrophotometry. Powdered sample was fused with mixture of sodium carbonate anhydrous and borax (4 : 1 weight) in platinum crucible and sample solution was prepared. SiO 2 , Fe 2 O 3 , Al 2 O 3 , MnO and rare earth metals were determined by atomic absorption spectrophotometry, CaO, MgO and Ce 2 O 3 by titration, ThO 2 by colorimetry, and La 2 O 3 by flame photometry respectively. For sample solution treated with hydrofluoric acid and sulfuric acid. Na 2 O and K 2 O were determined by atomic absorption spectrophotometry, TiO 2 and P 2 O 5 by colorimetry. Chemical analyses for four samples were carried out and gave consistent results. (author)

  10. Rapid world modelling for robotics

    International Nuclear Information System (INIS)

    Littile, C.Q.; Wilson, C.W.

    1996-01-01

    The ability to use an interactive world model, whether it is for robotics simulation or most other virtual graphical environments, relies on the users ability to create an accurate world model. Typically this is a tedious process, requiring many hours to create 3-D CAD models of the surfaces within a workspace. The goal of this ongoing project is to develop usable methods to rapidly build world models of real world workspaces. This brings structure to an unstructured environment and allows graphical based robotics control to be accomplished in a reasonable time frame when traditional CAD modelling is not enough. To accomplish this, 3D range sensors are deployed to capture surface data within the workspace. This data is then transformed into surface maps, or models. A 3D world model of the workspace is built quickly and accurately, without ever having to put people in the environment

  11. On rapid rotation in stellarators

    International Nuclear Information System (INIS)

    Helander, Per

    2008-01-01

    The conditions under which rapid plasma rotation may occur in a three-dimensional magnetic field, such as that of a stellarator, are investigated. Rotation velocities comparable to the ion thermal speed are found to be attainable only in magnetic fields which are approximately isometric. In an isometric magnetic field the dependence of the magnetic field strength B on the arc length l along the field is the same for all field lines on each flux surface ψ. Only in fields where the departure from exact isometry, B=B(ψ,l), is of the order of the ion gyroradius divided by the macroscopic length scale are rotation speeds comparable to the ion thermal speed possible. Moreover, it is shown that the rotation must be in the direction of the vector ∇ψx∇B. (author)

  12. Microstructure of rapidly solidified materials

    Science.gov (United States)

    Jones, H.

    1984-07-01

    The basic features of rapidly solidified microstructures are described and differences arising from alternative processing strategies are discussed. The possibility of achieving substantial undercooling prior to solidification in processes such as quench atomization and chill block melt spinning can give rise to striking microstructural transitions even when external heat extraction is nominally Newtonian. The increased opportunity in laser and electron beam surface melting for epitaxial growth on the parent solid at an accelerating rate, however, does not exclude the formation of nonequilibrium phases since the required undercooling can be locally attained at the solidification front which is itself advancing at a sufficiently high velocity. The effects of fluid flow indicated particularly in melt spinning and surface melting are additional to the transformational and heat flow considerations that form the present basis for interpretation of such microstructural effects.

  13. Rapid iconic erasure without masking.

    Science.gov (United States)

    Tijus, Charles Albert; Reeves, Adam

    2004-01-01

    We report on the erasure of the iconic memory of an array of 12 black letters flashed on a continuously- present white field. Erasure is accomplished by replacing the 16 ms letter array (frame 1) with a blank white frame for 16 ms (frame 2). The letter array returns in frame 3, with from one to six letters missing. Report of the missing letters is accurate without the blank white frame but is impoverished with it, as if interposing the blank erases the icon. Erasure occurs without any obvious luminance masking, 'mud splashes', pattern masking (backward, forward, or metacontrast), lateral masking, or masking by object substitution. Erasure is greatly decreased if the blank is presented one frame earlier or later. We speculate that erasure is due to a rapid reset of the icon produced by an informational mis-match.

  14. Rapid onset aggressive vertebral haemangioma.

    Science.gov (United States)

    Cheung, Nicholas K; Doorenbosch, Xenia; Christie, John G

    2011-03-01

    Vertebral haemangiomas are generally benign asymptomatic vascular tumours seen commonly in the adult population. Presentations in paediatric populations are extremely rare, which can result in rapid onset of neurological symptoms. We present a highly unusual case of an aggressive paediatric vertebral haemangioma causing significant cord compression. A 13-year-old boy presented with only 2 weeks duration of progressive gait disturbance, truncal ataxia and loss of bladder control. Magnetic resonance imaging (MRI) of the spine revealed a large vascular epidural mass extending between T6 and T8 vertebral bodies. Associated displacement and compression of the spinal cord was present. A highly vascular bony lesion was found during surgery. Histopathology identified this tumour to be a vertebral haemangioma. We present an extremely unusual acute presentation of a paediatric vertebral haemangioma. This study highlights the need for early diagnosis, MRI for investigation and urgent surgical management. © Springer-Verlag 2011

  15. Customer-experienced rapid prototyping

    Science.gov (United States)

    Zhang, Lijuan; Zhang, Fu; Li, Anbo

    2008-12-01

    In order to describe accurately and comprehend quickly the perfect GIS requirements, this article will integrate the ideas of QFD (Quality Function Deployment) and UML (Unified Modeling Language), and analyze the deficiency of prototype development model, and will propose the idea of the Customer-Experienced Rapid Prototyping (CE-RP) and describe in detail the process and framework of the CE-RP, from the angle of the characteristics of Modern-GIS. The CE-RP is mainly composed of Customer Tool-Sets (CTS), Developer Tool-Sets (DTS) and Barrier-Free Semantic Interpreter (BF-SI) and performed by two roles of customer and developer. The main purpose of the CE-RP is to produce the unified and authorized requirements data models between customer and software developer.

  16. Chandra Data Reveal Rapidly Whirling Black Holes

    Science.gov (United States)

    2008-01-01

    A new study using results from NASA's Chandra X-ray Observatory provides one of the best pieces of evidence yet that many supermassive black holes are spinning extremely rapidly. The whirling of these giant black holes drives powerful jets that pump huge amounts of energy into their environment and affects galaxy growth. A team of scientists compared leading theories of jets produced by rotating supermassive black holes with Chandra data. A sampling of nine giant galaxies that exhibit large disturbances in their gaseous atmospheres showed that the central black holes in these galaxies must be spinning at near their maximum rates. People Who Read This Also Read... NASA’s Swift Satellite Catches First Supernova in The Act of Exploding Black Holes Have Simple Feeding Habits Jet Power and Black Hole Assortment Revealed in New Chandra Image Erratic Black Hole Regulates Itself "We think these monster black holes are spinning close to the limit set by Einstein's theory of relativity, which means that they can drag material around them at close to the speed of light," said Rodrigo Nemmen, a visiting graduate student at Penn State University, and lead author of a paper on the new results presented at American Astronomical Society in Austin, Texas. The research reinforces other, less direct methods previously used which have indicated that some stellar and supermassive black holes are spinning rapidly. According to Einstein's theory, a rapidly spinning black hole makes space itself rotate. This effect, coupled with gas spiraling toward the black hole, can produce a rotating, tightly wound vertical tower of magnetic field that flings a large fraction of the inflowing gas away from the vicinity of the black hole in an energetic, high-speed jet. Computer simulations by other authors have suggested that black holes may acquire their rapid spins when galaxies merge, and through the accretion of gas from their surroundings. "Extremely fast spin might be very common for large

  17. Rapid Prototyping in Instructional Design: Creating Competencies

    Science.gov (United States)

    Fulton, Carolyn D.

    2010-01-01

    Instructional designers working in rapid prototyping environments currently do not have a list of competencies that help to identify the knowledge, skills, and attitudes (KSAs) required in these workplaces. This qualitative case study used multiple cases in an attempt to identify rapid prototyping competencies required in a rapid prototyping…

  18. Early Forming a Hummingbird-like Hovering Neural Network Circuitry Pattern with Reentrant Spatiotemporal Energy-Sensory Orientation Privileged to Avoid “Epilepsy” Based on a Biomimetic Acetylcholinesterase Memcapacitor Prosthesis

    Directory of Open Access Journals (Sweden)

    Ellen T. Chen

    2015-08-01

    Full Text Available The hummingbird’s significant asymmetry hovering flight with energy conservation pattern is remarkable among all vertebrates. However, little is known to human’s neuronal network circuitry current flow pattern for whether or not has this privilege during slow wave sleeping (SWS. What is the advantage in order to avoid diseases if we have this network pattern ? A memory device was developed with nanostructured biomimetic acetylcholinesterase (ACHE gorge membrane on gold chips as memcapacitor 1, served as a normal brain network prosthesis, compared with a mutated ACHE prosthesis as device 2, for evaluation of neuronal network circuitry integrity in the presence of Amyloid- beta (Ab under the conditions of free from tracers and antibodies in spiked NIST SRM 965A human serum. Three categories of Reentrant Energy-Sensory images are presented based on infused brain pulse energies in a matrix of “Sensory Biomarkers” having frequencies over 0.25-333 Hz at free and fixed Ab levels, respectively. Early non-symptomatic epilepsy was indentified and predicted by device 2 due to Pathological High Frequency Oscillation (pHFO and large areas of 38 µM Ab re-depositions. Device 1 sensitively “feels” Ab damage because of its Frequency Oscillation (HFO enhanced the hummingbird- like hovering pattern with higher reentrant energy sensitivity of 0.12 pj/bit/s/µm3 without Ab compared with Ab, 13 aj/bit/s/µm3/nM over 3.8-471 nM range over 0.003-4s. Device 1 reliably detected early CR dysfunction privileged to avoid epilepsy.

