WorldWideScience

Sample records for factor crf system

  1. Stress and addiction: contribution of the corticotropin releasing factor (CRF system in neuroplasticity

    Directory of Open Access Journals (Sweden)

    Carolina L Haass-Koffler

    2012-09-01

    Full Text Available Corticotropin releasing factor (CRF has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs. CRF has been associated with stress-induced drug reinforcement. Extensive literature has identified CRF to play an important role in the molecular mechanisms that lead to an increase in susceptibility that precipitates relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the acute effects of drugs of abuse and is also responsible for the potentiation of drug-induced neuroplasticity evoked during the withdrawal period. We present in this review the brain regions and circuitries where CRF is expressed and may participate in stress-induced drug abuse. Finally, we attempt to evaluate the role of modulating the CRF system as a possible therapeutic strategy for treating the dysregulation of emotional behaviors that result from the acute positive reinforcement of substances of abuse as well as the negative reinforcement produced by withdrawal.

  2. The CRF system and social behavior: a review.

    Science.gov (United States)

    Hostetler, Caroline M; Ryabinin, Andrey E

    2013-01-01

    The corticotropin-releasing factor (CRF) system plays a key role in a diversity of behaviors accompanying stress, anxiety and depression. There is also substantial research on relationships between social behaviors and the CRF system in a variety of taxa including fish, birds, rodents, and primates. Some of these relationships are due to the broad role of CRF and urocortins in stress and anxiety, but these peptides also modulate social behavior specifically. For example, the social interaction (SI) test is often used to measure anxiety-like behavior. Many components of the CRF system including CRF, urocortin1, and the R1 receptor have been implicated in SI, via general effects on anxiety as well as specific effects depending on the brain region. The CRF system is also highly responsive to chronic social stressors such as social defeat and isolation. Animals exposed to these stressors display a number of anxiety- and stress-related behaviors, accompanied by changes in specific components the CRF system. Although the primary focus of CRF research on social behavior has been on the deleterious effects of social stress, there are also insights on a role for CRF and urocortins in prosocial and affiliative behaviors. The CRF system has been implicated in parental care, maternal defense, sexual behavior, and pair bonding. Species differences in the ligands and CRF receptors have been observed in vole and bird species differing in social behavior. Exogenous administration of CRF facilitates partner preference formation in monogamous male prairie voles, and these effects are dependent on both the CRF R1 and R2 receptors. These findings are particularly interesting as studies have also implicated the CRF and urocortins in social memory. With the rapid progress of social neuroscience and in understanding the complex structure of the CRF system, the next challenge is in parsing the exact contribution of individual components of this system to specific social behaviors.

  3. The CRF System and Social Behavior: A Review

    Directory of Open Access Journals (Sweden)

    Caroline M Hostetler

    2013-05-01

    Full Text Available The corticotropin-releasing factor (CRF system plays a key role in a diversity of behaviors accompanying stress, anxiety and depression. There is also substantial research on relationships between social behaviors and the CRF system in a variety of taxa including fish, birds, rodents, and primates. Some of these relationships are due to the broad role of CRF and urocortins in stress and anxiety, but these peptides also modulate social behavior specifically. For example, the social interaction (SI test is often used to measure anxiety-like behavior. Many components of the CRF system including CRF, urocortin1, and the R1 receptor have been implicated in SI, via general effects on anxiety as well as specific effects depending on the brain region. The CRF system is also highly responsive to chronic social stressors such as social defeat and isolation. Animals exposed to these stressors display a number of anxiety- and stress-related behaviors, accompanied by changes in specific components the CRF system. Although the primary focus of CRF research on social behavior has been on the deleterious effects of social stress, there are also insights on a role for CRF and urocortins in prosocial and affiliative behaviors. The CRF system has been implicated in parental care, maternal defense, sexual behavior, and pair bonding. Species differences in the ligands and CRF receptors have been observed in vole and bird species differing in social behavior. Exogenous administration of CRF facilitates partner preference formation in monogamous male prairie voles, and these effects are dependent on both the CRF R1 and R2 receptors. These findings are particularly interesting as studies have also implicated the CRF and urocortins in social memory. With the rapid progress of social neuroscience and in understanding the complex structure of the CRF system, the next challenge is in parsing the exact contribution of individual components of this system to specific social

  4. Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in Alcohol Drinking.

    Science.gov (United States)

    Schreiber, Allyson L; Gilpin, Nicholas W

    2018-01-28

    Alcohol use is pervasive in the United States. In the transition from nonhazardous drinking to hazardous drinking and alcohol use disorder, neuroadaptations occur within brain reward and brain stress systems. One brain signaling system that has received much attention in animal models of excessive alcohol drinking and alcohol dependence is corticotropin-releasing factor (CRF). The CRF system is composed of CRF, the urocortins, CRF-binding protein, and two receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge, and chronic alcohol dysregulates CRF signaling in hypothalamic and extra-hypothalamic brain regions and how this dysregulation may contribute to changes in alcohol reinforcement, excessive alcohol consumption, symptoms of negative affect during withdrawal, and alcohol relapse. In addition, it summarizes clinical work examining CRF type 1 receptor antagonists in humans and discusses why the brain CRF system is still relevant in alcohol research.

  5. Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.

    Science.gov (United States)

    Rivier, J; Gulyas, J; Kirby, D; Low, W; Perrin, M H; Kunitake, K; DiGruccio, M; Vaughan, J; Reubi, J C; Waser, B; Koerber, S C; Martinez, V; Wang, L; Taché, Y; Vale, W

    2002-10-10

    We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in

  6. Identification of corticotropin-releasing factor (CRF) target cells and effects of dexamethasone on binding in anterior pituitary using a fluorescent analog of CRF

    DEFF Research Database (Denmark)

    Schwartz, J; Billestrup, Nils; Perrin, M

    1986-01-01

    A fluorescein-conjugated bioactive analog of corticotropin-releasing factor (CRF) was synthesized and used to label cells that have high affinity CRF-binding sites. Of cultured bovine anterior pituitary cells, 6.1 +/- 0.6% were visible by fluorescence microscopy after incubation with the analog......-binding sites and suggest that binding of CRF to anterior pituitary cells is altered by glucocorticoids....

  7. The neuroanatomic complexity of the CRF and DA systems and their interface: What we still don't know.

    Science.gov (United States)

    Kelly, E A; Fudge, J L

    2018-07-01

    Corticotropin-releasing factor (CRF) is a neuropeptide that mediates the stress response. Long known to contribute to regulation of the adrenal stress response initiated in the hypothalamic-pituitary axis (HPA), a complex pattern of extrahypothalamic CRF expression is also described in rodents and primates. Cross-talk between the CRF and midbrain dopamine (DA) systems links the stress response to DA regulation. Classically CRF + cells in the extended amygdala and paraventricular nucleus (PVN) are considered the main source of this input, principally targeting the ventral tegmental area (VTA). However, the anatomic complexity of both the DA and CRF system has been increasingly elaborated in the last decade. The DA neurons are now recognized as having diverse molecular, connectional and physiologic properties, predicted by their anatomic location. At the same time, the broad distribution of CRF cells in the brain has been increasingly delineated using different species and techniques. Here, we review updated information on both CRF localization and newer conceptualizations of the DA system to reconsider the CRF-DA interface. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

    Science.gov (United States)

    Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

    2013-09-01

    Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

  9. Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors

    Science.gov (United States)

    Reyes, T. M.; Lewis, K.; Perrin, M. H.; Kunitake, K. S.; Vaughan, J.; Arias, C. A.; Hogenesch, J. B.; Gulyas, J.; Rivier, J.; Vale, W. W.; Sawchenko, P. E.

    2001-01-01

    Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)+ RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1–10 μg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation. PMID:11226328

  10. CRF1-R activation of the dynorphin/kappa opioid system in the mouse basolateral amygdala mediates anxiety-like behavior.

    Directory of Open Access Journals (Sweden)

    Michael R Bruchas

    2009-12-01

    Full Text Available Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF were triggered by CRF(1-R activation of the dynorphin/kappa opioid receptor (KOR system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM. The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI, and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF(1-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF(2-R agonist urocortin III did not affect open arm time, and mice lacking CRF(2-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF(2-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF(1-R activation may mediate anxiety and CRF(2-R may encode aversion. Using a phosphoselective antibody (KORp to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA of wildtype, but not in mice pretreated with the selective CRF(1-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was

  11. The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.

    Science.gov (United States)

    Morisot, Nadège; Contarino, Angelo

    2016-06-01

    Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and their respective wild-type mice are injected with escalating doses of morphine and cognitive function assessed by the novel object recognition (NOR) memory task throughout relatively long periods of opiate withdrawal. Early (2 days) phases of opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice. However, the duration of opiate withdrawal-induced NOR memory deficits is prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their respective wild-type mice, indicating opposite roles for the two CRF receptor subtypes. Nevertheless, following apparent recovery, exposure to an environmental stressor induces the reemergence of NOR memory deficits in long-term opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an essential role for both CRF receptor subtypes in stress vulnerability. These findings bring initial evidence of a complex physiopathological role for the CRF system in cognitive deficits and the long-lasting vulnerability induced by opiate drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor.

    Science.gov (United States)

    Lewis, K; Li, C; Perrin, M H; Blount, A; Kunitake, K; Donaldson, C; Vaughan, J; Reyes, T M; Gulyas, J; Fischer, W; Bilezikjian, L; Rivier, J; Sawchenko, P E; Vale, W W

    2001-06-19

    The corticotropin-releasing factor (CRF) family of neuropeptides includes the mammalian peptides CRF, urocortin, and urocortin II, as well as piscine urotensin I and frog sauvagine. The mammalian peptides signal through two G protein-coupled receptor types to modulate endocrine, autonomic, and behavioral responses to stress, as well as a range of peripheral (cardiovascular, gastrointestinal, and immune) activities. The three previously known ligands are differentially distributed anatomically and have distinct specificities for the two major receptor types. Here we describe the characterization of an additional CRF-related peptide, urocortin III, in the human and mouse. In searching the public human genome databases we found a partial expressed sequence tagged (EST) clone with significant sequence identity to mammalian and fish urocortin-related peptides. By using primers based on the human EST sequence, a full-length human clone was isolated from genomic DNA that encodes a protein that includes a predicted putative 38-aa peptide structurally related to other known family members. With a human probe, we then cloned the mouse ortholog from a genomic library. Human and mouse urocortin III share 90% identity in the 38-aa putative mature peptide. In the peptide coding region, both human and mouse urocortin III are 76% identical to pufferfish urocortin-related peptide and more distantly related to urocortin II, CRF, and urocortin from other mammalian species. Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin. Urocortin III is selective for type 2 CRF receptors and thus represents another potential endogenous ligand for these receptors.

  13. Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

    1985-01-01

    The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125 I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR

  14. CRF1 receptor-deficiency increases cocaine reward.

    Science.gov (United States)

    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-05-01

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF 1 receptor-deficient (CRF 1 -/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF 1 -/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF 1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF 1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF 1 -/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF 1 -/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF 1 -/- mice by exogenous corticosterone does not affect CRF 1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF 1 receptor in cocaine reward, independently of the closely related HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Fear extinction learning can be impaired or enhanced by modulation of the CRF system in the basolateral nucleus of the amygdala

    OpenAIRE

    Abiri, Dina; Douglas, Christina E.; Calakos, Katina C.; Barbayannis, Georgia; Roberts, Andrea; Bauer, Elizabeth P.

    2014-01-01

    The neuropeptide corticotropin-releasing factor (CRF) is released during periods of anxiety and modulates learning and memory formation. One region with particularly dense concentrations of CRF receptors is the basolateral nucleus of the amygdala (BLA), a critical structure for both Pavlovian fear conditioning and fear extinction. While CRF has the potential to modify amygdala-dependent learning, its effect on fear extinction has not yet been assessed. In the present study, we examined the mo...

  16. Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.

    Science.gov (United States)

    Gondré-Lewis, Marjorie C; Warnock, Kaitlin T; Wang, Hong; June, Harry L; Bell, Kimberly A; Rabe, Holger; Tiruveedhula, Veera Venkata Naga Phani Babu; Cook, James; Lüddens, Hartmut; Aurelian, Laure; June, Harry L

    2016-01-01

    Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the

  17. An update on CRF mechanisms underlying alcohol use disorders and dependence.

    Directory of Open Access Journals (Sweden)

    Isabel Marian Hartmann Quadros

    2016-10-01

    Full Text Available Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin Releasing Factor (CRF systems have been critically implied in the transition towards problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic-pituitary-adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF binding protein and Urocortins, a family of CRF-related peptides.

  18. The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent.

    Science.gov (United States)

    Bosch, Oliver J; Nair, Hemanth P; Ahern, Todd H; Neumann, Inga D; Young, Larry J

    2009-05-01

    Social relationships significantly influence physiology and behavior, including the hypothalamo-pituitary-adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-coping behaviors indicative of depressive-like behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-coping behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.

  19. Human CRF2 α and β splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

    International Nuclear Information System (INIS)

    Ardati, A.; Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J.; Valdenaire, O.

    1999-01-01

    Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF 1 and CRF 2 ). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF 2 subtype receptors, CRF 2α and CRF 2β , have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF 2β receptor. We have used radioligand binding with [ 125 I]-tyr 0 -sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [ 125 I]-tyr 0 -sauvagine binding to the hCRF 2β receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF 2α receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF 2α receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [ 125 I]-tyr 0 -sauvagine to both hCRF 2 receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF 2 α-helical CRF (9-41) oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist α-helical CRF (9-41) exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF 2 receptor isoforms. Taken together, these results indicate that the pharmacological profiles of the CRF 2 splice variants are identical. This indicates that the region of the N-terminus that varies

  20. Corticotropin-releasing factor (CRF) receptors in intermediate lobe of the pituitary: Biochemical characterization and autoradiographic localization

    International Nuclear Information System (INIS)

    Grigoriadis, D.E.; De Souza, E.B.

    1989-01-01

    CRF receptors were characterized using radioligand binding and chemical affinity cross-linking techniques and localized using autoradiographic techniques in porcine, bovine and rat pituitaries. The binding of 125I-[Tyr0]-ovine CRF (125I-oCRF) to porcine anterior and neurointermediate lobe membranes was saturable and of high affinity with comparable KD values (200-600 pM) and receptor densities (100-200 fmoles/mg protein). The pharmacological rank order of potencies for various analogs and fragments of CRF in inhibiting 125I-oCRF binding in neurointermediate lobe was characteristic of the well-established CRF receptor in anterior pituitary. Furthermore, the binding of 125I-oCRF to both anterior and neurointermediate lobes of the pituitary was guanine nucleotide-sensitive. Affinity cross-linking studies revealed that the molecular weight of the CRF binding protein in rat intermediate lobe was identical to that in rat anterior lobe (Mr = 75,000). While the CRF binding protein in the anterior lobes of porcine and bovine pituitaries had identical molecular weights to CRF receptors in rat pituitary (Mr = 75,000), the molecular weight of the CRF binding protein in porcine and bovine intermediate lobe was slightly higher (Mr = 78,000). Pituitary autoradiograms from the three species showed specific binding sites for 125I-oCRF in anterior and intermediate lobes, with none being apparent in the posterior pituitary. The identification of CRF receptors in the intermediate lobe with comparable characteristics to those previously identified in the anterior pituitary substantiate further the physiological role of CRF in regulating intermediate lobe hormone secretion

  1. Sex, social status, and CRF receptor densities in naked mole-rats.

    Science.gov (United States)

    Beery, Annaliese K; Bicks, Lucy; Mooney, Skyler J; Goodwin, Nastacia L; Holmes, Melissa M

    2016-02-01

    Naked mole-rats (Heterocephalus glaber) live in groups that are notable for their large size and caste structure, with breeding monopolized by a single female and a small number of males. Recent studies have demonstrated substantial differences between the brains of breeders and subordinates induced by changes in social standing. Corticotropin-releasing factor (CRF) receptors-which bind the hormone CRF as well as related peptides-are important regulators of stress and anxiety, and are emerging as factors affecting social behavior. We conducted autoradiographic analyses of CRF1 and CRF2 receptor binding densities in female and male naked mole-rats varying in breeding status. Both globally and in specific brain regions, CRF1 receptor densities varied with breeding status. CRF1 receptor densities were higher in subordinates across brain regions, and particularly in the piriform cortex and cortical amygdala. Sex differences were present in CRF2 receptor binding densities, as is the case in multiple vole species. CRF2 receptor densities were higher in females, both globally and in the cortical amygdala and lateral amygdalar nucleus. These results provide novel insights into the neurobiology of social hierarchy in naked mole-rats, and add to a growing body of work that links changes in the CRF system with social behavior. © 2015 Wiley Periodicals, Inc.

  2. Human CRF{sub 2} {alpha} and {beta} splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

    Energy Technology Data Exchange (ETDEWEB)

    Ardati, A. [Rhone-Poulenc Rorer, Cardiovascular Biology, NW4, 500 Arcola Road, Collegeville, PA (United States); Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J. [Central Nervous System, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland); Valdenaire, O. [Cardiovascular Research, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland)

    1999-03-14

    Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF{sub 1} and CRF{sub 2}). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF{sub 2} subtype receptors, CRF{sub 2{alpha}} and CRF{sub 2{beta}}, have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF{sub 2{beta}} receptor. We have used radioligand binding with [{sup 125}I]-tyr{sup 0}-sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [{sup 125}I]-tyr{sup 0}-sauvagine binding to the hCRF{sub 2{beta}} receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF{sub 2{alpha}} receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF{sub 2{alpha}} receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [{sup 125}I]-tyr{sup 0}-sauvagine to both hCRF{sub 2} receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF{sub 2}{alpha}-helical CRF{sub (9-41)}oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist {alpha}-helical CRF{sub (9-41)} exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF{sub 2} receptor isoforms. Taken together, these results indicate that the

  3. Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.

    Science.gov (United States)

    Qi, Xiaoli; Guzhva, Lidia; Yang, Zhihui; Febo, Marcelo; Shan, Zhiying; Wang, Kevin K W; Bruijnzeel, Adriaan W

    2016-09-01

    Smoking cessation leads to dysphoria and anxiety, which both increase the risk for relapse. This negative affective state is partly mediated by an increase in activity in brain stress systems. Recent studies indicate that prolonged viral vector-mediated overexpression of stress peptides diminishes stress sensitivity. Here we investigated whether the overexpression of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) diminishes nicotine withdrawal symptoms in rats. The effect of nicotine withdrawal on brain reward function was investigated with an intracranial self-stimulation (ICSS) procedure. Anxiety-like behavior was investigated in the elevated plus maze test and a large open field. An adeno-associated virus (AAV) pseudotype 2/5 vector was used to overexpress CRF in the lateral BNST and nicotine dependence was induced using minipumps. Administration of the nicotinic receptor antagonist mecamylamine and cessation of nicotine administration led to a dysphoria-like state, which was prevented by the overexpression of CRF in the BNST. Nicotine withdrawal also increased anxiety-like behavior in the elevated plus maze test and large open field test and slightly decreased locomotor activity in the open field. The overexpression of CRF in the BNST did not prevent the increase in anxiety-like behavior or decrease in locomotor activity. The overexpression of CRF increased CRF1 and CRF2 receptor gene expression and increased the CRF2/CRF1 receptor ratio. In conclusion, the overexpression of CRF in the BNST prevents the dysphoria-like state associated with nicotine withdrawal and increases the CRF2/CRF1 receptor ratio, which may diminish the negative effects of CRF on mood. Published by Elsevier B.V.

  4. The Effect of Short Moderate Stress on the Midbrain CRF System in a Macaque Model of Functional Hypothalamic Amenorrhea

    Science.gov (United States)

    Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

    2014-01-01

    Objective To study the effect of moderate stress on CRF components in the serotonergic midbrain region in a monkey model of FHA. Design After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days prior to euthanasia. Setting University of Pittsburgh nonhuman primate facility. Animals Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n=5), medium stress resilient (MSR, N=4) or stress sensitive (SS, n=4). Intervention 5 days of diet in a novel room with unfamiliar conspecifics. Main Outcome Measures Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of UCN1 cells; the density of UCN1 axons; the expression of CRF-R1 and CRF-R2 in the dorsal raphe nucleus. Results CRF innervation was higher in HSR than SS animals; UCN1 cell number was higher in HSR than SS animals and UCN1 axon bouton density was not different, all opposite of non-stressed animals. CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than SS animals. The relative expression of CRF-R1 and R2 was similar to non-stressed animals. Conclusions HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. PMID:23849846

  5. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L., E-mail: laorden@um.es

    2014-02-15

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

  6. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    International Nuclear Information System (INIS)

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

    2014-01-01

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence

  7. Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

    Science.gov (United States)

    Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

    2013-01-01

    Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

  8. CRF-like diuretic hormone negatively affects both feeding and reproduction in the desert locust, Schistocerca gregaria.

    Directory of Open Access Journals (Sweden)

    Pieter Van Wielendaele

    Full Text Available Diuretic hormones (DH related to the vertebrate Corticotropin Releasing Factor (CRF have been identified in diverse insect species. In the migratory locust, Locusta migratoria, the CRF-like DH (CRF/DH is localized in the same neurosecretory cells as the Ovary Maturating Parsin (OMP, a neurohormone that stimulates oocyte growth, vitellogenesis and hemolymph ecdysteroid levels in adult female locusts. In this study, we investigated whether CRF-like DH can influence feeding and reproduction in the desert locust, Schistocerca gregaria. We identified two highly similar S. gregaria CRF-like DH precursor cDNAs, each of which also encodes an OMP isoform. Alignment with other insect CRF-like DH precursors shows relatively high conservation of the CRF/DH sequence while the precursor region corresponding to OMP is not well conserved. Quantitative real-time RT-PCR revealed that the precursor transcripts mainly occur in the central nervous system and their highest expression level was observed in the brain. Injection of locust CRF/DH caused a significantly reduced food intake, while RNAi knockdown stimulated food intake. Therefore, our data indicate that CRF-like DH induces satiety. Furthermore, injection of CRF/DH in adult females retarded oocyte growth and caused lower ecdysteroid titers in hemolymph and ovaries, while RNAi knockdown resulted in opposite effects. The observed effects of CRF/DH may be part of a wider repertoire of neurohormonal activities, constituting an integrating control system that affects food intake and excretion, as well as anabolic processes like oocyte growth and ecdysteroidogenesis, following a meal. Our discussion about the functional relationship between CRF/DH and OMP led to the hypothesis that OMP may possibly act as a monitoring peptide that can elicit negative feedback effects.

  9. The Effect of Citalopram on Midbrain CRF Receptors 1 and 2 in a Primate Model of Stress-Induced Amenorrhea

    Science.gov (United States)

    Senashova, Olga; Reddy, Arubala P.; Cameron, Judy L.; Bethea, Cynthia L.

    2012-01-01

    We have demonstrated marked differences in the neurobiology of the serotonin system between stress-sensitive (SS) and stress-resilient (SR) cynomolgus macaques characterized in a model of stress-induced amenorrhea, also called functional hypothalamic amenorrhea (FHA). Dysfunction of the serotonin system in SS monkeys suggested that administration of a selective serotonin reuptake inhibitor (SSRI) might correct FHA. This study examines the effect of escitalopram (CIT) administration to SS and SR monkeys on corticotrophin-releasing factor (CRF) receptor 1 (CRF-R1) and CRF receptor 2 (CRF-R2) gene expression in the serotonin cell body region of the midbrain dorsal raphe. CRF-R1 was not significantly different between groups. There was a significant effect of treatment and a significant interaction between treatment and stress sensitivity on the average CRF-R2-positive pixel area (P < .004 and P < .006, respectively) and on the average number of CRF-R2-positive cells (P < .023 and P < .025, respectively). CIT significantly increased CRF-R2-positive pixel area and cell number in the SS group (pixel area P < .001; cell number P < .01; Bonferoni) but not in the SR group. In summary, CIT administration tended to decrease CRF-R1, but the small animal number precluded significance. CIT administration significantly increased CRF-R2 only in SS animals. These data suggest that the administration of CIT reduces anxiogenic components and increases anxiolytic components of the CRF system in the midbrain serotonin network, which in turn leads to improved ovarian function. Moreover, these data raise the possibility that SSRIs may be effective in the treatment of stress-induced infertility. PMID:22412189

  10. The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response

    Science.gov (United States)

    Dedic, Nina; Chen, Alon; Deussing, Jan M.

    2018-01-01

    Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and conse-quently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacologi-cal studies to genetic mouse models and virus-mediated manipulations. Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, includ-ing anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiol-ogy and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions. Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mecha-nisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely un-derstood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of

  11. Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole-rats and solitary Cape mole-rats.

    Science.gov (United States)

    Coen, Clive W; Kalamatianos, Theodosis; Oosthuizen, Maria K; Poorun, Ravi; Faulkes, Christopher G; Bennett, Nigel C

    2015-11-01

    Various aspects of social behavior are influenced by the highly conserved corticotrophin-releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF1 and CRF2 , and two of their ligands, CRF and urocortin 3, respectively, in African mole-rat species with diametrically opposed social behavior. Naked mole-rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole-rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF1 binding in naked mole-rats exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole-rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF2 binding, the sites with a greater level in naked mole-rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole-rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF1 binding in the nucleus accumbens of Cape mole-rats reflects their lack of affiliative behavior. © 2015 Wiley Periodicals, Inc.

  12. Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and ischaemic conditions.

    Science.gov (United States)

    De Michele, Manuela; Touzani, Omar; Foster, Alan C; Fieschi, Cesare; Sette, Giuliano; McCulloch, James

    2005-09-01

    The expression of corticotrophin-releasing factor (CRF) receptors in cerebral arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF). In the present study, the effects of CRF, CRF-like peptides and the CRF broad spectrum antagonist DPhe-CRF on CBF have been investigated under normal physiologic conditions and in the margins of focal ischaemic insult. The experiments were carried out in anaesthetised and ventilated rats. Changes in CBF after subarachnoid microapplication of CRF and related peptides were assessed with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were injected approximately 60 minutes after permanent middle cerebral artery occlusion (MCAo). Microapplication of CRF and related peptides in normal rats into the subarachnoid space produced sustained concentration-dependent increases in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not alter CBF itself. A second microapplication of CRF 30 min after the first failed to produce increases in CBF in normal animals. Microapplication of CRF in the subarachnoid space overlying the ischaemic cortex effected minor increases in CBF whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF peptidergic system increases CBF in the rat. Repeated activation of CRF receptors results in tachyphylaxis of the vasodilator response. CRF vasodilator response is still present after MCAo in the ischaemic penumbra, suggesting that the CRF peptidergic system may modulate CBF in ischaemic stroke.

  13. CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice.

    Directory of Open Access Journals (Sweden)

    Lixin Wang

    2011-02-01

    Full Text Available Corticotropin-releasing factor (CRF signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

  14. Recovery of stress-impaired social behavior by an antagonist of the CRF binding protein, CRF6-33, in the bed nucleus of the stria terminalis of male rats.

    Science.gov (United States)

    Vasconcelos, Mailton; Stein, Dirson J; Albrechet-Souza, Lucas; Miczek, Klaus A; de Almeida, Rosa Maria M

    2018-01-09

    Social stress is recognized to promote the development of neuropsychiatric and mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide activated by social stress, and it contributes to neural and behavioral adaptations, as indicated by impaired social interactions and anhedonic effects. Few studies have focused on the role of the CRF binding protein (CRFBP), a component of the CRF system, and its activity in the bed nucleus of stria terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In this study, animals' preference for sweet solutions was examined as an index of stress-induced anhedonic responses in Wistar rats subjected to four brief intermittent episodes of social defeat. Next, social approach was assessed after local infusions of the CRFBP antagonist, CRF fragment 6-33 (CRF 6-33 ) into the BNST. The experience of brief episodes of social defeat impaired social approach behaviors in male rats. However, intra-BNST CRF 6-33 infusions restored social approach in stressed animals to the levels of non-stressed rats. CRF 6-33 acted selectively on social interaction and did not alter general exploration in nether stressed nor non-stressed rats. These findings suggest that BNST CRFBP is involved in the modulation of anxiety-like responses induced by social stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Inhibition of the CRF1 receptor influences the activity of antidepressant drugs in the forced swim test in rats.

    Science.gov (United States)

    Wróbel, Andrzej; Serefko, Anna; Szopa, Aleksandra; Rojek, Karol; Poleszak, Ewa; Skalicka-Woźniak, Krystyna; Dudka, Jarosław

    2017-08-01

    Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of the central corticotropin-releasing factor (CRF) system are factors in the pathogenesis of depression. Though several antagonists of the CRF 1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between CRF 1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of SN003, a CRF 1 receptor blocker, on the activity of imipramine and fluoxetine in the forced swim test (FST) in rats which presented some signs of depression. The experiments were carried out on female Wistar rats subjected to 14-day subcutaneous corticosterone (CORT) administration (20 mg/kg/day). The antidepressant-like effect was determined by the FST and the CRF levels in the hypothalamus, amygdala, and peripheral blood were measured by a high-sensitivity immunoenzymatic test. SN003 (0.5 mg/kg) potentiated the antidepressant-like effect of imipramine (15 mg/kg) and fluoxetine (7.5 mg/kg). Moreover, the co-administration of the tested agents abolished CORT-induced increase in CRF levels in the examined biological material more profoundly than monotherapy. Our present findings give further evidence that the blockage of CRF action may be useful in the treatment of mood disorders. The concurrent use of well-known antidepressants with CRF 1 receptor antagonists could be beneficial in terms of safety, since it requires lower doses of the applied agents.