  19. Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems.

    Science.gov (United States)

    Romeo, Tony; Vakulskas, Christopher A; Babitzke, Paul

    2013-02-01

    Originally described as a repressor of gene expression in the stationary phase of growth, CsrA (RsmA) regulates primary and secondary metabolic pathways, biofilm formation, motility, virulence circuitry of pathogens, quorum sensing and stress response systems by binding to conserved sequences in its target mRNAs and altering their translation and/or turnover. While the binding of CsrA to RNA is understood at an atomic level, new mechanisms of gene activation and repression by this protein are still emerging. In the γ-proteobacteria, small non-coding RNAs (sRNAs) use molecular mimicry to sequester multiple CsrA dimers away from mRNA. In contrast, the FliW protein of Bacillus subtilis inhibits CsrA activity by binding to this protein, thereby establishing a checkpoint in flagellum morphogenesis. Turnover of CsrB and CsrC sRNAs in Escherichia coli requires a specificity protein of the GGDEF-EAL domain superfamily, CsrD, in addition to the housekeeping nucleases RNase E and PNPase. The Csr system of E. coli contains extensive autoregulatory circuitry, which governs the expression and activity of CsrA. Interaction of the Csr system with transcriptional regulatory networks results in a variety of complex response patterns. This minireview will highlight basic principles and new insights into the workings of these complex eubacterial regulatory systems. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  20. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor.

    Science.gov (United States)

    Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Seunghee; Lee, Soo-Kyung; Lee, Jae W

    2013-10-01

    Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance.

  1. Synaptic inputs compete during rapid formation of the calyx of Held: a new model system for neural development.

    Science.gov (United States)

    Holcomb, Paul S; Hoffpauir, Brian K; Hoyson, Mitchell C; Jackson, Dakota R; Deerinck, Thomas J; Marrs, Glenn S; Dehoff, Marlin; Wu, Jonathan; Ellisman, Mark H; Spirou, George A

    2013-08-07

    Hallmark features of neural circuit development include early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems, including the neuromuscular junction and climbing fiber innervation of Purkinje cells, are models to study neural development in part because they establish a recognizable endpoint of monoinnervation of their targets and because the presynaptic terminals are large and easily monitored. We demonstrate here that calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits all of these characteristics. To investigate CH development, we made the first application of serial block-face scanning electron microscopy to neural development with fine temporal resolution and thereby accomplished the first time series for 3D ultrastructural analysis of neural circuit formation. This approach revealed a growth spurt of added apposed surface area (ASA)>200 μm2/d centered on a single age at postnatal day 3 in mice and an initial rapid phase of growth and competition that resolved to monoinnervation in two-thirds of cells within 3 d. This rapid growth occurred in parallel with an increase in action potential threshold, which may mediate selection of the strongest input as the winning competitor. ASAs of competing inputs were segregated on the cell body surface. These data suggest mechanisms to select "winning" inputs by regional reinforcement of postsynaptic membrane to mediate size and strength of competing synaptic inputs.

  2. Rapid charging of nickel-cadmium accumulators

    Energy Technology Data Exchange (ETDEWEB)

    Bruck, F

    1972-01-01

    Four types of charging of gas-tight Ni-Cd accumulators (a) normal; (b) accelerated; (c) rapid; and (d) ultra-rapid are described. For rapid charging, a built-in temperature sensor cuts off charging current at a prescribed point. In ultra-rapid charging, 50% charge can be attained in 3.5 min. and 25% charge within 50 sec. In the second phase of ultra-rapid charging, a surplus of oxygen is released at the positive electrode and a safety valve is provided for pressure reduction. Characteristic curves are given for various rates of charging and some data on discharge rates is also given.

  3. Rapid typing of Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Heidie M Hornstra

    Full Text Available Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels among multispacer sequence typing (MST loci and designed 14 SNP-based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies.

  4. Rapid contextual conditioning in autoshaping.

    Science.gov (United States)

    Balsam, P D; Schwartz, A L

    1981-10-01

    Two experiments are reported which investigate the speed of contextual conditioning in autoshaping. In both experiments, a procedure was employed in which ring doves were magazine trained in one context prior to the manipulation of background values in a second context. In Experiment 1, subjects were exposed to 4, 8, 64, 128, or 256 US-only presentations prior to autoshaping. Acquisition speed and maintained response measures were monotonically related to the number of pretraining trials. Subjects in Group 4 acquired the key-peck response fastest, and retardation was maximal within 64 pretraining trials. In Experiment 2, subjects given 20 pretraining trials were significantly more retarded than subjects given 2 pretraining trials, but only when pretraining and testing were conducted in the same context. Overall, the results of these experiments show that in autoshaping, contextual conditioning is very rapid; this demonstrates the plausibility of theoretical accounts of Pavlovian conditioning which assert that the development of the conditioned response depends on the associative values of both the CS and background stimuli.

  5. Rapid Gradient-Echo Imaging

    Science.gov (United States)

    Hargreaves, Brian

    2012-01-01

    Gradient echo sequences are widely used in magnetic resonance imaging (MRI) for numerous applications ranging from angiography to perfusion to functional MRI. Compared with spin-echo techniques, the very short repetition times of gradient-echo methods enable very rapid 2D and 3D imaging, but also lead to complicated “steady states.” Signal and contrast behavior can be described graphically and mathematically, and depends strongly on the type of spoiling: fully balanced (no spoiling), gradient spoiling, or RF-spoiling. These spoiling options trade off between high signal and pure T1 contrast while the flip angle also affects image contrast in all cases, both of which can be demonstrated theoretically and in image examples. As with spin-echo sequences, magnetization preparation can be added to gradient-echo sequences to alter image contrast. Gradient echo sequences are widely used for numerous applications such as 3D perfusion imaging, functional MRI, cardiac imaging and MR angiography. PMID:23097185

  6. Rapidly developing market regions : Brazil

    International Nuclear Information System (INIS)

    Britto, A.

    1997-01-01

    Brazil and the State of Rio Grande do Sul are experiencing a period of rapid industrial development. Global investment has been forecast to reach $240 billion over the next five to seven years. This level of development is likely to result in a sharp increase in the consumption of plastic products made from olefins and from aromatic products. Accordingly, Copesul, the centre of raw materials for the State complex, is expected to increase its production of ethane from 685 tonnes to 1.13 million tonnes after 1999. The government has established a program of incentives to stimulate investment in third generation industries. Also, the State petrochemical industry has been rendered more competitive as a result of the purchase of the latest generation equipment. The principal challenges that exist for the petrochemical industry in Brazil and for that matter, around the world, are to reduce production costs and to preserve the natural environment. Another challenge, also world-wide, is to address the issue of plastic residues and to eliminate such residues through plastic recycling programs

  7. Rapidly Progressive Corticobasal Degeneration Syndrome

    Directory of Open Access Journals (Sweden)

    Ana Herrero Valverde

    2011-08-01

    Full Text Available Introduction: Corticobasal syndrome (CBS has a heterogeneous clinical presentation with no specific pathologic substratum. Its accurate diagnosis is a challenge for neurologists; in order to establish CBS definitively, postmortem confirmation is required. Some clinical and radiological features can help to distinguish it from other neurodegenerative conditions, such as Creutzfeldt-Jakob disease (CJD. Clinical Case: A 74-year-old woman presented with language impairment, difficulty in walking and poor attentiveness that had begun 10 days before. Other symptoms, such as asymmetrical extra-pyramidal dysfunction, limb dystonia and ‘alien limb’ phenomena, were established over the next 2 months, with rapid progression. Death occurred 3 months after symptom onset. Laboratory results were normal. Initially, imaging only showed restricted diffusion with bilateral parieto-occipital gyri involvement on DWI-MRI, with unspecific EEG changes. An autopsy was performed. Brain neuropathology confirmed sporadic CJD (sCJD. Conclusions: CBS is a heterogeneous clinical syndrome whose differential diagnosis is extensive. CJD can occasionally present with clinical characteristics resembling CBS. MRI detection of abnormalities in some sequences (FLAIR, DWI, as previously reported, has high diagnostic utility for sCJD diagnosis – especially in early stages – when other tests can still appear normal. Abnormalities on DWI sequencing may not correlate with neuropathological findings, suggesting a functional basis to explain the changes found.

  8. Rapid purification of recombinant histones.

    Science.gov (United States)

    Klinker, Henrike; Haas, Caroline; Harrer, Nadine; Becker, Peter B; Mueller-Planitz, Felix

    2014-01-01

    The development of methods to assemble nucleosomes from recombinant histones decades ago has transformed chromatin research. Nevertheless, nucleosome reconstitution remains time consuming to this day, not least because the four individual histones must be purified first. Here, we present a streamlined purification protocol of recombinant histones from bacteria. We termed this method "rapid histone purification" (RHP) as it circumvents isolation of inclusion bodies and thereby cuts out the most time-consuming step of traditional purification protocols. Instead of inclusion body isolation, whole cell extracts are prepared under strongly denaturing conditions that directly solubilize inclusion bodies. By ion exchange chromatography, the histones are purified from the extracts. The protocol has been successfully applied to all four canonical Drosophila and human histones. RHP histones and histones that were purified from isolated inclusion bodies had similar purities. The different purification strategies also did not impact the quality of octamers reconstituted from these histones. We expect that the RHP protocol can be readily applied to the purification of canonical histones from other species as well as the numerous histone variants.

  9. Molecular Mechanisms of Appetite Regulation

    Directory of Open Access Journals (Sweden)

    Ji Hee Yu

    2012-12-01

    Full Text Available The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

  10. Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

    Science.gov (United States)

    Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

    2012-10-01

    The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

  11. Rapid stress-induced transcriptomic changes in the brain depend on beta-adrenergic signaling.

    Science.gov (United States)

    Roszkowski, Martin; Manuella, Francesca; von Ziegler, Lukas; Durán-Pacheco, Gonzalo; Moreau, Jean-Luc; Mansuy, Isabelle M; Bohacek, Johannes

    2016-08-01

    Acute exposure to stressful experiences can rapidly increase anxiety and cause neuropsychiatric disorders. The effects of stress result in part from the release of neurotransmitters and hormones, which regulate gene expression in different brain regions. The fast neuroendocrine response to stress is largely mediated by norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a slower and more sustained release of corticosterone. While corticosterone is an important regulator of gene expression, it is not clear which stress-signals contribute to the rapid regulation of gene expression observed immediately after stress exposure. Here, we demonstrate in mice that 45 min after an acute swim stress challenge, large changes in gene expression occur across the transcriptome in the hippocampus, a region sensitive to the effects of stress. We identify multiple candidate genes that are rapidly and transiently altered in both males and females. Using a pharmacological approach, we show that most of these rapidly induced genes are regulated by NE through β-adrenergic receptor signaling. We find that CRH and corticosterone can also contribute to rapid changes in gene expression, although these effects appear to be restricted to fewer genes. These results newly reveal a widespread impact of NE on the transcriptome and identify novel genes associated with stress and adrenergic signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The Influence of Emotion Regulation on Decision-making under Risk

    Science.gov (United States)

    Martin, Laura N.; Delgado, Mauricio R.

    2011-01-01

    Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison to trials where decisions were made in the absence of cognitive regulation. Additionally, blood-oxygen-level-dependent (BOLD) responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum), and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse). PMID:21254801

  13. The influence of emotion regulation on decision-making under risk.

    Science.gov (United States)

    Martin, Laura N; Delgado, Mauricio R

    2011-09-01

    Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison with trials where decisions were made in the absence of cognitive regulation. Additionally, BOLD responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum) and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse).

  14. A mass spectrometer for the rapid analysis of gaseous mixtures

    International Nuclear Information System (INIS)

    Cassignol, C.; Ortel, Y.; Taieb, J.

    1950-01-01

    A mass spectrometer for leak detection and rapid gas analysis were constructed, having the characteristics and several structural features of a simple instrument described by Siry in Rev. Sri. Instruments. 540 (1947). Although exhibiting a good resolving power, the apparatus, which has no ion lenses and whose electrodes can be regulated during the performance, has not been sufficiently tested. Since several design defects have been discovered, it will probably be rebuilt with various improvements (ion source outside the magnetic field, modified circuits, etc.). (author)

  15. Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jessica Ann Wojtalik

    2016-01-01

    Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

  16. E-cigarettes: a rapidly growing Internet phenomenon.

    Science.gov (United States)

    Yamin, Cyrus K; Bitton, Asaf; Bates, David W

    2010-11-02

    Electronic cigarettes (e-cigarettes) aerosolize nicotine and produce a vapor that emulates that of cigarettes but purportedly has fewer traditional toxins than secondhand smoke. Although e-cigarettes are widely sold online and by retailers, new research suggests that they may contain unexpected toxins and may provide unreliable nicotine delivery. Many countries have already banned or strictly regulated e-cigarettes. Currently in the United States, e-cigarettes are exempt from regulation as drug-delivery devices. Meanwhile, the presence of e-cigarettes on the Internet, including in Web searches, virtual user communities, and online stores where people sell e-cigarettes on commission, is increasing rapidly. Physicians should be aware of the popularity, questionable efficacy claims, and safety concerns of e-cigarettes so that they may counsel patients against use and advocate for research to inform an evidence-based regulatory approach.

  17. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2012-02-01

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  18. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-03-17

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  19. Characteristics of rapid eye movement sleep behavior disorder in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Frandsen, Rune Asger Vestergaard; Knudsen, Stine

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with Parkinsonian disorders, but is also reported in narcolepsy. Most patients...... of hypocretin deficiency. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Moreover, it is likely that hypocretin deficiency independently predicts periodic limb movements in REM and NREM sleep, probably via involvement...... of the dopaminergic system. This supports the hypothesis that an impaired hypocretin system causes general instability of motor regulation during wakefulness, REM and NREM sleep in human narcolepsy. We propose that hypocretin neurons are centrally involved in motor tone control during wakefulness and sleep in humans...

  20. Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP.

    Science.gov (United States)

    Cravo, Sergio L; Campos, Ruy R; Colombari, Eduardo; Sato, Mônica A; Bergamaschi, Cássia M; Pedrino, Gustavo R; Ferreira-Neto, Marcos L; Lopes, Oswaldo U

    2009-09-01

    Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

  1. Complex regulation controls Neurogenin3 proteolysis

    Directory of Open Access Journals (Sweden)

    Ryan Roark

    2012-10-01

    The ubiquitin proteasome system (UPS is known to be responsible for the rapid turnover of many transcription factors, where half-life is held to be critical for regulation of transcriptional activity. However, the stability of key transcriptional regulators of development is often very poorly characterised. Neurogenin 3 (Ngn3 is a basic helix–loop–helix transcription factor that plays a central role in specification and differentiation of endocrine cells of the pancreas and gut, as well as spermatogonia and regions of the brain. Here we demonstrate that Ngn3 protein stability is regulated by the ubiquitin proteasome system and that Ngn3 can be ubiquitylated on lysines, the N-terminus and, highly unusually, on non-canonical residues including cysteines and serines/threonines. Rapid turnover of Ngn3 is regulated both by binding to its heterodimeric partner E protein and by the presence of cdk inhibitors. We show that protein half-life does appear to regulate the activity of Ngn3 in vivo, but, unlike the related transcription factor c-myc, ubiquitylation on canonical sites is not a requirement for transcriptional activity of Ngn3. Hence, we characterise an important new level of Ngn3 post-translational control, which may regulate its transcriptional activity.

  2. RAPID TRANSFER ALIGNMENT USING FEDERATED KALMAN FILTER

    Institute of Scientific and Technical Information of China (English)

    GUDong-qing; QINYong-yuan; PENGRong; LIXin

    2005-01-01

    The dimension number of the centralized Kalman filter (CKF) for the rapid transfer alignment (TA) is as high as 21 if the aircraft wing flexure motion is considered in the rapid TA. The 21-dimensional CKF brings the calculation burden on the computer and the difficulty to meet a high filtering updating rate desired by rapid TA. The federated Kalman filter (FKF) for the rapid TA is proposed to solve the dilemma. The structure and the algorithm of the FKF, which can perform parallel computation and has less calculation burden, are designed.The wing flexure motion is modeled, and then the 12-order velocity matching local filter and the 15-order attitud ematching local filter are devised. Simulation results show that the proposed EKE for the rapid TA almost has the same performance as the CKF. Thus the calculation burden of the proposed FKF for the rapid TA is markedly decreased.

  3. Theory of hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Del Duca, V.

    1995-06-01

    In this talk we review the models describing the hard diffractive production of jets or more generally high-mass states in presence of rapidity gaps in hadron-hadron and lepton-hadron collisions. By rapidity gaps we mean regions on the lego plot in (pseudo)-rapidity and azimuthal angle where no hadrons are produced, between the jet(s) and an elastically scattered hadron (single hard diffraction) or between two jets (double hard diffraction). (orig.)

  4. Theory of hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Del Duca, V.

    1996-01-01

    In this talk we review the models describing the hard diffractive production of jets or more generally high-mass states in presence of rapidity gaps in hadron-hadron and lepton-hadron collisions. By rapidity gaps we mean regions on the lego plot in (pseudo)-rapidity and azimuthal angle where no hadrons are produced, between the jet(s) and an elastically scattered hadron (single hard diffraction) or between two jets (double hard diffraction). copyright 1996 American Institute of Physics

  5. Parallel, Rapid Diffuse Optical Tomography of Breast

    National Research Council Canada - National Science Library

    Yodh, Arjun

    2001-01-01

    During the last year we have experimentally and computationally investigated rapid acquisition and analysis of informationally dense diffuse optical data sets in the parallel plate compressed breast geometry...

  6. Parallel, Rapid Diffuse Optical Tomography of Breast

    National Research Council Canada - National Science Library

    Yodh, Arjun

    2002-01-01

    During the last year we have experimentally and computationally investigated rapid acquisition and analysis of informationally dense diffuse optical data sets in the parallel plate compressed breast geometry...

  7. Numerology on pion and proton rapidity

    International Nuclear Information System (INIS)

    Gugelot, P.C.

    1987-01-01

    The pseudo-rapidity of pion jets which were measured for 50 GeV and 150 GeV incident pions and protons on carbon, copper and lead targets is analysed. The shape of the rapidity distribution for a ''fireball'' which emits particles isotropically in its center of mass is a cosh -2 y distribution. It is possible to unfold all measured distributions into three groups which correspond to a low rapidity originating from the target fragmentation, a middle group which is a function of the center of mass of the projectile and target rapidity and a fast group which is due to the projectile. 11 refs., 8 figs. (author)

  8. Rapid Automated Mission Planning System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is an automated UAS mission planning system that will rapidly identify emergency (contingency) landing sites, manage contingency routing, and...

  9. Rapid Robot Design Validation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robot designs. The software will support push-button validation...

  10. DIII-D ICRF high voltage power supply regulator upgrade

    International Nuclear Information System (INIS)

    Cary, W.P.; Burley, B.L.; Grosnickle, W.H.