  16. Grin1 receptor deletion within CRF neurons enhances fear memory.

    Directory of Open Access Journals (Sweden)

    Georgette Gafford

    Full Text Available Corticotropin releasing factor (CRF dysregulation is implicated in mood and anxiety disorders such as posttraumatic stress disorder (PTSD. CRF is expressed in areas engaged in fear and anxiety processing including the central amygdala (CeA. Complicating our ability to study the contribution of CRF-containing neurons to fear and anxiety behavior is the wide variety of cell types in which CRF is expressed. To manipulate specific subpopulations of CRF containing neurons, our lab has developed a mouse with a Cre recombinase gene driven by a CRF promoter (CRFp3.0Cre (Martin et al., 2010. In these studies, mice that have the gene that encodes NR1 (Grin1 flanked by loxP sites (floxed were crossed with our previously developed CRFp3.0Cre mouse to selectively disrupt Grin1 within CRF containing neurons (Cre+/fGrin1+. We find that disruption of Grin1 in CRF neurons did not affect baseline levels of anxiety, locomotion, pain sensitivity or exploration of a novel object. However, baseline expression of Grin1 was decreased in Cre+/fGrin1+ mice as measured by RTPCR. Cre+/fGrin1+ mice showed enhanced auditory fear acquisition and retention without showing any significant effect on fear extinction. We measured Gria1, the gene that encodes AMPAR1 and the CREB activator Creb1 in the amygdala of Cre+/fGrin1+ mice after fear conditioning. Both Gria1 and Creb1 were enhanced in the amygdala after training. To determine if the Grin1-expressing CRF neurons within the CeA are responsible for the enhancement of fear memory in adults, we infused a lentivirus with Cre driven by a CRF promoter (LV pCRF-Cre/fGrin1+ into the CeA of floxed Grin1 mice. Cre driven deletion of Grin1 specifically within CRF expressing cells in the CeA also resulted in enhanced fear memory acquisition and retention. Altogether, these findings suggest that selective disruption of Grin1 within CeA CRF neurons strongly enhances fear memory.

  17. A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats.

    Science.gov (United States)

    Sanford, Christina A; Soden, Marta E; Baird, Madison A; Miller, Samara M; Schulkin, Jay; Palmiter, Richard D; Clark, Michael; Zweifel, Larry S

    2017-01-04

    Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Corticotropin-releasing Factor in the Rat Dorsal Raphe Nucleus Promotes Different Forms of Behavioral Flexibility Depending on Social Stress History.

    Science.gov (United States)

    Snyder, Kevin P; Hill-Smith, Tiffany E; Lucki, Irwin; Valentino, Rita J

    2015-10-01

    The stress-related neuropeptide, corticotropin-releasing factor (CRF) regulates the dorsal raphe nucleus-serotonin (DRN-5-HT) system during stress and this may underlie affective and cognitive dysfunctions that characterize stress-related psychiatric disorders. CRF acts on both CRF1 and CRF2 receptor subtypes in the DRN that exert opposing inhibitory and excitatory effects on DRN-5-HT neuronal activity and 5-HT forebrain release, respectively. The current study first assessed the cognitive effects of intra-DRN microinfusion of CRF or the selective CRF2 agonist, urocortin II in stress-naive rats on performance of an operant strategy set-shifting task that is mediated by the medial prefrontal cortex (mPFC). CRF (30 ng) facilitated strategy set-shifting performance, whereas higher doses of CRF and urocortin II that would interact with CRF2 were without effect, consistent with a CRF1-mediated action. This dose decreased 5-HT extracellular levels in the mPFC, further supporting a role for CRF1. The effects of CRF were then assessed in rats exposed to repeated social stress using the resident-intruder model. Repeated social stress shifted the CRF effect from facilitation of strategy set shifting to facilitation of reversal learning and this was most prominent in a subpopulation of rats that resist defeat. Notably, in this subpopulation of rats 5-HT neuronal responses to CRF have been demonstrated to shift from CRF1-mediated inhibition to CRF2-mediated excitation. Because 5-HT facilitates reversal learning, the present results suggest that stress-induced changes in the cellular effects of CRF in the DRN translate to changes in cognitive effects of CRF. Together, the results underscore the potential for stress history to shift cognitive processing through changes in CRF neurotransmission in the DRN and the association of this effect with coping strategy.

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

    Science.gov (United States)

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

    2016-09-15

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

  20. Corticotropin-releasing factor (CRF) in stress and disease: A review of literature and treatment perspectives with special emphasis on psychiatric disorders

    DEFF Research Database (Denmark)

    Krohg, K.; Hageman, I.; Jorgensen, M.B.

    2008-01-01

    The CRF family of neuropeptides and receptors is involved in a variety of stress responses, in the regulation of appetite, metabolic and inflammatory processes as well as intestinal movements. From a primarily psychiatric perspective, the present paper reviews the literature on its anatomy...

  1. Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

    Directory of Open Access Journals (Sweden)

    Zhiguo Nie

    2009-01-01

    Full Text Available Corticotropin-releasing factor (CRF is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs in CeA neurons from wild-type (WT and CRF2 knockout (KO mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2 KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63 blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting

  2. Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

    Science.gov (United States)

    Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

    2018-01-04

    Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  3. Synthesis and evaluation of radioiodinated NPC 22009, a putative CRF receptor antagonist

    International Nuclear Information System (INIS)

    Balasubramanian, V.; Hiner, R.N.; Mavunkel, B.J.; Elliott, R.L.; Abreu, M.E.

    1992-01-01

    Several studies have suggested that corticotropin-releasing factor (CRF) plays a role in stress-related disorders such as anxiety, depression, anorexia nervosa and stress-induced immune suppression. Hence CRF antagonists have potential therapeutic utility. Recently the authors discovered that pyrazolones such as NPC 22009 and the corresponding disulfide behave as CRF antagonists in vitro with micromolar potency. To probe the nature of this CRF antagonism they developed a convenient synthesis of radioiodinated NPC 22009. Details of the synthesis and preliminary pharmacological studies are presented

  4. Radioimmunoassay for GRF and CRF in humans

    International Nuclear Information System (INIS)

    Stalla, G.K.; Losa, M.; Kaliebe, T.; Stalla, J.; Schopohl, J.; Muller, O.A.; Von Werder, K.

    1987-01-01

    In 1981 the structure of ovine CRF was established. One year later others isolated a 44 amino acid peptide with GH releasing activity from a pancreatic islet cell carcinoma of an acromegalic patient (hp GRF/sup 1-44/). In 1983 the gene of human CRF was cloned and the amino acid sequence of hCRF could be elucidated. It differs in 7 amino acids from oCRF. Many investigators demonstrated the biological activity of these peptides in vitro and in vivo. The aim of the authors study was to establish radioimmunoassays for GRF and hCRF with the synthetic derivates, measure endogenous GFR and CRF and circulating GRF- and CRF-levels after intravenous injection and calculate metabolic clearance rate and half-time of disappearance from serum for both releasing hormones

  5. Dominance of HIV-1 subtype CRF01_AE in sexually acquired cases leads to a new epidemic in Yunnan province of China.

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2006-11-01

    Full Text Available Dating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1 infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized.Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 321 patients representing Yunnan's 16 prefectures from four risk groups, 11 ethnic populations, and ten occupations. We identified three major circulating subtypes: C/CRF07_BC/CRF08_BC (53%, CRF01_AE (40.5%, and B (6.5% by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors, 90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08_BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes.This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development.

  6. The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

    Directory of Open Access Journals (Sweden)

    Stathopoulos Efstathios N

    2010-09-01

    Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this

  7. Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

    Directory of Open Access Journals (Sweden)

    V. S. Kulkarni

    2012-04-01

    Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

  8. Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

    Directory of Open Access Journals (Sweden)

    V. S. Kulkarni

    2011-09-01

    Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

  9. The Effect of Peripheral CRF Peptide and Water Avoidance Stress on Colonic and Gastric Transit in Guinea Pigs.

    Science.gov (United States)

    Hussain, Zahid; Kim, Hae Won; Huh, Cheal Wung; Lee, Young Ju; Park, Hyojin

    2017-07-01

    Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) diseases; however, there is frequent overlap between FD and IBS patients. Emerging evidence links the activation of corticotropin releasing factor (CRF) receptors with stress-related alterations of gastric and colonic motor function. Therefore, we investigated the effect of peripheral CRF peptide and water avoidance stress (WAS) on upper and lower GI transit in guinea pigs. Dosages 1, 3, and 10 μg/kg of CRF were injected intraperitoneally (IP) in fasted guinea pigs 30 minutes prior to the intragastric administration of charcoal mix to measure upper GI transit. Colonic transits in non-fasted guinea pigs were assessed by fecal pellet output assay after above IP CRF doses. Blockade of CRF receptors by Astressin, and its effect on GI transit was also analyzed. Guinea pigs were subjected to WAS to measure gastrocolonic transit in different sets of experiments. Dose 10 μg/kg of CRF significantly inhibited upper GI transit. In contrast, there was dose dependent acceleration of the colonic transit. Remarkably, pretreatment of astressin significantly reverses the effect of CRF peptide on GI transit. WAS significantly increase colonic transit, but failed to accelerate upper GI transit. Peripheral CRF peptide significantly suppressed upper GI transit and accelerated colon transit, while central CRF involved WAS stimulated only colonic transit. Therefore, peripheral CRF could be utilized to establish the animal model of overlap syndrome. © Copyright: Yonsei University College of Medicine 2017.

  10. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  11. Forebrain CRF1 Modulates Early-Life Stress-Programmed Cognitive Deficits

    Science.gov (United States)

    Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor; Wolf, Miriam; Liebl, Claudia; Scharf, Sebastian H.; Rice, Courtney J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Stewart, Michael G.; Müller, Marianne B.; Schmidt, Mathias V.

    2012-01-01

    Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF1), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF1 knock-out (CRF1-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF1 in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF1 signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity. PMID:21940453

  12. Contribution of amygdala CRF neurons to chronic pain.

    Science.gov (United States)

    Andreoli, Matthew; Marketkar, Tanvi; Dimitrov, Eugene

    2017-12-01

    We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over

  13. Involvement of CRF2 signaling in enterocyte differentiation.

    Science.gov (United States)

    Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Powell, Rebecca; Buisson, Alain; Bonaz, Bruno; Jacquier-Sarlin, Muriel

    2017-07-28

    To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation. For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CRF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CRF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TRITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mRNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor krüppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by RT-PCR and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric method. CRF2 protein is preferentially expressed in undifferentiated epithelial cells from

  14. Water-avoidance stress enhances gastric contractions in freely moving conscious rats: role of peripheral CRF receptors.

    Science.gov (United States)

    Nozu, Tsukasa; Kumei, Shima; Takakusaki, Kaoru; Okumura, Toshikatsu

    2014-05-01

    Stress alters gastrointestinal motility through central and peripheral corticotropin-releasing factor (CRF) pathways. Accumulating evidence has demonstrated that peripheral CRF is deeply involved in the regulation of gastric motility, and enhances gastric contractions through CRF receptor type 1 (CRF1) and delays gastric emptying (GE) through CRF receptor type 2 (CRF2). Since little is known whether water-avoidance stress (WAS) alters gastric motility, the present study tried to clarify this question and the involvement of peripheral CRF receptor subtypes in the mechanisms. We recorded intraluminal gastric pressure waves using a perfused manometric method. The rats were anesthetized and the manometric catheter was inserted into the stomach 4-6 days before the experiments. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after initiation of WAS in nonfasted conscious rats. Solid GE for 1 h was also measured. WAS significantly increased gastric contractions. Intraperitoneal (ip) administration of astressin (100 μg/kg, 5 min prior to stress), a nonselective CRF antagonist, blocked the response to WAS. On the other hand, pretreatment (5 min prior to stress) with neither astressin2-B (200 μg/kg, ip), a selective CRF2 antagonist, nor urocortin 2 (30 μg/kg, ip), a selective CRF2 agonist, modified the response to WAS. These drugs did not alter the basal MI. WAS did not change GE. WAS may activate peripheral CRF1 but not CRF2 signaling and stimulates gastric contractions without altering GE.

  15. Repeated restraint stress lowers the threshold for response to third ventricle CRF administration.

    Science.gov (United States)

    Harris, Ruth B S

    2017-03-01

    Rats and mice exposed to repeated stress or a single severe stress exhibit a sustained increase in energetic, endocrine, and behavioral response to subsequent novel mild stress. This study tested whether the hyper-responsiveness was due to a lowered threshold of response to corticotropin releasing factor (CRF) or an exaggerated response to a standard dose of CRF. Male Sprague-Dawley rats were subjected to 3h of restraint on each of 3 consecutive days (RRS) or were non-restrained controls. RRS caused a temporary hypophagia but a sustained reduction in body weight. Eight days after the end of restraint, rats received increasing third ventricle doses of CRF (0-3.0μg). The lowest dose of CRF (0.25μg) increased corticosterone release in RRS, but not control rats. Higher doses caused the same stimulation of corticosterone in the two groups of rats. Fifteen days after the end of restraint, rats were food deprived during the light period and received increasing third ventricle doses of CRF at the start of the dark period. The lowest dose of CRF inhibited food intake during the first hour following infusion in RRS, but not control rats. All other doses of CRF inhibited food intake to the same degree in both RRS and control rats. The lowered threshold of response to central CRF is consistent with the chronic hyper-responsiveness to CRF and mild stress in RRS rats during the post-restraint period. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Molecular epidemiological study of HIV-1 CRF01_AE transmission in Hong Kong.

    Science.gov (United States)

    Chen, J H K; Wong, K H; Li, P; Chan, K C; Lee, M P; Lam, H Y; Cheng, V C C; Yuen, K Y; Yam, W C

    2009-08-15

    The objective of this study was to investigate the transmission history of the HIV-1 CRF01_AE epidemics in Hong Kong between 1994 and 2007. A total of 465 HIV-1 CRF01_AE pol sequences were derived from an in-house or a commercial HIV-1 genotyping system. Phylogenies of CRF01_AE sequences were analyzed by the Bayesian coalescent method. CRF01_AE patient population included 363 males (78.1%) and 102 females (21.9%), whereas 65% (314 of 465) were local Chinese. Major transmission routes were heterosexual contact (63%), followed by intravenous drug use (IDU) (19%) and men having sex with men (MSM) (17%). From phylogenetic analysis, local CRF01_AE strains were from multiple origins with 3 separate transmission clusters identified. Cluster 1 consisted mainly of Chinese male IDUs and heterosexuals. Clusters 2 and 3 included mainly local Chinese MSM and non-Chinese Asian IDUs, respectively. Chinese reference isolates available from China (Fujian, Guangxi, or Liaoning) were clonally related to our transmission clusters, demonstrating the epidemiological linkage of CRF01_AE infections between Hong Kong and China. The 3 individual local transmission clusters were estimated to have initiated since late 1980s and late 1990s, causing subsequent epidemics in the early 2000s. This is the first comprehensive molecular epidemiological study of HIV-1 CRF01_AE in Hong Kong. It revealed that MSM contact is becoming a major route of local CRF01_AE transmission in Hong Kong. Epidemiological linkage of CRF01_AE between Hong Kong and China observed in this study indicates the importance of regular molecular epidemiological surveillance for the HIV-1 epidemic in our region.

  17. Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

    Science.gov (United States)

    Giardino, William J; Mark, Gregory P; Stenzel-Poore, Mary P; Ryabinin, Andrey E

    2012-02-01

    Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5-10 mg/kg). While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction.

  18. Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

    Science.gov (United States)

    Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

    2015-01-01

    The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

  19. Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats.

    Science.gov (United States)

    Watanabe, Mari A; Kucenas, Sarah; Bowman, Tamara A; Ruhlman, Melissa; Knuepfer, Mark M

    2010-01-14

    Stress or cocaine evokes either a large increase in systemic vascular resistance (SVR) or a smaller increase in SVR accompanied by an increase in cardiac output (designated vascular and mixed responders, respectively) in Sprague-Dawley rats. We hypothesized that the central nucleus of the amygdala (CeA) mediates this variability. Conscious, freely-moving rats, instrumented for measurement of arterial pressure and cardiac output and for drug delivery into the CeA, were given cocaine (5 mg/kg, iv, 4-6 times) and characterized as vascular (n=15) or mixed responders (n=10). Subsequently, we administered cocaine after bilateral microinjections (100 nl) of saline or selective agents in the CeA. Muscimol (80 pmol), a GABA(A) agonist, or losartan (43.4 pmol), an AT(1) receptor antagonist, attenuated the cocaine-induced increase in SVR in vascular responders, selectively, such that vascular responders were no longer different from mixed responders. The corticotropin releasing factor (CRF) antagonist, alpha-helical CRF(9-41) (15.7 pmol), abolished the difference between cardiac output and SVR in mixed and vascular responders. We conclude that greater increases in SVR observed in vascular responders are dependent on AT(1) receptor activation and, to a lesser extent on CRF receptors. Therefore, AT(1) and CRF receptors in the CeA contribute to hemodynamic response variability to intravenous cocaine.

  20. Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

    Science.gov (United States)

    Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-10-05

    A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Effects of fluoxetine on CRF and CRF1 expression in rats exposed to the learned helplessness paradigm.

    Science.gov (United States)

    Fernández Macedo, Georgina Valeria; Cladouchos, María Laura; Sifonios, Laura; Cassanelli, Pablo Martín; Wikinski, Silvia

    2013-02-01

    Stress is a common antecedent reported by people suffering major depression. In these patients, extrahypothalamic brain areas, like the hippocampus and basolateral amygdala (BLA), have been found to be affected. The BLA synthesizes CRF, a mediator of the stress response, and projects to hippocampus. The main hippocampal target for this peptide is the CRF subtype 1 receptor (CRF1). Evidence points to a relationship between dysregulation of CRF/CRF1 extrahypothalamic signaling and depression. Because selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for depression, we investigated the effect of chronic treatment with the SSRI fluoxetine on long-term changes in CRF/CRF1 signaling in animals showing a depressive-like behavior. Male Wistar rats were exposed to the learned helplessness paradigm (LH). After evaluation of behavioral impairment, the animals were treated with fluoxetine (10 mg/kg i.p.) or saline for 21 days. We measured BLA CRF expression with RT-PCR and CRF1 expression in CA3 and the dentate gyrus of the hippocampus with in situ hybridization. We also studied the activation of one of CRF1's major intracellular signaling targets, the extracellular signal-related kinases 1 and 2 (ERK1/2) in CA3. In saline-treated LH animals, CRF expression in the BLA increased, while hippocampal CRF1 expression and ERK1/2 activation decreased. Treatment with fluoxetine reversed the changes in CRF and CRF1 expressions, but not in ERK1/2 activation. In animals exposed to the learned helplessness paradigm, there are long-term changes in CRF and CRF1 expression that are restored with a behaviorally effective antidepressant treatment.

  2. CRF2 signaling is a novel regulator of cellular adhesion and migration in colorectal cancer cells.

    Science.gov (United States)

    Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Lainé, Michèle; Cristina, Nadine; Vachez, Yvan; Scoazec, Jean-Yves; Bonaz, Bruno; Jacquier-Sarlin, Muriel

    2013-01-01

    Stress has been proposed to be a tumor promoting factor through the secretion of specific neuromediators, such as Urocortin2 and 3 (Ucn2/3), however its role in colorectal cancer (CRC) remains elusive. We observed that Ucn2/3 and their receptor the Corticotropin Releasing Factor receptor 2 (CRF2) were up-regulated in high grade and poorly differentiated CRC. This suggests a role for CRF2 in the loss of cellular organization and tumor progression. Using HT-29 and SW620 cells, two CRC cell lines differing in their abilities to perform cell-cell contacts, we found that CRF2 signals through Src/ERK pathway to induce the alteration of cell-cell junctions and the shuttle of p120ctn and Kaiso in the nucleus. In HT-29 cells, this signaling pathway also leads to the remodeling of cell adhesion by i) the phosphorylation of Focal Adhesion Kinase and ii) a modification of actin cytoskeleton and focal adhesion complexes. These events stimulate cell migration and invasion. In conclusion, our findings indicate that CRF2 signaling controls cellular organization and may promote metastatic potential of human CRC cells through an epithelial-mesenchymal transition like process. This contributes to the comprehension of the tumor-promoting effects of stress molecules and designates Ucn2/3-CRF2 tandem as a target to prevent CRC progression and aggressiveness.

  3. Spatio-Temporal History of HIV-1 CRF35_AD in Afghanistan and Iran.

    Science.gov (United States)

    Eybpoosh, Sana; Bahrampour, Abbas; Karamouzian, Mohammad; Azadmanesh, Kayhan; Jahanbakhsh, Fatemeh; Mostafavi, Ehsan; Zolala, Farzaneh; Haghdoost, Ali Akbar

    2016-01-01

    HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug

  4. Activity-based anorexia activates CRF immunoreactive neurons in female rats.

    Science.gov (United States)

    Scharner, Sophie; Friedrich, Tiemo; Goebel-Stengel, Miriam; Kobelt, Peter; Rose, Matthias; Stengel, Andreas

    2018-05-01

    Activity-based anorexia (ABA) is a well-established animal model mimicking the eating disorder anorexia nervosa (AN). Since the pathophysiology of AN is yet poorly understood and specific drug treatments are lacking so far, animal models might be useful to further understand this disease. ABA consists of time-restricted access to food for 1.5 h/day and the possibility to exercise in a running wheel for 24 h/day. This combination leads to robust body weight loss as observed in AN. Here, we investigated the activation of brain corticotropin-releasing factor (CRF) neurons, a transmitter involved in the response to stress, emotional processes and also food intake. After development of ABA, rat brains were processed for c-Fos and CRF double immunohistochemistry. ABA increased the number of c-Fos/CRF double labeled neurons in the paraventricular nucleus (PVN) and the dorsomedial hypothalamic nucleus (DMH) compared to the ad libitum (AL, ad libitum fed, no running wheel) and activity (AC, ad libitum fed, running wheel, p  0.05) group. Also the number of CRF neurons was increased in the DMH of ABA rats compared to AL and AC (p  0.05). Taken together, brain CRF activated under conditions of ABA might play a role in the development and maintenance of this animal model and possibly also in human AN. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Peripheral a-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats

    NARCIS (Netherlands)

    van den Wijngaard, R. M.; Stanisor, O. I.; van Diest, S. A.; Welting, O.; Wouters, M. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2012-01-01

    Background Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of

  6. Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the beta-adrenoceptor-cAMP pathway: dependence on glucocorticoid receptor activation.

    Science.gov (United States)

    Roozendaal, Benno; Schelling, Gustav; McGaugh, James L

    2008-06-25

    Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the beta-adrenoceptor-cAMP system in the BLA. In a first experiment, male Sprague Dawley rats received bilateral infusions of the CRF-binding protein ligand inhibitor CRF(6-33) into the BLA either alone or together with the CRF receptor antagonist alpha-helical CRF(9-41) immediately after inhibitory avoidance training. CRF(6-33) induced dose-dependent enhancement of 48 h retention latencies, which was blocked by coadministration of alpha-helical CRF(9-41), suggesting that CRF(6-33) enhances memory consolidation by displacing CRF from its binding protein, thereby increasing "free" endogenous CRF concentrations. In a second experiment, intra-BLA infusions of atenolol (beta-adrenoceptor antagonist) and Rp-cAMPS (cAMP inhibitor), but not prazosin (alpha(1)-adrenoceptor antagonist), blocked CRF(6-33)-induced retention enhancement. In a third experiment, the CRF receptor antagonist alpha-helical CRF(9-41) administered into the BLA immediately after training attenuated the dose-response effects of concurrent intra-BLA infusions of clenbuterol (beta-adrenoceptor agonist). In contrast, alpha-helical CRF(9-41) did not alter retention enhancement induced by posttraining intra-BLA infusions of either cirazoline (alpha(1)-adrenoceptor agonist) or 8-br-cAMP (cAMP analog). These findings suggest that CRF facilitates the memory-modulatory effects of noradrenergic stimulation in the BLA via an interaction with the beta-adrenoceptor-cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site. Moreover, consistent with evidence that glucocorticoids enhance memory consolidation via a similar interaction with the

  7. Functional Impact of Corticotropin-Releasing Factor Exposure on Tau Phosphorylation and Axon Transport.

    Directory of Open Access Journals (Sweden)

    Michelle H Le

    Full Text Available Stress exposure or increased levels of corticotropin-releasing factor (CRF induce hippocampal tau phosphorylation (tau-P in rodent models, a process that is dependent on the type-1 CRF receptor (CRFR1. Although these preclinical studies on stress-induced tau-P provide mechanistic insight for epidemiological work that identifies stress as a risk factor for Alzheimer's disease (AD, the actual impact of stress-induced tau-P on neuronal function remains unclear. To determine the functional consequences of stress-induced tau-P, we developed a novel mouse neuronal cell culture system to explore the impact of acute (0.5hr and chronic (2hr CRF treatment on tau-P and integral cell processes such as axon transport. Consistent with in vivo reports, we found that chronic CRF treatment increased tau-P levels and caused globular accumulations of phosphorylated tau in dendritic and axonal processes. Furthermore, while both acute and chronic CRF treatment led to significant reduction in CREB activation and axon transport of brain-derived neurotrophic factor (BDNF, this was not the case with mitochondrial transport. Acute CRF treatment caused increased mitochondrial velocity and distance traveled in neurons, while chronic CRF treatment modestly decreased mitochondrial velocity and greatly increased distance traveled. These results suggest that transport of cellular energetics may take priority over growth factors during stress. Tau-P was required for these changes, as co-treatment of CRF with a GSK kinase inhibitor prevented CRF-induced tau-P and all axon transport changes. Collectively, our results provide mechanistic insight into the consequences of stress peptide-induced tau-P and provide an explanation for how chronic stress via CRF may lead to neuronal vulnerability in AD.

  8. Sex differences between CRF1 receptor deficient mice following naloxone-precipitated morphine withdrawal in a conditioned place aversion paradigm: implication of HPA axis.

    Directory of Open Access Journals (Sweden)

    Juan-Antonio García-Carmona

    Full Text Available Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R and the different response of male and female mice in the expression and extinction of the aversive memory.We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10-60 mg/kg. Negative state associated with naloxone (1 mg/kg s.c.-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA paradigm. No sex differences for CPA expression were found in wild-type (n = 29 or CRF1R knockout (KO mice (n = 29. However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH levels observed in wild-type (n = 11 mice after CPA expression, were attenuated in CRF1R KO mice (n = 10. In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

  9. The role of non-CRF inhibition in contour detection

    NARCIS (Netherlands)

    Grigorescu, C.; Petkov, N.; Westenberg, M.A.

    2003-01-01

    We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve the performance of contour detectors. Non-CRF inhibition is exhibited by 80% of the orientation selective neurons in the primary visual cortex of macaque monkeys and has been

  10. Detecting New Words from Chinese Text Using Latent Semi-CRF Models

    Science.gov (United States)

    Sun, Xiao; Huang, Degen; Ren, Fuji

    Chinese new words and their part-of-speech (POS) are particularly problematic in Chinese natural language processing. With the fast development of internet and information technology, it is impossible to get a complete system dictionary for Chinese natural language processing, as new words out of the basic system dictionary are always being created. A latent semi-CRF model, which combines the strengths of LDCRF (Latent-Dynamic Conditional Random Field) and semi-CRF, is proposed to detect the new words together with their POS synchronously regardless of the types of the new words from the Chinese text without being pre-segmented. Unlike the original semi-CRF, the LDCRF is applied to generate the candidate entities for training and testing the latent semi-CRF, which accelerates the training speed and decreases the computation cost. The complexity of the latent semi-CRF could be further adjusted by tuning the number of hidden variables in LDCRF and the number of the candidate entities from the Nbest outputs of the LDCRF. A new-words-generating framework is proposed for model training and testing, under which the definitions and distributions of the new words conform to the ones existing in real text. Specific features called “Global Fragment Information” for new word detection and POS tagging are adopted in the model training and testing. The experimental results show that the proposed method is capable of detecting even low frequency new words together with their POS tags. The proposed model is found to be performing competitively with the state-of-the-art models presented.