    1997-11-01

    For reliable operation and component protection, of the 2 MW 30--120 MHz ICRF Amplifier System on DIII-D, it is desirable for the amplifier to respond to high VSWR conditions as rapidly as possible. This requires a rapid change in power which also means a rapid change in the high voltage power supply current demands. An analysis of the power supply's regulator dynamics was needed to verify its expected operation during such conditions. Based on this information it was found that a new regulator with a larger dynamic range and some anticipation capability would be required. This paper will discuss the system requirements, the as-delivered regulator performance, and the improved performance after installation of the new regulator system. It will also be shown how this improvement has made the amplifier perform at higher power levels more reliably

  11. Rapid effects of estrogens on short-term memory: Possible mechanisms.

    Science.gov (United States)

    Paletta, Pietro; Sheppard, Paul A S; Matta, Richard; Ervin, Kelsy S J; Choleris, Elena

    2018-06-01

    Estrogens affect learning and memory through rapid and delayed mechanisms. Here we review studies on rapid effects on short-term memory. Estradiol rapidly improves social and object recognition memory, spatial memory, and social learning when administered systemically. The dorsal hippocampus mediates estrogen rapid facilitation of object, social and spatial short-term memory. The medial amygdala mediates rapid facilitation of social recognition. The three estrogen receptors, α (ERα), β (ERβ) and the G-protein coupled estrogen receptor (GPER) appear to play different roles depending on the task and brain region. Both ERα and GPER agonists rapidly facilitate short-term social and object recognition and spatial memory when administered systemically or into the dorsal hippocampus and facilitate social recognition in the medial amygdala. Conversely, only GPER can facilitate social learning after systemic treatment and an ERβ agonist only rapidly improved short-term spatial memory when given systemically or into the hippocampus, but also facilitates social recognition in the medial amygdala. Investigations into the mechanisms behind estrogens' rapid effects on short term memory showed an involvement of the extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K) kinase pathways. Recent evidence also showed that estrogens interact with the neuropeptide oxytocin in rapidly facilitating social recognition. Estrogens can increase the production and/or release of oxytocin and other neurotransmitters, such as dopamine and acetylcholine. Therefore, it is possible that estrogens' rapid effects on short-term memory may occur through the regulation of various neurotransmitters, although more research is need on these interactions as well as the mechanisms of estrogens' actions on short-term memory. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

    Science.gov (United States)

    Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

    2004-04-29

    Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  13. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

    Directory of Open Access Journals (Sweden)

    Golemis Erica A

    2004-04-01

    Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  14. Emotion regulation reduces loss aversion and decreases amygdala responses to losses.

    Science.gov (United States)

    Sokol-Hessner, Peter; Camerer, Colin F; Phelps, Elizabeth A

    2013-03-01

    Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices.

  15. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Schenck, C H; Montplaisir, J Y; Frauscher, B

    2013-01-01

    We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD...

  16. Rapid methods for detection of bacteria

    DEFF Research Database (Denmark)

    Corfitzen, Charlotte B.; Andersen, B.Ø.; Miller, M.

    2006-01-01

    Traditional methods for detection of bacteria in drinking water e.g. Heterotrophic Plate Counts (HPC) or Most Probable Number (MNP) take 48-72 hours to give the result. New rapid methods for detection of bacteria are needed to protect the consumers against contaminations. Two rapid methods...

  17. Rapid 3-D analysis of rockfalls

    Science.gov (United States)

    Stock, Greg M.; Guerin, A.; Avdievitch, Nikita N.; Collins, Brian D.; Jaboyedoff, Michel

    2018-01-01

    Recent fatal and damaging rockfalls in Yosemite National Park indicate the need for rapid response data collection methods to inform public safety and assist with management response. Here we show the use of multiple-platform remote sensing methods to rapidly capture pertinent data needed to inform management and the public following a several large rockfalls from El Capitan cliff in Yosemite Valley, California.

  18. Rapid Prototyping: An Alternative Instructional Design Strategy.

    Science.gov (United States)

    Tripp, Steven D.; Bichelmeyer, Barbara

    1990-01-01

    Discusses the nature of instructional design and describes rapid prototyping as a feasible model for instructional system design (ISD). The use of prototyping in software engineering is described, similarities between software design and instructional design are discussed, and an example is given which uses rapid prototyping in designing a…

  19. A Systems Approach to Rapid School Improvement

    Science.gov (United States)

    McCauley, Carlas

    2018-01-01

    To support systemic thinking about school improvement, the Center on School Turnaround at WestEd developed a framework to assist states, districts, and schools in leading and managing rapid improvement efforts. The framework, which is presented in this article, has four domains that have proved central to rapid, significant improvement: (1)…

  20. Low specificity of 2 tetanus rapid tests in Cambodia.

    Science.gov (United States)

    Schlumberger, M; Yvonnet, B; Lesage, G; Tep, B

    2015-01-01

    Rapid testing for tetanus on serum or blood allows for an immediate evaluation of individual protection against tetanus in developed countries, using a "single step" immunochromatographic technique using tetanus toxoid. The specificity of these tests, compared to the reference method for tetanus, mouse serum neutralization testing, has however never been assessed in these countries, due to the difficulty to perform serum neutralization titration in mice, because of animal testing bioethical regulations. A collection of sera from adult volunteers in Cambodia, living in rural environment, was tested for tetanus antibodies by ELISA in France, and by mouse serum neutralization in Vietnam. This allowed estimating the sensitivity and specificity of 2 rapid tetanus tests, available on the market: TQS™ and Tetanotop™. The sensitivity of these tests was adequate, compared to mice serum neutralization test, for a test threshold of 0.01 IU/mL, (100% for TQS™, 91% for Tetanotop™), but their specificity was very low (1% for TQS™ and 13% for Tetanotop™). The results prove that these rapid tests for the assessment of individual protection against tetanus should not be used in the adult rural Cambodian population. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. On being a scientist in a rapidly changing world.

    Science.gov (United States)

    Mandel, I D

    1996-02-01

    The practice of biological science has changed dramatically since mid-century, reshaped not only by a rapid series of landmark discoveries, but also by governmental directives, institutional policies, and public attitudes. Until 1964, the major influences were the mentor, who provided direction and indoctrination into the culture of science, and in dentistry, the newly established NIDR, which fueled the research engine with an expanding research and training program. The 1965-74 period witnessed the advent of the Institutional Review Board, an increased social involvement of biological scientists, and a recognition of the need for biological and physical safeguards in the conduct of research. The most turbulent years were 1975-89, when there was a confluence of animal rights activism and regulation, growing concerns with scientific fraud and publication malpractice, and the stresses and strains (and opportunities) resulting from the rapid expansion of the academic-industrial complex. The current period is characterized by rapid pace, high volume, and an increased depth and breadth of knowledge-a major change in scale in the conduct of science. It is an exciting time but one in which ethical issues are multiplying. Attention must be paid.

  2. Competition between bank regulators

    OpenAIRE

    Schindler, Dirk; Eggert, Wolfgang

    2004-01-01

    This paper examines competition between bank regulators in open economies. We use a model where credit demand of firms is endogenous and show any tendency for downward competition in regulation policy is limited by the effect of regulation on profits of nonfinancial firms. Moreover, perfect mobility on loans and deposit markets fully eliminates the incentives of regulators to set bank regulation at ine±cient low levels.

  3. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS: a commentary

    Directory of Open Access Journals (Sweden)

    Waite Roger L

    2008-11-01

    Full Text Available Abstract Background and hypothesis Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc dopamine receptors (D1-D5, whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing

  4. Rapid dopaminergic modulation of the fish hypothalamic transcriptome and proteome.

    Directory of Open Access Journals (Sweden)

    Jason T Popesku

    2010-08-01

    Full Text Available Dopamine (DA is a major neurotransmitter playing an important role in the regulation of vertebrate reproduction. We developed a novel method for the comparison of transcriptomic and proteomic data obtained from in vivo experiments designed to study the neuroendocrine actions of DA.Female goldfish were injected (i.p. with DA agonists (D1-specific; SKF 38393, or D2-specific; LY 171555 and sacrificed after 5 h. Serum LH levels were reduced by 57% and 75% by SKF 38393 and LY 171555, respectively, indicating that the treatments produced physiologically relevant responses in vivo. Bioinformatic strategies and a ray-finned fish database were established for microarray and iTRAQ proteomic analysis of the hypothalamus, revealing a total of 3088 mRNAs and 42 proteins as being differentially regulated by the treatments. Twenty one proteins and mRNAs corresponding to these proteins appeared on both lists. Many of the mRNAs and proteins affected by the treatments were grouped into the Gene Ontology categorizations of protein complex, signal transduction, response to stimulus, and regulation of cellular processes. There was a 57% and 14% directional agreement between the differentially-regulated mRNAs and proteins for SKF 38393 and LY 171555, respectively.The results demonstrate the applicability of advanced high-throughput genomic and proteomic analyses in an amendable well-studied teleost model species whose genome has yet to be sequenced. We demonstrate that DA rapidly regulates multiple hypothalamic pathways and processes that are also known to be involved in pathologies of the central nervous system.

  5. Regulating through leverage: Civil regulation in China

    NARCIS (Netherlands)

    Fürst, K.

    2016-01-01

    The overarching goal of this study is to examine the efforts of Chinese NGOs to prevent and/or control industrial pollution risks and then use the findings of this research to study the nature of civil regulation in, and beyond, China’s authoritarian setting. It first argues that 'regulation through

  6. Risks and Benefits of Rapid Clozapine Titration.

    Science.gov (United States)

    Lochhead, Jeannie D; Nelson, Michele A; Schneider, Alan L

    2016-05-18

    Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  7. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  8. Risks and benefits of rapid clozapine titration

    Directory of Open Access Journals (Sweden)

    Jeannie D. Lochhead

    2016-05-01

    Full Text Available Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  9. A scoping review of rapid review methods.