  11. Chronic renal failure (CRF in children in Jugoslavia

    Directory of Open Access Journals (Sweden)

    Peco-Antić Amira

    2003-01-01

    Full Text Available The aim of this study was to analyse the demographic variables of chronic non-terminal (CRF and terminal (TRF renal failure patients (pts younger than 19 years treated in Serbia in June 2001. The prevalence of CRF pts was registered as 4,7 per million total population (pmtp or 14,1 per million child population (pmcp while corresponding values for TRF pts were 4,5 pmtp or 13,5 pmcp. The incidence of TRF pts during the period Jan.2000-Jan.2002 was 4,35 pmcp. Boys dominated only among CRF pts (34:14; 60,4% beeing between the ages of 6 and 19 yrs while at the time of diagnosis of HBI, 33,3 % of boys were yanger than 2 yrs.The causes of CRF were: reflux nephropathy 58,3%, congenital kidney disease 16,7%, familial/hereditary 14,6% glomerulonephritis 6,2% and Willms tu 4,1%. Reflux nephropathy was also the most common underlying disease of TRF accounted for 36,9% of total cases while glomerulonephritis was responsible for 23,9 %. Reflux nephropathy was associated with neural tube defect in 53,3% and with congenital lower urinary tract obstruction in 66,7%. The most of CRF (81,25% and TRF pts (95,6% were from Serbia, the others were from Monte Negro and Republic Srpska. The most of CRF (65% and TRF (80% pts were treated in University Children’s Hospital in Belgrade. Of CRF pts 46% had serum sreatinine 100-200 μmol/l, in 11% of pts it was 400-600 μmol/l and 2% of pts were in pre-terminal CRF. One third of CRF pts had proteinuria 150-500 mg/l, and second third had proteinuria greater of 1000 mg/l. Anemia was present in 54% of CRf pts, and arterial hypertension in 56%. Hemodialysis was dominant treatment modality for TRF pts and only 23,9% had functioning transplant. Conclusion: This is the first national study of demographic characteristics of pediatric CRF in Serbia. Since its prevalence is considerably lower than that in Western and North European countries the true prevalence is some what higher. The increasing incidence of pediatric TRF from 2

  12. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    OpenAIRE

    Andreas Stengel; Yvette F. Taché; Yvette F. Taché

    2017-01-01

    Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a br...

  13. Four Closely Related HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Identified in East China.

    Science.gov (United States)

    Li, Fan; Li, Yuxueyun; Feng, Yi; Hu, Jing; Ruan, Yuhua; Xing, Hui; Shao, Yiming

    2017-07-01

    Five near full-length genomes of novel second-generation HIV-1 recombinant virus (JS150021, JS150029, JS150129, JS150132, and AH150183) were identified from five HIV-positive people in Jiangsu and Anhui province, east China. Phylogenic analyses showed that these five sequences are all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, grouped into four new discovered recombinant forms, which show several very similar but not identical recombinant breakpoints. The four recombinant forms are also identified to be a sort of family or related viruses, seems to be the results of different recombination events. The emergence of a serious new closely related CRF07_BC/CRF01_AE recombinant strain indicates the increasing complexity of sexual transmission of the HIV-1 epidemic in China.

  14. Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum

    NARCIS (Netherlands)

    Gounko, Natalia V.; Gramsbergen, Albert; van der Want, Johannes J. L.

    The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRF-R2 alpha is present. In the cerebellum, CRF-R2 alpha has two different isoforms: a full-length form (fl) and truncated (tr). Both forms CRF-R2 have a unique

  15. Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption.

    Science.gov (United States)

    Pucci, Mariangela; Micioni Di Bonaventura, Maria Vittoria; Giusepponi, Maria Elena; Romano, Adele; Filaferro, Monica; Maccarrone, Mauro; Ciccocioppo, Roberto; Cifani, Carlo; D'Addario, Claudio

    2016-11-01

    Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds. © 2015 Society for the Study of Addiction.

  16. Expansion of the CRF19_cpx Variant in Spain.

    Science.gov (United States)

    Patiño Galindo, Juan Angel; Torres-Puente, Manoli; Gimeno, Concepción; Ortega, Enrique; Navarro, David; Galindo, María José; Navarro, Laura; Navarro, Vicente; Juan, Amparo; Belda, Josefina; Bracho, María Alma; González-Candelas, Fernando

    2015-08-01

    HIV-1 CRF19_cpx, is a recombinant variant found almost exclusively in Cuba and recently associated to a faster AIDS onset. Infection with this variant leads to higher viral loads and levels of RANTES and CXCR4 co-receptor use. The goal of this study was to assess the presence of CRF19_cpx in the Spanish province of Valencia, given its high pathogenicity. 1294 HIV-1 protease-reverse transcriptase (PR/RT) sequences were obtained in Valencia (Spain), between 2005 and 2014. After subtyping, the detected CRF19_cpx sequences were aligned with 201 CRF19_cpx and 66 subtype D sequences retrieved from LANL, and subjected to maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. The presence of resistance mutations in the PR/RT region of these sequences was also analyzed. Among the 9 CRF19_cpx sequences from different patients found (prevalence <0.1%), 7 grouped in two well-supported clades (groups A, n=4, and B, n=3), suggesting the existence of at least two independent introductions which subsequently started to expand in the studied Spanish region. Unprotected sex between men was the only known transmission route. Coalescent analyses suggested that the introductions in Valencia occurred between 2008 and 2010. Resistance mutations in the RT region were found in all sequences from group A (V139D) and in two sequences from group B (E138A). This study reports for the first time the recent expansion of CRF19_cpx outside Cuba. Our results suggest that CRF19_cpx might become an emerging HIV variant in Spain, affecting Spanish native MSM and not only Cuban migrants. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Activation of corticotropin-releasing factor receptors from the basolateral or central amygdala increases the tonic immobility response in guinea pigs: an innate fear behavior.

    Science.gov (United States)

    Donatti, Alberto Ferreira; Leite-Panissi, Christie Ramos Andrade

    2011-11-20

    The tonic immobility (TI) behavior is an innate response associated with extreme threat situations such as a predator attack. Several studies have provided evidence suggesting an important role for corticotropin-releasing factor (CRF) in the regulation of the endocrine system, defensive behaviors and behavioral responses to stress. TI has been shown to be positively correlated with the basal plasma levels of corticosterone. CRF receptors and neurons that are immunoreactive to CRF are found in many cerebral regions, especially in the amygdaloid complex. Previous reports have demonstrated the involvement of the basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI response. In this study, we evaluated the CRF system of the BLA and the CeA in the modulation of the TI response in guinea pigs. The activation of CRF receptors in the BLA and in the CeA promoted an increase in the TI response. In contrast, the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the duration of the TI response. Moreover, neither the activation nor inhibition of CRF receptors in the BLA or the CeA altered spontaneous motor activity in the open-field test. These data suggest that the activation of the CRF receptors in the BLA or the CeA probably potentiates fear and anxiety, which may be one of the factors that promote an increase in the TI behavior. Therefore, these data support the role of the CRF system in the control of emotional responses, particularly in the modulation of innate fear. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

    Science.gov (United States)

    Bryce, Courtney A; Floresco, Stan B

    2016-07-01

    Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.

  19. Internalization of the human CRF receptor 1 is independent of classical phosphorylation sites and of beta-arrestin 1 recruitment

    DEFF Research Database (Denmark)

    Rasmussen, Trine N; Novak, Ivana; Nielsen, Søren M

    2004-01-01

    The corticotropin releasing factor receptor 1 (CRFR1) belongs to the superfamily of G-protein coupled receptors. Though CRF is involved in the aetiology of several stress-related disorders, including depression and anxiety, details of CRFR1 regulation such as internalization remain uncharacterized...

  20. A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells.

    Science.gov (United States)

    Pelissier-Rota, M; Chartier, N T; Bonaz, B; Jacquier-Sarlin, M R

    2017-07-01

    Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction. Non-neuronal acetylcholine (Ach) and muscarinic receptors (mAchR) also contribute to alterations of epithelial cell functions. In this study, we investigated the mechanisms through which stress and Ach modulate epithelial cell adhesive properties. We show that Ach-induced activation of mAchR in HT-29 cells results in cell dissociation together with changes in cell-matrix contacts, which correlates with the acquisition of invasive potential consistent with a matrix metalloproteinase (MMP) mode of invasion. These processes result from mAchR subsequent stimulation of the cascade of src/Erk and FAK activation. Ach-induced secretion of laminin 332 leads to α3β1 integrin activation and RhoA-dependent reorganization of the actin cytoskeleton. We show that Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling. This is reinforced by the fact that Ach-mediated activation of mAchR stimulates both the synthesis and the release of CRF2 ligands in HT-29 cells (effects blocked by atropine). In summary, our data provides evidence for a novel intracellular circuit involving mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier dysfunction and exacerbate mucosal inflammation. Copyright © 2017. Published by Elsevier B.V.

  1. Distribution of corticotropin-releasing factor receptors in primate brain

    International Nuclear Information System (INIS)

    Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

    1986-01-01

    The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [ 125 I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 0 C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress

  2. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    Science.gov (United States)

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  3. Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity.

    Science.gov (United States)

    Howerton, Alexis R; Roland, Alison V; Fluharty, Jessica M; Marshall, Anikò; Chen, Alon; Daniels, Derek; Beck, Sheryl G; Bale, Tracy L

    2014-06-01

    Women are twice as likely as men to suffer from stress-related affective disorders. Corticotropin-releasing factor (CRF) is an important link between stress and mood, in part through its signaling in the serotonergic dorsal raphe (DR). Development of CRF receptor-1 (CRFr1) antagonists has been a focus of numerous clinical trials but has not yet been proven efficacious. We hypothesized that sex differences in CRFr1 modulation of DR circuits might be key determinants in predicting therapeutic responses and affective disorder vulnerability. Male and female mice received DR infusions of the CRFr1 antagonist, NBI 35965, or CRF and were evaluated for stress responsivity. Sex differences in indices of neural activation (cFos) and colocalization of CRFr1 throughout the DR were examined. Whole-cell patch-clamp electrophysiology assessed sex differences in serotonin neuron membrane characteristics and responsivity to CRF. Males showed robust behavioral and hypothalamic-pituitary-adrenal axis responses to DR infusion of NBI 35965 and CRF, whereas females were minimally responsive. Sex differences were also found for both CRF-induced DR cFos and CRFr1 co-localization throughout the DR. Electrophysiologically, female serotonergic neurons showed blunted membrane excitability and divergent inhibitory postsynaptic current responses to CRF application. These studies demonstrate convincing sex differences in CRFr1 activity in the DR, where blunted female responses to NBI 35965 and CRF suggest unique stress modulation of the DR. These sex differences might underlie affective disorder vulnerability and differential sensitivity to pharmacologic treatments developed to target the CRF system, thereby contributing to a current lack of CRFr1 antagonist efficacy in clinical trials. © 2013 Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

  4. Human factors information system

    International Nuclear Information System (INIS)

    Goodman, P.C.; DiPalo, C.A.

    1991-01-01

    Nuclear power plant safety is dependent upon human performance related to plant operations. To provide improvements in human performance, data collection and assessment play key roles. This paper reports on the Human factors Information System (HFIS) which is designed to meet the needs of the human factors specialists of the United States Nuclear Regulatory Commission. These specialists identify personnel errors and provide guidance designed to prevent such errors. HFIS is a simple and modular system designed for use on a personal computer. It is designed to contain four separate modules that provide information indicative of program or function effectiveness as well as safety-related human performance based on programmatic and performance data. These modules include the Human Factors Status module; the Regulatory Programs module; the Licensee Event Report module; and the Operator Requalification Performance module. Information form these modules can either be used separately or can be combined due to the integrated nature of the system. HFIS has the capability, therefore, to provide insights into those areas of human factors that can reduce the probability of events caused by personnel error at nuclear power plants and promote the health and safety of the public. This information system concept can be applied to other industries as well as the nuclear industry

  5. Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

    Science.gov (United States)

    Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

    2007-02-01

    Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

  6. The effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.

    Science.gov (United States)

    Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

    2013-10-01

    To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea. After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia. Primate research center. Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4). Five days of diet in a novel room with unfamiliar conspecifics. Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus. The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals. The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval.

    Science.gov (United States)

    Janitzky, K; Peine, A; Kröber, A; Yanagawa, Y; Schwegler, H; Roskoden, T

    2014-10-01

    The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice. Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure. Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Molecular detection of HIV-1 subtype B, CRF01_AE, CRF33_01B, and newly emerging recombinant lineages in Malaysia.

    Science.gov (United States)

    Chook, Jack Bee; Ong, Lai Yee; Takebe, Yutaka; Chan, Kok Gan; Choo, Martin; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-03-01

    A molecular genotyping assay for human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia is difficult to design because of the high level of genetic diversity. We developed a multiplex real-time polymerase chain reaction (PCR) assay to detect subtype B, CRF01_AE, CRF33_01B, and three newly described circulating recombinant forms, (CRFs) (CRF53_01B, CRF54_01B, and CRF58_01B). A total of 785 reference genomes were used for subtype-specific primers and TaqMan probes design targeting the gag, pol, and env genes. The performance of this assay was compared and evaluated with direct sequencing and phylogenetic analysis. A total of 180 HIV-infected subjects from Kuala Lumpur, Malaysia were screened and 171 samples were successfully genotyped, in agreement with the phylogenetic data. The HIV-1 genotype distribution was as follows: subtype B (16.7%); CRF01_AE (52.8%); CRF33_01B (24.4%); CRF53_01B (1.1%); CRF54_01B (0.6%); and CRF01_AE/B unique recombinant forms (4.4%). The overall accuracy of the genotyping assay was over 95.0%, in which the sensitivities for subtype B, CRF01_AE, and CRF33_01B detection were 100%, 100%, and 97.7%, respectively. The specificity of genotyping was 100%, inter-subtype specificities were > 95% and the limit of detection of 10(3) copies/mL for plasma. The newly developed real-time PCR assay offers a rapid and cost-effective alternative for large-scale molecular epidemiological surveillance for HIV-1. © The American Society of Tropical Medicine and Hygiene.

  9. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    Directory of Open Access Journals (Sweden)

    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  10. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

    Science.gov (United States)

    Stengel, Andreas; Taché, Yvette F

    2017-01-01

    Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  11. The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

    Science.gov (United States)

    Schwandt, Melanie L; Cortes, Carlos R; Kwako, Laura E; George, David T; Momenan, Reza; Sinha, Rajita; Grigoriadis, Dimitri E; Pich, Emilio Merlo; Leggio, Lorenzo; Heilig, Markus

    2016-01-01

    Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21–65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced alcohol craving and relapse. PMID:27109623

  12. Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder

    Science.gov (United States)

    Bremner, J. Douglas; Licinio, Julio; Darnell, Adam; Krystal, John H.; Owens, Michael J.; Southwick, Steven M.; Nemeroff, Charles B.; Charney, Dennis S.

    2011-01-01

    Objective Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. Method Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N=11) and comparison subjects (N=17). CSF concentrations of CRF and somatostatin were compared between the two groups. Results CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean=29.0 pg/ml, SD=7.8, versus mean=21.9 pg/ml, SD=6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean=19.9 pg/ml, SD=5.4, versus mean=13.7 pg/ml, SD=8.0). However, covarying for age reduced the level of significance. Conclusions Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD. PMID:9137116

  13. Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving.

    Science.gov (United States)

    Epstein, David H; Kennedy, Ashley P; Furnari, Melody; Heilig, Markus; Shaham, Yavin; Phillips, Karran A; Preston, Kenzie L

    2016-12-01

    In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. To test anticraving properties of the CRF 1 antagonist pexacerfont in humans. We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS). The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r effect  = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect  = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics. The findings may support further investigation of the anticraving properties of CRF 1 antagonists, especially for food.

  14. The effects of corticotrophin-releasing factor and two antagonists on breathing movements in fetal sheep.

    Science.gov (United States)

    Bennet, L; Johnston, B M; Vale, W W; Gluckman, P D

    1990-01-01

    1. The respiratory effects of corticotrophin-releasing factor (CRF) and the CRF antagonists alpha-helical CRF 9-41 (alpha hCRF) and [DPhe 12, Nle 21-38] rCRF (12-41) (DPhe CRF) have been studied in unanaesthetized fetal lambs of 125-140 days gestation. 2. CRF when given as a 10 micrograms bolus followed by a 5 micrograms h-1 infusion into a lateral cerebral ventricle caused prolonged continuous fetal breathing movements which were stimulated in both amplitude and frequency but which did not persist during hypoxia. 3. Lower doses of CRF (20 ng bolus followed by 10 ng h-1) increased the amplitude but not the frequency of fetal breathing movements which did not become continuous. 4. At higher doses (20 micrograms bolus followed by 10-15 micrograms h-1) CRF induced cerebral convulsions which were also associated with fetal breathing movements of increased amplitude and frequency. 5. The CRF antagonists alpha hCRF and DPhe CRF both inhibited fetal breathing movements and induced a prolonged apnoea which was resistant to the stimulatory effects of 5-6% hypercapnia. 6. We conclude that CRF stimulates breathing movements in the fetal lamb. The finding that administration of the CRF antagonists alone cause apnoea suggests that CRF may have a tonic role in the regulation of fetal breathing movements. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:2348387

  15. The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

    Science.gov (United States)

    Valero, E; Gómez-Milanés, I; Almela, P; Ribeiro Do Couto, B; Laorden, M L; Milanés, M V; Núñez, C

    2018-06-08

    Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse

  16. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  17. Enduring Effects Of Traumatic Stress On Brain Neuropeptide Y (NPY) and Corticotropin-Releasing Factor (CRF) Systems: Molecular and Neuropharmacologic Studies

    Science.gov (United States)

    2009-12-01

    epoch consisted of a single daily defeat episode as described above on 3 consecutive days. Between each epoch, there was a time-out period of 3 days...2.5 weeks after the final defeat (data not shown). Treatment with twice daily imipramine (i.p., 2.5 mg/kg) for 2.5 weeks, eliminated the effects of...time course of immediate early gene expression in rat brain following acute stress. Neuroscience 64:477–505. ayas CV, Buller KM, Day TA (1999

  18. Molecular epidemiology of HIV type 1 infection in Iran: genomic evidence of CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use.

    Science.gov (United States)

    Jahanbakhsh, Fatemeh; Ibe, Shiro; Hattori, Junko; Monavari, Seyed Hamid Reza; Matsuda, Masakazu; Maejima, Masami; Iwatani, Yasumasa; Memarnejadian, Arash; Keyvani, Hossein; Azadmanesh, Kayhan; Sugiura, Wataru

    2013-01-01

    To understand the molecular epidemiology of HIV-1 infection in Iran, we conducted the first study to analyze the genome sequence of Iranian HIV-1 isolates. For this cross-sectional study, we enrolled 10 HIV-1-infected individuals associated with injection drug use from Tehran, Shiraz, and Kermanshah. Near full-length genome sequences obtained from their plasma samples were used for phylogenetic tree and similarity plotting analyses. Among 10 isolates, nine were clearly identified as CRF35_AD and the remaining one as CRF01_AE. Interestingly, five of our Iranian CRF35_AD isolates made two clusters with 10 Afghan CRF35_AD isolates in a phylogenetic tree, indicating epidemiological connections among injection drug users in Iran and Afghanistan. In contrast, our CRF01_AE isolate had no genetic relationship with any other CRF01_AE isolates worldwide, even from Afghanistan. This study provides the first genomic evidence of HIV-1 CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use in Iran.

  19. Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin

    Science.gov (United States)

    Martin-Fardon, Rémi; Zorrilla, Eric P.; Ciccocioppo, Roberto; Weiss, Friedbert

    2010-01-01

    Stress-like symptoms are an integral part of acute and protracted drug withdrawal, and several lines of evidence have shown that dysregulation of brain stress systems, including the extrahypothalamic corticotropin-releasing factor (CRF) system, following long-term drug use is of major importance in maintaining drug and alcohol addiction. Recently, two other neuropeptide systems have attracted interest, the nociceptin/orphanin FQ (N/OFQ) and orexin/hypocretin (Orx/Hcrt) systems. N/OFQ participates in a wide range of physiological responses, and the hypothalamic Orx/Hcrt system helps regulate several physiological processes, including feeding, energy metabolism, and arousal. Moreover, these two systems have been suggested to participate in psychiatric disorders, including anxiety and drug addiction. Dysregulation of these systems by chronic drug exposure has been hypothesized to play a role in the maintenance of addiction and dependence. Recent evidence demonstrated that interactions between CRF-N/OFQ and CRF-Orx/Hcrt systems may be functionally relevant for the control of stress-related addictive behavior. The present review discusses recent findings that support the hypotheses of the participation and dysregulation of these systems in drug addiction and evaluates the current understanding of interactions among these stress-regulatory peptides. PMID:20026088

  20. Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

    Directory of Open Access Journals (Sweden)

    Schulkin Jay

    2006-04-01

    Full Text Available Abstract Background Corticotropin-releasing factor (CRF is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior. Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl or amphetamine (20 μg/0.2 μl. Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng or amphetamine (20 μg selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress

  1. Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

    Science.gov (United States)

    Peciña, Susana; Schulkin, Jay; Berridge, Kent C

    2006-04-13

    Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 microg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to

  2. Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE

    OpenAIRE

    Poljak, Mario; Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Stuck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie; Alexiev, Ivailo

    2016-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap...

  3. Corticotropin-Releasing Factor Receptors Modulate Oxytocin Release in the Dorsolateral Bed Nucleus of the Stria Terminalis (BNST in Male Rats

    Directory of Open Access Journals (Sweden)

    Daisy Martinon

    2018-03-01

    Full Text Available The neuropeptide oxytocin (OT plays an important role in the regulation of social and anxiety-like behavior. Our previous studies have shown that OT neurons send projections from the hypothalamus to the dorsolateral bed nucleus of the stria terminalis (BNSTdl, a forebrain region critically involved in the modulation of anxiety-like behavior. Importantly, these OT terminals in the BNSTdl express presynaptic corticotropin releasing factor (CRF receptor type 2 (CRFR2. This suggests that CRFR2 might be involved in the modulation of OT release. To test this hypothesis, we measured OT content in microdialysates collected from the BNSTdl of freely-moving male Sprague-Dawley rats following the administration of a selective CRFR2 agonist (Urocortin 3 or antagonist (Astressin 2B, As2B. To determine if type 1 CRF receptors (CRFR1 are also involved, we used selective CRFR1 antagonist (NBI35965 as well as CRF, a putative ligand of both CRFR1 and CRFR2. All compounds were delivered directly into the BNSTdl via reverse dialysis. OT content in the microdialysates was measured with highly sensitive and selective radioimmunoassay. Blocking CRFR2 with As2B caused an increase in OT content in BNSTdl microdialysates, whereas CRFR2 activation by Urocortin 3 did not have an effect. The As2B-induced increase in OT release was blocked by application of the CRFR1 antagonist demonstrating that the effect was dependent on CRFR1 transmission. Interestingly, CRF alone caused a delayed increase in OT content in BNSTdl microdialysates, which was dependent on CRF2 but not CRF1 receptors. Our results suggest that members of the CRF peptide family modulate OT release in the BNSTdl via a fine-tuned mechanism that involves both CRFR1 and CRFR2. Further exploration of mechanisms by which endogenous OT system is modulated by CRF peptide family is needed to better understand the role of these neuropeptides in the regulation of anxiety and the stress response.

  4. Acute and repeated ECS treatment increases CRF, POMC and PENK gene expression in selected regions of the rat hypothalamus.

    Science.gov (United States)

    Garcia-Garcia, L; Llewellyn-Jones, V; Fernandez Fernandez, I; Fuentes, J A; Manzanares, J

    1998-01-05

    The purpose of this study was to investigate the effects of acute and repeated electroconvulsive shock (ECS) on corticotropin releasing factor (CRF), proopiomelanocortin (POMC) and proenkephalin (PENK) gene expression in selected regions of the brain and pituitary of the rat. Acute ECS increased CRF gene expression in the paraventricular nucleus (PVN) by 20%, an effect that was further enhanced to 38% when rats received repeated ECS treatment. Acute and repeated ECS increased POMC gene expression in the arcuate nucleus (ARC) by 49-59% but failed to alter these mRNA levels in the anterior lobe (AL) of the pituitary gland. PENK gene expression was increased by 35% in the nucleus accumbens (NA) and by 180% the ventromedial nucleus (VMN) after acute or repeated ECS treatment but no significant changes were found in the PVN or striatum (ST). Taken together, these results indicate a differential CRF and opioid gene expression regulation after acute or repeated ECS treatment that may be relevant to their therapeutic or side effects in depression.

  5. A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype.

    Science.gov (United States)

    Schroeder, Mariana; Jakovcevski, Mira; Polacheck, Tamar; Lebow, Maya; Drori, Yonat; Engel, Mareen; Ben-Dor, Shifra; Chen, Alon

    2017-06-06

    Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3. Moreover, exposing the offspring to a methyl-balanced diet during adolescence prevents the dysregulation and predisposition from being triggered. We demonstrate that gestational programming, per se, will not lead to BE-like behavior, but pre-existing alterations due to prenatal programming are revealed only when challenged during adolescence. We provide experimental evidence for long-term epigenetic abnormalities stemming from PNS in predisposing female offspring to BE disorder as well as a potential non-invasive prevention strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

    2001-09-01

    To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

  7. Regulation and Roles of Urocortins in the Vascular System

    Directory of Open Access Journals (Sweden)

    Kazunori Kageyama

    2012-01-01

    Full Text Available Urocortins (Ucns are members of the corticotropin-releasing factor (CRF family of peptides. Ucns would have potent effects on the cardiovascular system via the CRF receptor type 2 (CRF2 receptor. Regulation and roles of each Ucn have been determined in the vascular system. Ucns have more potent vasodilatory effects than CRF. Human umbilical vein endothelial cells (HUVECs express Ucns1-3 mRNAs, and the receptor, CRF2a receptor mRNA. Ucns1-3 mRNA levels are differentially regulated in HUVECs. Differential regulation of Ucns may suggest differential roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL-6 gene expression and secretion in rat aortic smooth muscle A7r5 cells. The increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells suggests that smooth muscle cells may be a source of IL-6 secretion under physiological stress conditions. Ucns are important and unique modulators of vascular smooth muscle cells and act directly or indirectly as autocrine and paracrine factors in the vascular system.

  8. Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum

    NARCIS (Netherlands)

    Swinny, JD; Kalicharan, D; Blaauw, EH; Ijkema-Paassen, J; Shi, F; Gramsbergen, A; van der Want, JJL

    Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but

  9. Phylodynamic analysis of the dissemination of HIV-1 CRF01_AE in Vietnam.

    Science.gov (United States)

    Liao, Huanan; Tee, Kok Keng; Hase, Saiki; Uenishi, Rie; Li, Xiao-Jie; Kusagawa, Shigeru; Thang, Pham Hong; Hien, Nguyen Tran; Pybus, Oliver G; Takebe, Yutaka

    2009-08-15

    To estimate the epidemic history of HIV-1 CRF01_AE in Vietnam and adjacent Guangxi, China, we determined near full-length nucleotide sequences of CRF01_AE from a total of 33 specimens collected in 1997-1998 from different geographic regions and risk populations in Vietnam. Phylogenetic and Bayesian molecular clock analyses were performed to estimate the date of origin of CRF01_AE lineages. Our study reconstructs the timescale of CRF01_AE expansion in Vietnam and neighboring regions and suggests that the series of CRF01_AE epidemics in Vietnam arose by the sequential introduction of founder strains into new locations and risk groups. CRF01_AE appears to have been present among heterosexuals in South-Vietnam for more than a decade prior to its epidemic spread in the early 1990s. In the late 1980s, the virus spread to IDUs in Southern Vietnam and subsequently in the mid-1990s to IDUs further north. Our results indicate the northward dissemination of CRF01_AE during this time.

  10. Evidence for possible biological advantages of the newly emerging HIV-1 circulating recombinant form from Malaysia - CRF33_01B in comparison to its progenitors - CRF01_AE and subtype B.

    Science.gov (United States)

    Lau, Katherine A; Wang, Bin; Miranda-Saksena, Monica; Boadle, Ross; Kamarulzaman, Adeeba; Ng, Kee-Peng; Saksena, Nitin K

    2010-04-01

    In Malaysia, co-circulation of CRF01_AE and subtype B has resulted in the emergence of the second generation derivative; CRF33_01B in approximately 20% of its HIV-1 infected individuals. Our objective was to identify possible biological advantages that CRF33_01B possesses over its progenitors. Biological and molecular comparisons of CRF33_01B against its parental subtypes clearly show that CRF33_01B replicated better in activated whole peripheral blood mononuclear cells (PBMCs) and CD4+ T-lymphocytes, but not monocyte-derived macrophages (MDMs). Also, its acquired fitness was greater than CRF01_AE but not subtype B. Moreover, CRF33_01B has higher rate of apoptotic cell death and syncytia induction compared to subtype B. These adaptive and survival abilities could have been acquired by CRF33_01B due to the incorporation of subtype B fragments into the gag-RT region of its full-length genome. Our studies confirm the previously held belief that HIV-1 strains may harbor enhanced biological fitness upon recombination. We therefore estimate a possible gradual replacement of the current predominance of CRF01_AE, as well as wider dissemination of CRF33_01B, together with the identification of other new CRF01_AE/B inter-subtype recombinants in Malaysia.

  11. Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats.

    Science.gov (United States)

    Blacktop, Jordan M; Vranjkovic, Oliver; Mayer, Matthieu; Van Hoof, Matthew; Baker, David A; Mantsch, John R

    2016-03-01

    Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1.0 mg/kg/ing; 14 × 6 h/day) and extinction and were tested for reinstatement in response to footshock (0.5 mA, 0.5" duration, average every 40 s; range 10-70 s) or intra-VTA CRF delivery (500 ng/side) following intra-VTA pretreatment with the GABA-A antagonist, bicuculline, the GABA-B antagonist, 2-hydroxysaclofen or vehicle. Intra-VTA bicuculline (1, 10 or 20 ng/side) failed to block footshock- or CRF-induced cocaine seeking at either dose tested. By contrast, 2-hydroxysaclofen (0.2 or 2 μg/side) prevented reinstatement by both footshock and intra-VTA CRF at a concentration that failed to attenuate food-reinforced lever pressing (45 mg sucrose-sweetened pellets; FR4 schedule) in a separate group of rats. These data suggest that GABA-B receptor-dependent CRF actions in the VTA mediate stress-induced cocaine seeking and that GABA-B receptor antagonists may have utility for the management of stress-induced relapse in cocaine addicts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. HIV-1 CRF_BC recombinants infection in China: molecular epidemic and characterizations.