    Science.gov (United States)

    Tricco, Andrea C; Antony, Jesmin; Zarin, Wasifa; Strifler, Lisa; Ghassemi, Marco; Ivory, John; Perrier, Laure; Hutton, Brian; Moher, David; Straus, Sharon E

    2015-09-16

    Rapid reviews are a form of knowledge synthesis in which components of the systematic review process are simplified or omitted to produce information in a timely manner. Although numerous centers are conducting rapid reviews internationally, few studies have examined the methodological characteristics of rapid reviews. We aimed to examine articles, books, and reports that evaluated, compared, used or described rapid reviews or methods through a scoping review. MEDLINE, EMBASE, the Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. We included 100 articles plus one companion report that were published between 1997 and 2013. The studies were categorized as 84 application papers, seven development papers, six impact papers, and four comparison papers (one was included in two categories). The rapid reviews were conducted between 1 and 12 months, predominantly in Europe (58 %) and North America (20 %). The included studies failed to report 6 % to 73 % of the specific systematic review steps examined. Fifty unique rapid review methods were identified; 16 methods occurred more than once. Streamlined methods that were used in the 82 rapid reviews included limiting the literature search to published literature (24 %) or one database (2 %), limiting inclusion criteria by date (68 %) or language (49 %), having one person screen and another verify or screen excluded studies (6 %), having one person abstract data and another verify (23 %), not conducting risk of bias/quality appraisal (7 %) or having only one reviewer conduct the quality appraisal (7 %), and presenting results as a narrative summary (78 %). Four case studies were identified that compared the results of rapid reviews to systematic reviews. Three studies found that the conclusions between

  10. Economic analyses of rapid population growth.

    Science.gov (United States)

    Birdsall, N

    1989-01-01

    "Discussion of the macroeconomic consequences of rapid population growth is organized into three schools: pessimists, optimists, and the recent revisionists. For the revisionists, differing views are presented about the pervasiveness and relevance of market failures, such as the negative externalities of childbearing, and about the ability of families and institutions to adjust rapidly to changes brought on by rapid population growth. A welfare economics approach is used to review the merits of various public policies to reduce fertility, including public financing of family planning services and taxes and incentives associated with childbearing." The focus is on developing countries. excerpt

  11. Cation distributions on rapidly solidified cobalt ferrite

    Science.gov (United States)

    De Guire, Mark R.; Kalonji, Gretchen; O'Handley, Robert C.

    1990-01-01

    The cation distributions in two rapidly solidified cobalt ferrites have been determined using Moessbauer spectroscopy at 4.2 K in an 8-T magnetic field. The samples were obtained by gas atomization of a Co0-Fe2O3-P2O5 melt. The degree of cation disorder in both cases was greater than is obtainable by cooling unmelted cobalt ferrite. The more rapidly cooled sample exhibited a smaller departure from the equilibrium cation distribution than did the more slowly cooled sample. This result is explained on the basis of two competing effects of rapid solidification: high cooling rate of the solid, and large undercooling.

  12. [Rapid prototyping: a very promising method].

    Science.gov (United States)

    Haverman, T M; Karagozoglu, K H; Prins, H-J; Schulten, E A J M; Forouzanfar, T

    2013-03-01

    Rapid prototyping is a method which makes it possible to produce a three-dimensional model based on two-dimensional imaging. Various rapid prototyping methods are available for modelling, such as stereolithography, selective laser sintering, direct laser metal sintering, two-photon polymerization, laminated object manufacturing, three-dimensional printing, three-dimensional plotting, polyjet inkjet technology,fused deposition modelling, vacuum casting and milling. The various methods currently being used in the biomedical sector differ in production, materials and properties of the three-dimensional model which is produced. Rapid prototyping is mainly usedforpreoperative planning, simulation, education, and research into and development of bioengineering possibilities.

  13. Rapid Multiplex Microbial Detector, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid nucleic acid-based detector for spaceflight water systems to enable simultaneous quantification of multiple...

  14. simple and rapid spectrophotometric assay of levocetirizine

    African Journals Online (AJOL)

    Preferred Customer

    Simple, rapid, selective and fairly sensitive method is described for the ... Determination of small amounts of LCTZ in pharmaceutical preparations is important for .... sodium hydroxide and extraction of HCl-free-amine into chloroform followed ...

  15. Rapid Update Cycle (RUC) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Update Cycle (RUC) weather forecast model was developed by the National Centers for Environmental Prediction (NCEP). On May 1, 2012, the RUC was replaced...

  16. The Rapid Perceptual Impact of Emotional Distractors.

    Directory of Open Access Journals (Sweden)

    Briana L Kennedy

    Full Text Available The brief presentation of an emotional distractor can temporarily impair perception of a subsequent, rapidly presented target, an effect known as emotion-induced blindness (EIB. How rapidly does this impairment unfold? To probe this question, we examined EIB for targets that immediately succeeded ("lag-1" emotional distractors in a rapid stream of items relative to EIB for targets at later serial positions. Experiments 1 and 2 suggested that emotional distractors interfere with items presented very soon after them, with impaired target perception emerging as early as lag-1. Experiment 3 included an exploratory examination of individual differences, which suggested that EIB onsets more rapidly among participants scoring high in measures linked to negative affect.

  17. Mars Sample Return Orbiter Rapid Architecture Study

    Science.gov (United States)

    Godfrey, A.; Johnson, M.; Stroud, C.

    2018-04-01

    An overview of rapid systems analysis (mass, risk, and schedule) on 1000s of MSRO configurations to understand key technologies and feasible options. Can we generate enough power? Can we aerobrake in time? Are some technology elements just too risky?

  18. Rapid Update Cycle (RUC) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Update Cycle (RUC) weather forecast model was developed by the National Centers for Environmental Prediction (NCEP). On May 1, 2012, the RUC was replaced...

  19. A Rapid Coliform Detector, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid genetic detector for spaceflight water systems to enable real-time detection of E-coli with minimal...

  20. Exploring data with RapidMiner

    CERN Document Server

    Chisholm, Andrew

    2013-01-01

    A step-by-step tutorial style using examples so that users of different levels will benefit from the facilities offered by RapidMiner.If you are a computer scientist or an engineer who has real data from which you want to extract value, this book is ideal for you. You will need to have at least a basic awareness of data mining techniques and some exposure to RapidMiner.

  1. Clan structure analysis and rapidity gap probability

    International Nuclear Information System (INIS)

    Lupia, S.; Giovannini, A.; Ugoccioni, R.

    1995-01-01

    Clan structure analysis in rapidity intervals is generalized from negative binomial multiplicity distribution to the wide class of compound Poisson distributions. The link of generalized clan structure analysis with correlation functions is also established. These theoretical results are then applied to minimum bias events and evidentiate new interesting features, which can be inspiring and useful in order to discuss data on rapidity gap probability at TEVATRON and HERA. (orig.)

  2. Clan structure analysis and rapidity gap probability

    Energy Technology Data Exchange (ETDEWEB)

    Lupia, S. [Turin Univ. (Italy). Ist. di Fisica Teorica]|[Istituto Nazionale di Fisica Nucleare, Turin (Italy); Giovannini, A. [Turin Univ. (Italy). Ist. di Fisica Teorica]|[Istituto Nazionale di Fisica Nucleare, Turin (Italy); Ugoccioni, R. [Turin Univ. (Italy). Ist. di Fisica Teorica]|[Istituto Nazionale di Fisica Nucleare, Turin (Italy)

    1995-03-01

    Clan structure analysis in rapidity intervals is generalized from negative binomial multiplicity distribution to the wide class of compound Poisson distributions. The link of generalized clan structure analysis with correlation functions is also established. These theoretical results are then applied to minimum bias events and evidentiate new interesting features, which can be inspiring and useful in order to discuss data on rapidity gap probability at TEVATRON and HERA. (orig.)

  3. Characterization of aluminium alloys rapidly solidified

    International Nuclear Information System (INIS)

    Monteiro, W.A.

    1988-01-01

    This paper discussed the investigation of the microstructural and mechanical properties of the aluminium alloys (3003; 7050; Al-9% Mg) rapidly solidified by melt spinning process (cooling rate 10 4 - 10 6 K/s). The rapidly solidification process of the studied aluminium alloys brought a microcrystallinity, a minimum presence of coarse precipitation and, also, better mechanical properties of them comparing to the same alloys using ingot process. (author) [pt

  4. Rapidly curable electrically conductive clear coatings

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Mark P.; Anderson, Lawrence G.; Post, Gordon L.

    2018-01-16

    Rapidly curable electrically conductive clear coatings are applied to substrates. The electrically conductive clear coating includes to clear layer having a resinous binder with ultrafine non-stoichiometric tungsten oxide particles dispersed therein. The clear coating may be rapidly cured by subjecting the coating to infrared radiation that heats the tungsten oxide particles and surrounding resinous binder. Localized heating increases the temperature of the coating to thereby thermally cure the coating, while avoiding unwanted heating of the underlying substrate.

  5. Rapid modification of retroviruses using lipid conjugates

    International Nuclear Information System (INIS)

    Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

    2009-01-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  6. Sensory integration regulating male courtship behavior in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dimitrije Krstic

    Full Text Available The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i between initiation and maintenance of courtship, (ii between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior.