    Science.gov (United States)

    Ouyang, Yabo; Shao, Yiming; Ma, Liying

    2012-03-01

    CRF_BC recombinant strains were first identified in China and are one of the most prevalent and characteristically unique HIV-1 subtypes across China. Here we aim to review the published data about HIV-1 CRF_BC recombinant strains epidemic in China and to characterize the genetics, biology and drug resistance of this virus. This study may help to better understand the current situation of HIV-1 CRF_BC prevalence and facilitate the development of vaccines and more efficient anti-HIV-1 regimens in China.

  13. Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health.

    Science.gov (United States)

    Janssen, Donny; Kozicz, Tamás

    2013-01-01

    Physiological responses to stress coordinated by the hypothalamo-pituitary-adrenal axis are concerned with maintaining homeostasis in the presence of real or perceived challenges. Regulators of this axis are corticotrophin releasing factor (CRF) and CRF related neuropeptides, including urocortins 1, 2, and 3. They mediate their actions by binding to CRF receptors (CRFR) 1 and 2, which are located in several stress-related brain regions. The prevailing theory has been that the initiation of and the recovery from an elicited stress response is coordinated by two elements, viz. the (mainly) opposing, but well balanced actions of CRFR1 and CRFR2. Such a dualistic view suggests that CRF/CRFR1 controls the initiation of, and urocortins/CRFR2 mediate the recovery from stress to maintain body and mental health. Consequently, failed adaptation to stress can lead to neuropathology, including anxiety and depression. Recent literature, however, challenges such dualistic and complementary actions of CRFR1 and CRFR2, and suggests that stress recruits CRF system components in a brain area and neuron specific manner to promote adaptation as conditions dictate.

  14. Laos Organization Name Using Cascaded Model Based on SVM and CRF

    Directory of Open Access Journals (Sweden)

    Duan Shaopeng

    2017-01-01

    Full Text Available According to the characteristics of Laos organization name, this paper proposes a two layer model based on conditional random field (CRF and support vector machine (SVM for Laos organization name recognition. A layer of model uses CRF to recognition simple organization name, and the result is used to support the decision of the second level. Based on the driving method, the second layer uses SVM and CRF to recognition the complicated organization name. Finally, the results of the two levels are combined, And by a subsequent treatment to correct results of low confidence recognition. The results show that this approach based on SVM and CRF is efficient in recognizing organization name through open test for real linguistics, and the recalling rate achieve 80. 83%and the precision rate achieves 82. 75%.

  15. Robust rooftop extraction from visible band images using higher order CRF

    KAUST Repository

    Li, Er; Femiani, John; Xu, Shibiao; Zhang, Xiaopeng; Wonka, Peter

    2015-01-01

    In this paper, we propose a robust framework for building extraction in visible band images. We first get an initial classification of the pixels based on an unsupervised presegmentation. Then, we develop a novel conditional random field (CRF

  16. The CRF-method for semiconductors' intravalley collision kernels: I – the 2D case

    Directory of Open Access Journals (Sweden)

    Claudio Barone

    1992-05-01

    Full Text Available If the collisions are redefined as a flux a kinetic conservation law can be written in divergence form. This can be handled numerically, in the framework of Finite Particle Approximation, using the CRF-method. In the present paper the relevant quantities needed for computer implementation of the CRF-method are derived in the case of a 2D momentum space for the semiconductors' intravalley collision kernels.

  17. The CRF-method for semiconductors' intravalley collision kernels: II – The 3D case

    Directory of Open Access Journals (Sweden)

    Claudio Barone

    1993-05-01

    Full Text Available If the collisions are redefined as a flux a kinetic conservation law can be written in divergence form. This can be handled numerically, in the framework of Finite Particle Approximation, using the CRF-method. In this paper we use the CRF-method for semiconductors' intravalley collision kernels. We extend the results obtained in a previous paper to the case of a 3D momentum space.

  18. Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan.

    Directory of Open Access Journals (Sweden)

    Yue Chen

    Full Text Available A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%, together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15% but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a while 12 (38% were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan.

  19. Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan

    Science.gov (United States)

    Chen, Yue; Hora, Bhavna; DeMarco, Todd; Shah, Sharaf Ali; Ahmed, Manzoor; Sanchez, Ana M.; Su, Chang; Carter, Meredith; Stone, Mars; Hasan, Rumina; Hasan, Zahra; Busch, Michael P.; Denny, Thomas N.; Gao, Feng

    2016-01-01

    A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%), together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a) within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15%) but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a) while 12 (38%) were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan. PMID:27973597

  20. Short Communication: Reassessing the Origin of the HIV-1 CRF02_AG Lineages Circulating in Brazil.

    Science.gov (United States)

    Delatorre, Edson; Velasco-De-Castro, Carlos A; Pilotto, José H; Couto-Fernandez, José Carlos; Bello, Gonzalo; Morgado, Mariza G

    2015-12-01

    HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil. As more CRF02_AG samples have been identified in Brazil, we performed a new phylogeographic analysis using a larger dataset than before. A total of 20 Brazilian (18 from Rio de Janeiro and two from São Paulo) and 1,485 African HIV-1 CRF02_AG pol sequences were analyzed using maximum likelihood (ML). The ML tree showed that the Brazilian sequences were distributed in five different lineages. The Bayesian phylogeographic analysis of the Brazilian and their most closely related African sequences (n = 212) placed the origin of all Brazilian lineages in West Africa, probably Ghana, Senegal, and Nigeria. Two monophyletic clades were identified, comprising only sequences from Rio de Janeiro, and their date of origin was estimated at around 1985 (95% highest posterior density: 1979-1992). These results support the existence of at least five independent introductions of the CRF02_AG lineage from West Africa into Brazil and further indicate that at least two of these lineages have been locally disseminated in the Rio de Janeiro state over the past 30 years.

  1. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    International Nuclear Information System (INIS)

    Perna, A.F.; Smogorzewski, M.; Massry, S.G.

    1988-01-01

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

  2. Expression and hypophysiotropic actions of corticotropin-releasing factor in Xenopus laevis.

    Science.gov (United States)

    Boorse, Graham C; Denver, Robert J

    2004-07-01

    Members of the corticotropin-releasing factor (CRF) family of peptides play pivotal roles in the regulation of neuroendocrine, autonomic, and behavioral responses to physical and emotional stress. In amphibian tadpoles, CRF-like peptides stimulate both thyroid and interrenal (adrenal) hormone secretion, and can thereby modulate the rate of metamorphosis. To better understand the regulation of expression and actions of CRF in amphibians we developed a homologous radioimmunoassay (RIA) for Xenopus laevis CRF (xCRF). We validated this RIA and tissue extraction procedure for the measurement of brain CRF content in tadpoles and juveniles. We show that the CRF-binding protein, which is highly expressed in X. laevis brain, is largely removed by acid extraction and does not interfere in the RIA. We analyzed CRF peptide content in five microdissected brain regions in prometamorphic tadpoles and juveniles. CRF was detected throughout the brain, consistent with its role as both a hypophysiotropin and a neurotransmitter/neuromodulator. CRF content was highest in the region of the preoptic area (POa) and increased in all brain regions after metamorphosis. Exposure to 4h of handling/shaking stress resulted in increased CRF peptide content in the POa in juvenile frogs. Injections of xCRF into prometamorphic tadpoles increased whole body corticosterone and thyroxine content, thus supporting findings in other anuran species that this peptide functions as both a corticotropin- and a thyrotropin (TSH)-releasing factor. Furthermore, treatment of cultured tadpole pituitaries with xCRF (100nM for 24h) resulted in increased medium content, but decreased pituitary content of TSHbeta-immunoreactivity. Our results support the view that CRF functions as a stress neuropeptide in X. laevis as in other vertebrates. Furthermore, we provide evidence for a dual hypophysiotropic action of CRF on the thyroid and interrenal axes in X. laevis as has been shown previously in other amphibian species.

  3. Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.

    Science.gov (United States)

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M; Rice, Kenner C; Ubaldi, Massimo; St Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin; Cifani, Carlo

    2014-08-20

    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders. Copyright © 2014 the authors 0270-6474/14/3411316-09$15.00/0.

  4. Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

    Directory of Open Access Journals (Sweden)

    Paula Madeira Fortes

    2017-06-01

    Full Text Available Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation, or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF and brain-derived neurotrophic factor (BNDF were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

  5. Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Mahanand Chatoo

    2018-02-01

    Full Text Available Irritable bowel syndrome (IBS is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized. Corticotropin-releasing factor (CRF, a major mediator in the stress response, is involved in altered function in GI, including inflammatory processes, colonic transit time, contractile activity, defecation pattern, pain threshold, mucosal secretory function, and barrier functions. This mini review focuses on the recently establish local GI-CRF system, its involvement in modulating the immune response in IBS, and summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF and receptors might be a key molecule involving the immune and movement function via brain–gut axis in IBS.

  6. Isolation and characterization of a replication-competent molecular clone of an HIV-1 circulating recombinant form (CRF33_01B.

    Directory of Open Access Journals (Sweden)

    Kok Keng Tee

    Full Text Available A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1, a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5' LTR (long terminal repeat region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone, showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia.

  7. Robust rooftop extraction from visible band images using higher order CRF

    KAUST Repository

    Li, Er

    2015-08-01

    In this paper, we propose a robust framework for building extraction in visible band images. We first get an initial classification of the pixels based on an unsupervised presegmentation. Then, we develop a novel conditional random field (CRF) formulation to achieve accurate rooftops extraction, which incorporates pixel-level information and segment-level information for the identification of rooftops. Comparing with the commonly used CRF model, a higher order potential defined on segment is added in our model, by exploiting region consistency and shape feature at segment level. Our experiments show that the proposed higher order CRF model outperforms the state-of-the-art methods both at pixel and object levels on rooftops with complex structures and sizes in challenging environments. © 1980-2012 IEEE.

  8. Corticotropin-releasing factor receptors in the pituitary gland and central nervous system: methods and overview

    International Nuclear Information System (INIS)

    De Souza, E.B.; Kuhar, M.J.

    1986-01-01

    Studies with the radioiodinated oCRF analog, Nle21, 125I-Tyr32-oCRF have identified, characterized, and localized high affinity binding sites for CRF in anterior and intermediate lobes of rat pituitary, in anterior lobe of human pituitary, and in rat, monkey, and human brain. The pharmacology and distribution of Nle21, 125I-Tyr32-oCRF binding in the pituitary gland correlate well with the biological potency and sites of action of CRF and suggest that these CRF binding sites represent specific receptors that mediate the well-established actions of CRF on the anterior pituitary and on the intermediate lobe of the pituitary. The studies in adrenalectomized rats demonstrating that endogenous CRF is capable of modulating its receptor density provide additional evidence that the radioligand labels the functional CRF receptor. The areas of distribution of Nle21, 125I-Tyr32-oCRF binding sites in the rat CNS correlate well with the immunohistochemical distribution of CRF pathways and the pharmacological sites of action of CRF. These data confirm the established role of CRF in regulating secretion of POMC-derived peptides from the pituitary gland. In addition, the data support a physiological role for endogenous CRF in regulating CNS activity and suggest the importance of this neuropeptide in integrating endocrine and visceral functions and behavior, especially in response to stress. Studies to characterize CRF receptors and CRF-containing pathways in the brain provide a means for better understanding the various functions of this neuropeptide in different areas of the CNS. Finally, the ability to map CRF receptors in postmortem human tissue provides a basis for studying the role of CRF in a variety of endocrine, neurological, and psychiatric disorders

  9. Local Optogenetic Induction of Fast (20-40 Hz Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

    Directory of Open Access Journals (Sweden)

    Julien eDine

    2016-04-01

    Full Text Available The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2 expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz field potential oscillations in hippocampal area CA1 in vitro (at 25°C and in vivo (i.e., slightly anaesthetized NEX-Cre-ChR2 mice. As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  10. Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity.

    Science.gov (United States)

    Dine, Julien; Genewsky, Andreas; Hladky, Florian; Wotjak, Carsten T; Deussing, Jan M; Zieglgänsberger, Walter; Chen, Alon; Eder, Matthias

    2016-01-01

    The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells) and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM) in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC) in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1→PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive) P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  11. SEMANTIC LABELLING OF ULTRA DENSE MLS POINT CLOUDS IN URBAN ROAD CORRIDORS BASED ON FUSING CRF WITH SHAPE PRIORS

    Directory of Open Access Journals (Sweden)

    W. Yao

    2017-09-01

    Full Text Available In this paper, a labelling method for the semantic analysis of ultra-high point density MLS data (up to 4000 points/m2 in urban road corridors is developed based on combining a conditional random field (CRF for the context-based classification of 3D point clouds with shape priors. The CRF uses a Random Forest (RF for generating the unary potentials of nodes and a variant of the contrastsensitive Potts model for the pair-wise potentials of node edges. The foundations of the classification are various geometric features derived by means of co-variance matrices and local accumulation map of spatial coordinates based on local neighbourhoods. Meanwhile, in order to cope with the ultra-high point density, a plane-based region growing method combined with a rule-based classifier is applied to first fix semantic labels for man-made objects. Once such kind of points that usually account for majority of entire data amount are pre-labeled; the CRF classifier can be solved by optimizing the discriminative probability for nodes within a subgraph structure excluded from pre-labeled nodes. The process can be viewed as an evidence fusion step inferring a degree of belief for point labelling from different sources. The MLS data used for this study were acquired by vehicle-borne Z+F phase-based laser scanner measurement, which permits the generation of a point cloud with an ultra-high sampling rate and accuracy. The test sites are parts of Munich City which is assumed to consist of seven object classes including impervious surfaces, tree, building roof/facade, low vegetation, vehicle and pole. The competitive classification performance can be explained by the diverse factors: e.g. the above ground height highlights the vertical dimension of houses, trees even cars, but also attributed to decision-level fusion of graph-based contextual classification approach with shape priors. The use of context-based classification methods mainly contributed to smoothing of

  12. Semantic Labelling of Ultra Dense Mls Point Clouds in Urban Road Corridors Based on Fusing Crf with Shape Priors

    Science.gov (United States)

    Yao, W.; Polewski, P.; Krzystek, P.