  7. Regulation of the mesolimbic dopamine circuit by feeding peptides.

    Science.gov (United States)

    Liu, S; Borgland, S L

    2015-03-19

    Polypeptides produced in the gastrointestinal tract, stomach, adipocytes, pancreas and brain that influence food intake are referred to as 'feeding-related' peptides. Most peptides that influence feeding exert an inhibitory effect (anorexigenic peptides). In contrast, only a few exert a stimulating effect (orexigenic peptides), such as ghrelin. Homeostatic feeding refers to when food consumed matches energy deficits. However, in western society where access to palatable energy-dense food is nearly unlimited, food is mostly consumed for non-homeostatic reasons. Emerging evidence implicates the mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), as a key substrate for non-homeostatic feeding. VTA dopamine neurons encode cues that predict rewards and phasic release of dopamine in the ventral striatum motivates animals to forage for food. To elucidate how feeding-related peptides regulate reward pathways is of importance to reveal the mechanisms underlying non-homeostatic or hedonic feeding. Here, we review the current knowledge of how anorexigenic peptides and orexigenic peptides act within the VTA. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Review on CNC-Rapid Prototyping

    International Nuclear Information System (INIS)

    M Nafis O Z; Nafrizuan M Y; Munira M A; Kartina J

    2012-01-01

    This article reviewed developments of Computerized Numerical Control (CNC) technology in rapid prototyping process. Rapid prototyping (RP) can be classified into three major groups; subtractive, additive and virtual. CNC rapid prototyping is grouped under the subtractive category which involves material removal from the workpiece that is larger than the final part. Richard Wysk established the use of CNC machines for rapid prototyping using sets of 2½-D tool paths from various orientations about a rotary axis to machine parts without refixturing. Since then, there are few developments on this process mainly aimed to optimized the operation and increase the process capabilities to stand equal with common additive type of RP. These developments include the integration between machining and deposition process (hybrid RP), adoption of RP to the conventional machine and optimization of the CNC rapid prototyping process based on controlled parameters. The article ended by concluding that the CNC rapid prototyping research area has a vast space for improvement as in the conventional machining processes. Further developments and findings will enhance the usage of this method and minimize the limitation of current approach in building a prototype.

  9. Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder.

    Science.gov (United States)

    Goodman, Marianne; Carpenter, David; Tang, Cheuk Y; Goldstein, Kim E; Avedon, Jennifer; Fernandez, Nicolas; Mascitelli, Kathryn A; Blair, Nicholas J; New, Antonia S; Triebwasser, Joseph; Siever, Larry J; Hazlett, Erin A

    2014-10-01

    Siever and Davis' (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity-part of the disturbed neural circuitry underlying emotional dysregulation

  10. Atomic Energy Control Regulations

    International Nuclear Information System (INIS)

    1992-01-01

    This is the consolidated text of the Atomic Energy Control Regulations of 17 March 1960, with amendments to 27 August 1992. The Regulations cover the licensing of nuclear facilities, radiation sources, including uranium mining, radiation protection questions, etc. (NEA)

  11. Environmental regulation and competitiveness

    NARCIS (Netherlands)

    Mulatu, A.; Florax, R.J.G.M.; Withagen, C.A.A.M.

    2001-01-01

    The potential relationship between domestic environmental regulation and international competitiveness has evoked various speculations. The common neoclassical train of thought is that strict environmental regulation is detrimental to the competitiveness of industry, and that it induces phenomena

  12. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    1978-01-01

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  13. Regulation of Genetic Tests

    Science.gov (United States)

    ... for Genomics Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ...

  14. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  15. Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

    Science.gov (United States)

    Aznar, Susana; Klein, Anders B

    2013-12-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

  16. Culture and emotion regulation.

    Science.gov (United States)

    Ford, Brett Q; Mauss, Iris B

    2015-06-01

    While anthropological research has long emphasized cultural differences in whether emotions are viewed as beneficial versus harmful, psychological science has only recently begun to systematically examine those differences and their implications for emotion regulation and well-being. Underscoring the pervasive role of culture in people's emotions, we summarize research that has examined links between culture, emotion regulation, and well-being. Specifically, we focus on two questions. First, how does culture lead individuals to regulate their emotions? And second, how does culture modulate the link between emotion regulation and well-being? We finish by suggesting directions for future research to advance the study of culture and emotion regulation.

  17. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    1993-01-01

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  18. Load regulating expansion fixture

    International Nuclear Information System (INIS)

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  19. Rapid enzymatic response to compensate UV radiation in copepods.

    Directory of Open Access Journals (Sweden)

    María Sol Souza

    Full Text Available Ultraviolet radiation (UVR causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST, that regulate apoptosis cell death (Caspase-3, Casp-3, and that facilitate neurotransmissions (cholinesterase-ChE. None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales.

  20. Rapid, Reliable Shape Setting of Superelastic Nitinol for Prototyping Robots.

    Science.gov (United States)

    Gilbert, Hunter B; Webster, Robert J

    Shape setting Nitinol tubes and wires in a typical laboratory setting for use in superelastic robots is challenging. Obtaining samples that remain superelastic and exhibit desired precurvatures currently requires many iterations, which is time consuming and consumes a substantial amount of Nitinol. To provide a more accurate and reliable method of shape setting, in this paper we propose an electrical technique that uses Joule heating to attain the necessary shape setting temperatures. The resulting high power heating prevents unintended aging of the material and yields consistent and accurate results for the rapid creation of prototypes. We present a complete algorithm and system together with an experimental analysis of temperature regulation. We experimentally validate the approach on Nitinol tubes that are shape set into planar curves. We also demonstrate the feasibility of creating general space curves by shape setting a helical tube. The system demonstrates a mean absolute temperature error of 10°C.

  1. Volume regulation in epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    to amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...... volume regulation. In the same cell, these functions may be maintained by different ion pathways that are separately regulated. RVD is often preceded by increase in cytosolic free Ca2+, probably via influx through TRP channels, but Ca2+ release from intracellular stores has also been observed. Cell...

  2. Voltage regulator for generator

    Energy Technology Data Exchange (ETDEWEB)

    Naoi, K

    1989-01-17

    It is an object of this invention to provide a voltage regulator for a generator charging a battery, wherein even if the ambient temperature at the voltage regulator rises abnormally high, possible thermal breakage of the semiconductor elements constituting the voltage regulator can be avoided. A feature of this invention is that the semiconductor elements can be protected from thermal breakage, even at an abnormal ambient temperature rise at the voltage regulator for the battery charging generator, by controlling a maximum conduction ratio of a power transistor in the voltage regulator in accordance with the temperature at the voltage regulator. This is achieved through a switching device connected in series to the field coil of the generator and adapted to be controlled in accordance with an output voltage of the generator and the ambient temperature at the voltage regulator. 6 figs.

  3. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian; Wu, Junhua

    2012-01-01

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses

  4. Rapid, generalized adaptation to asynchronous audiovisual speech.

    Science.gov (United States)

    Van der Burg, Erik; Goodbourn, Patrick T

    2015-04-07

    The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  5. Rapid-Sequence Serial Sexual Homicides.

    Science.gov (United States)

    Schlesinger, Louis B; Ramirez, Stephanie; Tusa, Brittany; Jarvis, John P; Erdberg, Philip

    2017-03-01

    Serial sexual murderers have been described as committing homicides in a methodical manner, taking substantial time between offenses to elude the authorities. The results of our study of the temporal patterns (i.e., the length of time between homicides) of a nonrandom national sample of 44 serial sexual murderers and their 201 victims indicate that this representation may not always be accurate. Although 25 offenders (56.8%) killed with longer than a 14-day period between homicides, a sizeable subgroup was identified: 19 offenders (43.2%) who committed homicides in rapid-sequence fashion, with fewer than 14 days between all or some of the murders. Six offenders (13.6%) killed all their victims in one rapid-sequence, spree-like episode, with homicides just days apart or sometimes two murders in the same day. Thirteen offenders (29.5%) killed in one or two rapid-sequence clusters (i.e., more than one murder within a 14-day period, as well as additional homicides with greater than 14 days between each). The purpose of our study was to describe this subgroup of rapid-sequence offenders who have not been identified until now. These findings argue for accelerated forensic assessments of dangerousness and public safety when a sexual murder is detected. Psychiatric disorders with rapidly occurring symptom patterns, or even atypical mania or mood dysregulation, may serve as exemplars for understanding this extraordinary group of offenders. © 2017 American Academy of Psychiatry and the Law.

  6. Rapid penetration into granular media visualizing the fundamental physics of rapid earth penetration

    CERN Document Server

    Iskander, Magued

    2015-01-01

    Rapid Penetration into Granular Media: Visualizing the Fundamental Physics of Rapid Earth Penetration introduces readers to the variety of methods and techniques used to visualize, observe, and model the rapid penetration of natural and man-made projectiles into earth materials. It provides seasoned practitioners with a standard reference that showcases the topic's most recent developments in research and application. The text compiles the findings of new research developments on the subject, outlines the fundamental physics of rapid penetration into granular media, and assembles a com

  7. Addiction Circuitry in the Human Brain*

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo

    2011-01-01

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person’s risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circ...

  8. Adaptive Pulvinar Circuitry Supports Visual Cognition.

    Science.gov (United States)

    Bridge, Holly; Leopold, David A; Bourne, James A

    2016-02-01

    The pulvinar is the largest thalamic nucleus in primates and one of the most mysterious. Endeavors to understand its role in vision have focused on its abundant connections with the visual cortex. While its connectivity mapping in the cortex displays a broad topographic organization, its projections are also marked by considerable convergence and divergence. As a result, the pulvinar is often regarded as a central forebrain hub. Moreover, new evidence suggests that its comparatively modest input from structures such as the retina and superior colliculus may critically shape the functional organization of the visual cortex, particularly during early development. Here we review recent studies that cast fresh light on how the many convergent pathways through the pulvinar contribute to visual cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Neural circuitry for rat recognition memory

    Science.gov (United States)

    Warburton, E.C.; Brown, M.W.

    2015-01-01

    Information concerning the roles of different brain regions in recognition memory processes is reviewed. The review concentrates on findings from spontaneous recognition memory tasks performed by rats, including memory for single objects, locations, object–location associations and temporal order. Particular emphasis is given to the potential roles of different regions in the circuit of interacting structures involving the perirhinal cortex, hippocampus, medial prefrontal cortex and medial dorsal thalamus in recognition memory for the association of objects and places. It is concluded that while all structures in this circuit play roles critical to such memory, these roles can potentially be differentiated and differences in the underlying synaptic and biochemical processes involved in each region are beginning to be uncovered. PMID:25315129

  10. Addiction circuitry in the human brain (*).

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  11. Rapid resensitization of purinergic receptor function in human platelets.

    Science.gov (United States)

    Mundell, S J; Barton, J F; Mayo-Martin, M B; Hardy, A R; Poole, A W

    2008-08-01

    Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors (GPCRs), the P2Y(1) and P2Y(12) purinergic receptors. Recently, we demonstrated that both receptors desensitize and internalize in human platelets by differential kinase-dependent mechanisms. To demonstrate whether responses to P2Y(1) and P2Y(12) purinergic receptors resensitize in human platelets and determine the role of receptor traffic in this process. These studies were undertaken either in human platelets or in cells stably expressing epitope-tagged P2Y(1) and P2Y(12) purinergic receptor constructs. In this study we show for the first time that responses to both of these receptors can rapidly resensitize following agonist-dependent desensitization in human platelets. Further, we show that in human platelets or in 1321N1 cells stably expressing receptor constructs, the disruption of receptor internalization, dephosphorylation or subsequent receptor recycling is sufficient to block resensitization of purinergic receptor responses. We also show that, in platelets, internalization of both these receptors is dependent upon dynamin, and that this process is required for resensitization of responses. This study is therefore the first to show that both P2Y(1) and P2Y(12) receptor activities are rapidly and reversibly modulated in human platelets, and it reveals that the underlying mechanism requires receptor trafficking as an essential part of this process.

  12. Rapid Enzymatic Method for Pectin Methyl Esters Determination

    Directory of Open Access Journals (Sweden)

    Lucyna Łękawska-Andrinopoulou

    2013-01-01

    Full Text Available Pectin is a natural polysaccharide used in food and pharma industries. Pectin degree of methylation is an important parameter having significant influence on pectin applications. A rapid, fully automated, kinetic flow method for determination of pectin methyl esters has been developed. The method is based on a lab-made analyzer using the reverse flow-injection/stopped flow principle. Methanol is released from pectin by pectin methylesterase in the first mixing coil. Enzyme working solution is injected further downstream and it is mixed with pectin/pectin methylesterase stream in the second mixing coil. Methanol is oxidized by alcohol oxidase releasing formaldehyde and hydrogen peroxide. This reaction is coupled to horse radish peroxidase catalyzed reaction, which gives the colored product 4-N-(p-benzoquinoneimine-antipyrine. Reaction rate is proportional to methanol concentration and it is followed using Ocean Optics USB 2000+ spectrophotometer. The analyzer is fully regulated by a lab written LabVIEW program. The detection limit was 1.47 mM with an analysis rate of 7 samples h−1. A paired t-test with results from manual method showed that the automated method results are equivalent to the manual method at the 95% confidence interval. The developed method is rapid and sustainable and it is the first application of flow analysis in pectin analysis.

  13. Rapidity gap survival in enhanced Pomeron scheme

    Energy Technology Data Exchange (ETDEWEB)

    Ostapchenko, Sergey [Frankfurt Institute for Advanced Studies, Frankfurt am Main (Germany); Moscow State University, D.V. Skobeltsyn Institute of Nuclear Physics, Moscow (Russian Federation); Bleicher, Marcus [Frankfurt Institute for Advanced Studies, Frankfurt am Main (Germany); Goethe-Universitat, Institute for Theoretical Physics, Frankfurt am Main (Germany)

    2018-01-15

    We apply the phenomenological Reggeon field theory framework to investigate rapidity gap survival (RGS) probability for diffractive dijet production in proton-proton collisions. In particular, we study in some detail rapidity gap suppression due to elastic rescatterings of intermediate partons in the underlying parton cascades, described by enhanced (Pomeron-Pomeron interaction) diagrams. We demonstrate that such contributions play a subdominant role, compared to the usual, so-called ''eikonal'', rapidity gap suppression due to elastic rescatterings of constituent partons of the colliding protons. On the other hand, the overall RGS factor proves to be sensitive to color fluctuations in the proton. Hence, experimental data on diffractive dijet production can be used to constrain the respective model approaches. (orig.)

  14. Rapid Quench in an Electrostatic Levitator

    Science.gov (United States)

    SanSoucie, Michael P.; Rogers, Jan R.; Matson, Douglas M.

    2016-01-01

    The Electrostatic Levitation (ESL) Laboratory at the NASA Marshall Space Flight Center (MSFC) is a unique facility for investigators studying high-temperature materials. The ESL laboratory's main chamber has been upgraded with the addition of a rapid quench system. This system allows samples to be dropped into a quench vessel that can be filled with a low melting point material, such as a gallium or indium alloy, as a quench medium. Thereby allowing rapid quenching of undercooled liquid metals. Up to eight quench vessels can be loaded into a wheel inside the chamber that is indexed with control software. The system has been tested successfully with samples of zirconium, iron-cobalt alloys, titanium-zirconium-nickel alloys, and a silicon-cobalt alloy. This new rapid quench system will allow materials science studies of undercooled materials and new materials development. In this presentation, the system is described and some initial results are presented.

  15. We really need to talk: adapting FDA processes to rapid change.

    Science.gov (United States)

    Lykken, Sara

    2013-01-01

    The rapidly evolving realm of modern commerce strains traditional regulatory paradigms. This paper traces the historical evolution of FDA crisis-response regulation and provides examples of ways in which the definitions and procedures resulting from that past continue to be challenged by new products as market entrants, some in good faith and others not, take actions that create disconnects between actual product and marketing controls and those that consumers might expect. The paper then explores some of the techniques used by other federal agencies that have faced similar challenges in environments characterized by rapid innovation, and draws from this analysis suggestions for improvement of the FDA's warning letter system.

  16. Rapid web development using AJAX and Python

    Energy Technology Data Exchange (ETDEWEB)

    Dolgert, A; Gibbons, L; Kuznetsov, V [Cornell University, Ithaca, NY 14853 (United States)], E-mail: vkuznet@gmail.com

    2008-07-15

    We discuss the rapid development of a large scale data discovery service for the CMS experiment using modern AJAX techniques and the Python language. To implement a flexible interface capable of accommodating several different versions of the DBS database, we used a 'stack' approach. Asynchronous JavaScript and XML (AJAX) together with an SQL abstraction layer, template engine, code generation tool and dynamic queries provide powerful tools for constructing interactive interfaces to large amounts of data. We show how the use of these tools, with rapid development in a modern scripting language, improved the scalability and usability of the the search interface for different user communities.

  17. Rapid web development using AJAX and Python

    International Nuclear Information System (INIS)

    Dolgert, A; Gibbons, L; Kuznetsov, V

    2008-01-01

    We discuss the rapid development of a large scale data discovery service for the CMS experiment using modern AJAX techniques and the Python language. To implement a flexible interface capable of accommodating several different versions of the DBS database, we used a 'stack' approach. Asynchronous JavaScript and XML (AJAX) together with an SQL abstraction layer, template engine, code generation tool and dynamic queries provide powerful tools for constructing interactive interfaces to large amounts of data. We show how the use of these tools, with rapid development in a modern scripting language, improved the scalability and usability of the the search interface for different user communities

  18. Rapid prototyping using robot welding : process description

    OpenAIRE

    Ribeiro, António Fernando; Norrish, John

    1997-01-01

    Rapid Prototyping is a relatively recent technique to produce component prototypes for industry in a much shorter period of time, since the time to market a product is essential to its success. A new Rapid Prototyping process which uses metal as the raw material had been under development at Cranfield University in the last few years. The process uses a Gas Metal Arc fusion welding robot which deposits successive layers of metal in such way that it forms a 3D solid component. Firstly, a CAD s...

  19. Rapid serial visual presentation design for cognition

    CERN Document Server

    Spence, Robert

    2013-01-01

    A powerful new image presentation technique has evolved over the last twenty years, and its value demonstrated through its support of many and varied common tasks. Conceptually, Rapid Serial Visual Presentation (RSVP) is basically simple, exemplified in the physical world by the rapid riffling of the pages of a book in order to locate a known image. Advances in computation and graphics processing allow RSVP to be applied flexibly and effectively to a huge variety of common tasks such as window shopping, video fast-forward and rewind, TV channel selection and product browsing. At its heart is a

  20. Rapid Gamma Screening of Shipments of Analytical Samples to Meet DOT Regulations

    International Nuclear Information System (INIS)

    Wojtaszek, P.A.; Remington, D.L.; Ideker-Mulligan, V.

    2006-01-01

    The accelerated closure program at Rocky Flats required the capacity to ship up to 1000 analytical samples per week to off-site commercial laboratories, and to conduct such shipment within 24 hours of sample collection. During a period of near peak activity in the closure project, a regulatory change significantly increased the level of radionuclide data required for shipment of each package. In order to meet these dual challenges, a centralized and streamlined sample management program was developed which channeled analytical samples through a single, high-throughput radiological screening facility. This trailerized facility utilized high purity germanium (HPGe) gamma spectrometers to conduct screening measurements of entire packages of samples at once, greatly increasing throughput compared to previous methods. The In Situ Object Counting System (ISOCS) was employed to calibrate the HPGe systems to accommodate the widely varied sample matrices and packing configurations encountered. Optimum modeling and configuration parameters were determined. Accuracy of the measurements of grouped sample jars was confirmed with blind samples in multiple configurations. Levels of radionuclides not observable by gamma spectroscopy were calculated utilizing a spreadsheet program that can accommodate isotopic ratios for large numbers of different waste streams based upon acceptable knowledge. This program integrated all radionuclide data and output all information required for shipment, including the shipping class of the package. (authors)

  1. Disulphide production by Ero1a-PDI relay is rapid and effectively regulated

    DEFF Research Database (Denmark)

    Appenzeller-Herzog, Christian; Riemer, Jan; Zito, Ester

    2010-01-01

    The molecular networks that control endoplasmic reticulum (ER) redox conditions in mammalian cells are incompletely understood. Here, we show that after reductive challenge the ER steady-state disulphide content is restored on a time scale of seconds. Both the oxidase Ero1a and the oxidoreductase...

  2. Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases

    Science.gov (United States)

    Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...

  3. Rapid changes in gene expression: DNA determinants of promoter regulation by the

    Czech Academy of Sciences Publication Activity Database

    Sojka, Luděk; Kouba, Tomáš; Barvík, I.; Šanderová, Hana; Maderová, Zdeňka; Jonák, Jiří; Krásný, Libor

    2011-01-01

    Roč. 39, č. 11 (2011), s. 4598-4611 ISSN 0305-1048 R&D Projects: GA MŠk 2B06065 Institutional research plan: CEZ:AV0Z50200510 Keywords : RIBOSOMAL-RNA TRANSCRIPTION * ILV-LEU OPERON * CHAIN AMINO-ACIDS Subject RIV: EE - Microbiology, Virology Impact factor: 8.026, year: 2011

  4. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  5. The development of regulations

    International Nuclear Information System (INIS)

    Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

    2003-01-01

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

  6. Rapid Isolation and Molecular Detection of Streptomycin-Producing Streptomycetes

    Directory of Open Access Journals (Sweden)

    M Motovali-bashi

    2006-07-01

    Full Text Available Introduction: Streptomyces species are mycelial, aerobic gram-positive bacteria that are isolated from soil and produce a diverse range of antibiotics. Streptomyces griseus produces the antibiotic, streptomycin and forms spores even in a liquid culture. The gene cluster for the production of Streptomycin antibiotic contains strR gene that encodes StrR, a pathway-specific regulator. Then, this pathway-specific regulator induces transcription of other streptomycin production genes in the gene cluster. The overall aim of this work was rapid isolation and molecular detection of streptomycin-producing Streptomycetes, especially S. griseus, from Iranian soils in order to manipulate them for increased production of streptomycin. Methods: This research used new initiative half-specific medium for isolation of Streptomycetes from natural environments, called FZmsn. The fifty colonies of Streptomyces strains grown on the surface of FZmsn medium isolated from environmental samples were defined on the basis of their morphological characteristics and light microscope studies. A set of primers was designed to detect strR by OLIGO software. Results: In colony-PCR reactions followed by gel electrophoresis, 6 colonies from Streptomyces strains colonies were detected as S. griseus colonies. Conclusion: These native Streptomyces strains will be used for genetic manipulation of S. griseus in order to increase production levels of streptomycin.

  7. Developing rapid methods for analyzing upland riparian functions and values.

    Science.gov (United States)

    Hruby, Thomas

    2009-06-01

    Regulators protecting riparian areas need to understand the integrity, health, beneficial uses, functions, and values of this resource. Up to now most methods providing information about riparian areas are based on analyzing condition or integrity. These methods, however, provide little information about functions and values. Different methods are needed that specifically address this aspect of riparian areas. In addition to information on functions and values, regulators have very specific needs that include: an analysis at the site scale, low cost, usability, and inclusion of policy interpretations. To meet these needs a rapid method has been developed that uses a multi-criteria decision matrix to categorize riparian areas in Washington State, USA. Indicators are used to identify the potential of the site to provide a function, the potential of the landscape to support the function, and the value the function provides to society. To meet legal needs fixed boundaries for assessment units are established based on geomorphology, the distance from "Ordinary High Water Mark" and different categories of land uses. Assessment units are first classified based on ecoregions, geomorphic characteristics, and land uses. This simplifies the data that need to be collected at a site, but it requires developing and calibrating a separate model for each "class." The approach to developing methods is adaptable to other locations as its basic structure is not dependent on local conditions.

  8. Regulating hedge funds.

    OpenAIRE

    Daníelsson, J.; Zigrand, JP.

    2007-01-01

    Due to the ever-increasing amounts under management and their unregulated and opaque nature, hedge funds have emerged as a key concern for policymakers. While until now, hedge funds have been left essentially unregulated, we are seeing increasing calls for regulation for both microprudential and macroprudential reasons. In our view, most calls for the regulation of hedge funds are based on a misperception of the effectiveness of financial regulations, perhaps coupled with a lack of understand...

  9. Ceramic microfabrication by rapid prototyping process chains

    Indian Academy of Sciences (India)

    Ceramic microfabrication by rapid prototyping process chains ... is nearly impossible, shaping has to be done by a replication step in the green, unfired state. ... This process chain combines the fast and inexpensive supply of master models by ...

  10. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie; Danquah, Agyemang; Zé licourt, Axel de; Hirt, Heribert; Colcombet, Jean

    2015-01-01

    rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests

  11. Integrating Rapid Prototyping into Graphic Communications

    Science.gov (United States)

    Xu, Renmei; Flowers, Jim

    2015-01-01

    Integrating different science, technology, engineering, and mathematics (STEM) areas can help students learn and leverage both the equipment and expertise at a single school. In comparing graphic communications classes with classes that involve rapid prototyping (RP) technologies like 3D printing, there are sufficient similarities between goals,…

  12. Rapid City Native American Population Needs Assessment.

    Science.gov (United States)

    Farrokhi, Abdollah

    1993-01-01

    Interviews with 301 Native American households in Rapid City, South Dakota, examined demographic variables and attitudes and needs in the areas of education, housing, transportation, health care, recreation, and employment. The ultimate goals for Native American people are achieving empowerment and group determination through greater cultural…

  13. High precision, rapid laser hole drilling

    Science.gov (United States)

    Chang, Jim J.; Friedman, Herbert W.; Comaskey, Brian J.

    2013-04-02

    A laser system produces a first laser beam for rapidly removing the bulk of material in an area to form a ragged hole. The laser system produces a second laser beam for accurately cleaning up the ragged hole so that the final hole has dimensions of high precision.

  14. Utilizing Rapid Prototyping for Architectural Modeling

    Science.gov (United States)

    Kirton, E. F.; Lavoie, S. D.

    2006-01-01

    This paper will discuss our approach to, success with and future direction in rapid prototyping for architectural modeling. The premise that this emerging technology has broad and exciting applications in the building design and construction industry will be supported by visual and physical evidence. This evidence will be presented in the form of…

  15. A rapidly enlarging cutaneous hemangioma in pregnancy.

    LENUS (Irish Health Repository)

    Ma'ayeh, Marwan

    2014-06-18

    This is a case of a rapidly enlarging cutaneous pedunculated tumor on a patient\\'s thumb during her pregnancy. This was excised and identified as a hemangioma. A literature search identified a possible hormonal factor in causing an accelerated growth of this tumor.

  16. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul

    2009-01-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...

  17. Rapid arc - clinical rationale and results

    International Nuclear Information System (INIS)

    Cozzi, Lucca

    2008-01-01

    The presentation will focus on the background of Intensity modulation volumetric arc therapy Rapid Arc from Varian Medical Systems aiming to highlight the technical and clinical rational also from an historical perspective to the founding pillars of fast delivery with a minimum number of arcs and a minimum number of monitor units

  18. Rapid thermal annealing of phosphorus implanted silicon

    International Nuclear Information System (INIS)

    Lee, Y.H.; Pogany, A.; Harrison, H.B.; Williams, J.S.

    1985-01-01

    Rapid thermal annealing (RTA) of phosphorus-implanted silicon has been investigated by four point probe, Van der Pauw methods and transmission electron microscopy. The results have been compared to furnace annealing. Experiments show that RTA, even at temperatures as low as 605 deg C, results in good electrical properties with little remnant damage and compares favourably with furnace annealing

  19. Utilizing Information Technology to Facilitate Rapid Acquisition

    Science.gov (United States)

    2006-06-01

    PAGES 109 14. SUBJECT TERMS Rapid Acquisition, eCommerce , eProcurement, Information Technology, Contracting, Global Information Network...Agency. 5 eCommerce and eProcurement, and possess an adequate knowledge of information technology. D. RESEARCH QUESTIONS 1. Primary Research... eCommerce , Information Technology, and eProcurement knowledge, and government and private industry reports utilizing numerous library and Internet

  20. Cognitive Predictors of Rapid Picture Naming

    Science.gov (United States)

    Decker, Scott L.; Roberts, Alycia M.; Englund, Julia A.

    2013-01-01

    Deficits in rapid automatized naming (RAN) have been found to be a sensitive cognitive marker for children with dyslexia. However, there is a lack of consensus regarding the construct validity and theoretical neuro-cognitive processes involved in RAN. Additionally, most studies investigating RAN include a narrow range of cognitive measures. The…