    2017-09-01

    In this paper, a labelling method for the semantic analysis of ultra-high point density MLS data (up to 4000 points/m2) in urban road corridors is developed based on combining a conditional random field (CRF) for the context-based classification of 3D point clouds with shape priors. The CRF uses a Random Forest (RF) for generating the unary potentials of nodes and a variant of the contrastsensitive Potts model for the pair-wise potentials of node edges. The foundations of the classification are various geometric features derived by means of co-variance matrices and local accumulation map of spatial coordinates based on local neighbourhoods. Meanwhile, in order to cope with the ultra-high point density, a plane-based region growing method combined with a rule-based classifier is applied to first fix semantic labels for man-made objects. Once such kind of points that usually account for majority of entire data amount are pre-labeled; the CRF classifier can be solved by optimizing the discriminative probability for nodes within a subgraph structure excluded from pre-labeled nodes. The process can be viewed as an evidence fusion step inferring a degree of belief for point labelling from different sources. The MLS data used for this study were acquired by vehicle-borne Z+F phase-based laser scanner measurement, which permits the generation of a point cloud with an ultra-high sampling rate and accuracy. The test sites are parts of Munich City which is assumed to consist of seven object classes including impervious surfaces, tree, building roof/facade, low vegetation, vehicle and pole. The competitive classification performance can be explained by the diverse factors: e.g. the above ground height highlights the vertical dimension of houses, trees even cars, but also attributed to decision-level fusion of graph-based contextual classification approach with shape priors. The use of context-based classification methods mainly contributed to smoothing of labelling by removing

  13. Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.

    Science.gov (United States)

    Wagle, Mahendra; Mathur, Priya; Guo, Su

    2011-01-05

    The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.

  14. Leads Detection Using Mixture Statistical Distribution Based CRF Algorithm from Sentinel-1 Dual Polarization SAR Imagery

    Science.gov (United States)

    Zhang, Yu; Li, Fei; Zhang, Shengkai; Zhu, Tingting

    2017-04-01

    Synthetic Aperture Radar (SAR) is significantly important for polar remote sensing since it can provide continuous observations in all days and all weather. SAR can be used for extracting the surface roughness information characterized by the variance of dielectric properties and different polarization channels, which make it possible to observe different ice types and surface structure for deformation analysis. In November, 2016, Chinese National Antarctic Research Expedition (CHINARE) 33rd cruise has set sails in sea ice zone in Antarctic. Accurate leads spatial distribution in sea ice zone for routine planning of ship navigation is essential. In this study, the semantic relationship between leads and sea ice categories has been described by the Conditional Random Fields (CRF) model, and leads characteristics have been modeled by statistical distributions in SAR imagery. In the proposed algorithm, a mixture statistical distribution based CRF is developed by considering the contexture information and the statistical characteristics of sea ice for improving leads detection in Sentinel-1A dual polarization SAR imagery. The unary potential and pairwise potential in CRF model is constructed by integrating the posteriori probability estimated from statistical distributions. For mixture statistical distribution parameter estimation, Method of Logarithmic Cumulants (MoLC) is exploited for single statistical distribution parameters estimation. The iteration based Expectation Maximal (EM) algorithm is investigated to calculate the parameters in mixture statistical distribution based CRF model. In the posteriori probability inference, graph-cut energy minimization method is adopted in the initial leads detection. The post-processing procedures including aspect ratio constrain and spatial smoothing approaches are utilized to improve the visual result. The proposed method is validated on Sentinel-1A SAR C-band Extra Wide Swath (EW) Ground Range Detected (GRD) imagery with a

  15. A newly emerging HIV-1 recombinant lineage (CRF58_01B) disseminating among people who inject drugs in Malaysia.

    Science.gov (United States)

    Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

  16. A newly emerging HIV-1 recombinant lineage (CRF58_01B disseminating among people who inject drugs in Malaysia.

    Directory of Open Access Journals (Sweden)

    Wei Zhen Chow

    Full Text Available The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K and to date 55 circulating recombinant forms (CRFs. In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B, CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%, CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258. Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

  17. Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A.; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I.

    2015-01-01

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R–OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–CRF1R–OX1R complex promotes a long-term disruption of the orexin-A–CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. PMID:25926444

  18. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

    2015-04-29

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

  19. Emerging Role for Corticotropin Releasing Factor Signaling in the Bed Nucleus of the Stria Terminalis at the Intersection of Stress and Reward

    Directory of Open Access Journals (Sweden)

    Yuval eSilberman

    2013-05-01

    Full Text Available Stress and anxiety play an important role in the development and maintanence of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST, a brain region involved in the production of long-term stress related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF as being critically important in BNST mediated reinstatement behaviors. The BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types and there has only been limited work trying to understand how CRF modulates this complex neuronal system. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of BNST CRF signaling in drug addiction and reinstatment with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

  20. Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2013-01-01

    Stress and anxiety play an important role in the development and maintenance of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST), a brain region involved in the production of long-term stress-related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF) as being critically important in BNST-mediated reinstatement behaviors. Although numerous studies indicate that the BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types, there has only been limited work to determine how CRF modulates this complex neuronal system at the circuit level. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of CRF signaling in drug addiction and reinstatement with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

  1. CDC Behavioral Risk Factor Surveillance System (BRFSS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Behavioral Risk Factor Surveillance System (BRFSS) is a state-based system of health surveys that collects information on health risk behaviors, preventive...

  2. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Peptide YY, neuropeptide Y and corticotrophin-releasing factor modulate gastrointestinal motility and food intake during acute stress.

    Science.gov (United States)

    Forbes, Sarah C; Cox, Helen M

    2014-11-01

    Peripheral neuropeptide Y (NPY) provides protection against the endocrine, feeding and gastrointestinal (GI) responses to stress; however, it is not yet established how it interacts with corticotrophin-releasing factor (CRF) to mediate these effects. Peptide YY (PYY) also has significant roles in GI motility and food intake but little is known about its role in stress responses. Upper GI transit, fecal pellet output (FPO) and feeding responses, and the role of CRF1 receptors, during restraint or a novel environment stress, were ascertained in PYY-/-, NPY-/- and wild type (WT) mice, with CRF and the CRF1 antagonist, antalarmin, injected intraperitoneally. Upper GI transit and FPO were significantly increased in PYY-/- mice during restraint stress. Exogenous CRF increased defecation during placement in a novel environment in WT mice through CRF1 , while CRF1 blockade reduced defecation in WT and NPY-/- mice but had no effect in PYY-/- mice. In addition, CRF1 blockade had no effect on upper GI transit in WT mice, or on food intake in PYY-/- or NPY-/- mice, but it significantly increased food intake in WT mice. Endogenous NPY appears to inhibit the colonic motor response induced by CRF1 activation, unlike PYY, while both peptides are required for CRF1 modulation of feeding behavior during stress. Overall, these results provide new insights into the mechanism by which PYY and NPY affect stress responses. © 2014 John Wiley & Sons Ltd.

  4. Early Life Stress as a Risk Factor for Substance use Disorders: Clinical and Neurobiological Substrates

    OpenAIRE

    Varghese, Sajoy Purathumuriyil; Montalvo-Ortiz, Janitza L.; Csernansky, John G.; Eiger, Rodney I.; Herrold, Amy A.; Koola, Maju Mathew; Dong, Hongxin

    2015-01-01

    Background: Early Life Stress (ELS) can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Materials and Methods: Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA) was used for...

  5. Survivability of systems under multiple factor impact

    International Nuclear Information System (INIS)

    Korczak, Edward; Levitin, Gregory

    2007-01-01

    The paper considers vulnerable multi-state series-parallel systems operating under influence of external impacts. Both the external impacts and internal failures affect system survivability, which is determined as the probability of meeting a given demand. The external impacts are characterized by several destructive factors affecting the system or its parts simultaneously. In order to increase the system's survivability a multilevel protection against the destructive factors can be applied to its subsystems. In such systems, the protected subsystems can be destroyed only if all of the levels of their protection are destroyed. The paper presents an algorithm for evaluating the survivability of series-parallel systems with arbitrary configuration of multilevel protection against multiple destructive factor impacts. The algorithm is based on a composition of Boolean and the Universal Generating Function techniques. Illustrative examples are presented

  6. Virulence Factors IN Fungi OF Systemic Mycoses

    Directory of Open Access Journals (Sweden)

    KUROKAWA Cilmery Suemi

    1998-01-01

    Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

  7. Factorizations of one-dimensional classical systems

    International Nuclear Information System (INIS)

    Kuru, Senguel; Negro, Javier

    2008-01-01

    A class of one-dimensional classical systems is characterized from an algebraic point of view. The Hamiltonians of these systems are factorized in terms of two functions that together with the Hamiltonian itself close a Poisson algebra. These two functions lead directly to two time-dependent integrals of motion from which the phase motions are derived algebraically. The systems so obtained constitute the classical analogues of the well known factorizable one-dimensional quantum mechanical systems

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

    Science.gov (United States)

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

    2018-06-01

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

  9. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

    Science.gov (United States)

    Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-03-01

    Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

  10. Validation of human factor engineering integrated system

    International Nuclear Information System (INIS)

    Fang Zhou

    2013-01-01

    Apart from hundreds of thousands of human-machine interface resources, the control room of a nuclear power plant is a complex system integrated with many factors such as procedures, operators, environment, organization and management. In the design stage, these factors are considered by different organizations separately. However, whether above factors could corporate with each other well in operation and whether they have good human factors engineering (HFE) design to avoid human error, should be answered in validation of the HFE integrated system before delivery of the plant. This paper addresses the research and implementation of the ISV technology based on case study. After introduction of the background, process and methodology of ISV, the results of the test are discussed. At last, lessons learned from this research are summarized. (authors)

  11. Study on the chronic inflammatory status in patients with chronic renal failure (CRF)

    International Nuclear Information System (INIS)

    Deng Lirong; Wang Caili; Wei Hong; Yang Yuhua

    2005-01-01

    Objective: To study the relationship between the status of chronic inflammation and deterioration of renal function in patients with chronic renal failure (CRF). Methods: Serum CRP, IL-10 (with ELISA), TNF-α, IL-6 (with RIA) and creatinine (with bio-chemistry methods) levels were determined in 126 patients with CRF of various stages as well as in 30 controls. The creatinine clearance rate (CCr) was also calculated. Results: (1)In all these patients, the serum CRP, IL-6, IL-10 and TNF-α contents were significantly higher than those in the controls (P <0.01). (2) CRP, IL-6, IL-10 and TNF-α levels were linearly positively correlated with the creatinine levels (r= 0.716, 0.836, 0.501 and 0.574 respectively), linearly negatively correlated with the creatinine clearance rate (r=-0.755, -0.825, -0.497 and -0.564 respectively). As the renal function deteriorated progressively, the serum levels of CRP, IL-6, IL-10 and TNF-α increased correspondingly. (3) The acute phase protein CRP and inflammatory cytokines IL-6 and TNF-α levels were correlated with those of the anti-inflammatory cytokine IL-10 (r=0.463, 0.546 and 0.402 respectively). Conclusion: The serum acute phase protein CRP, inflammatory cytokines IL-6, TNF-α and anti-inflammatory cytokine IL-10 contents were all gradually increased along with the progression of CRF and these inflammatory mediators were mutually positively correlated with each other. (authors)

  12. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    International Nuclear Information System (INIS)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-01-01

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  13. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  14. A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

    KAUST Repository

    Huang, Yangjie

    2016-04-13

    This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

  15. A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

    KAUST Repository

    Huang, Yangjie; Ajitha, Manjaly John; Huang, Kuo-Wei; Zhang, Zhongxing; Weng, Zhiqiang

    2016-01-01

    This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

  16. The PIANC Safety Factor System for Breakwaters

    DEFF Research Database (Denmark)

    Burcharth, H. F.

    2000-01-01

    The paper presents a summary of the recommendations for implementation of safety in breakwater designs given by the PIANC PTC IT Working Group No 12 on Analysis of Rubble Mound Breakwaters with Vertical and Inclined Concrete Walls. The working groups developed for the most important failure modes...... a system of partial safety factors which facilitate design to any target safety level....

  17. Cooperative mobility systems: The human factor challenges.

    NARCIS (Netherlands)

    Martens, Marieke; Kroon, Elisabeth

    2014-01-01

    This paper presents a vision on cooperative mobility systems from a human factors perspective. To create a common ground for future developments, it’s important to define the common research themes and knowledge gaps. This article presents what steps need to be taken in order to come to proper

  18. Environmental Factors, Toxicants and Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Anselm Mak

    2014-09-01

    Full Text Available Systemic lupus erythematosus (SLE is an immune-complex-mediated multi-systemic autoimmune condition of multifactorial etiology, which mainly affects young women. It is currently believed that the onset of SLE and lupus flares are triggered by various environmental factors in genetically susceptible individuals. Various environmental agents and toxicants, such as cigarette smoke, alcohol, occupationally- and non-occupationally-related chemicals, ultraviolet light, infections, sex hormones and certain medications and vaccines, have been implicated to induce SLE onset or flares in a number case series, case-control and population-based cohort studies and very few randomized controlled trials. Here, we will describe some of these recognized environmental lupus triggering and perpetuating factors and explain how these factors potentially bias the immune system towards autoimmunity through their interactions with genetic and epigenetic alterations. Further in-depth exploration of how potentially important environmental factors mechanistically interact with the immune system and the genome, which trigger the onset of SLE and lupus flares, will certainly be one of the plausible steps to prevent the onset and to decelerate the progress of the disease.

  19. Low-Grade Glioma Segmentation Based on CNN with Fully Connected CRF

    Directory of Open Access Journals (Sweden)

    Zeju Li

    2017-01-01

    Full Text Available This work proposed a novel automatic three-dimensional (3D magnetic resonance imaging (MRI segmentation method which would be widely used in the clinical diagnosis of the most common and aggressive brain tumor, namely, glioma. The method combined a multipathway convolutional neural network (CNN and fully connected conditional random field (CRF. Firstly, 3D information was introduced into the CNN which makes more accurate recognition of glioma with low contrast. Then, fully connected CRF was added as a postprocessing step which purposed more delicate delineation of glioma boundary. The method was applied to T2flair MRI images of 160 low-grade glioma patients. With 59 cases of data training and manual segmentation as the ground truth, the Dice similarity coefficient (DSC of our method was 0.85 for the test set of 101 MRI images. The results of our method were better than those of another state-of-the-art CNN method, which gained the DSC of 0.76 for the same dataset. It proved that our method could produce better results for the segmentation of low-grade gliomas.

  20. Global dispersal pattern of HIV type 1 subtype CRF01-AE : A genetic trace of human mobility related to heterosexual sexual activities centralized in southeast Asia

    NARCIS (Netherlands)

    Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie M J; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Camacho, Ricardo J.; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kostrikis, Leondios G.; Lepej, Snjezana; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Boucher, Charles A B; Kaplan, Lauren; Vandamme, Anne Mieke; Paraskevis, Dimitrios

    2015-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01-AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01-AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set

  1. Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159.

    Directory of Open Access Journals (Sweden)

    Estibaliz Lazaro

    Full Text Available BACKGROUND: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding. METHODS: We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores and HLA binding (MHC score. RESULTS: All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9 versus 2 (±0.7 in non-divergent ones (p<0.0001. CONCLUSIONS: Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area.

  2. PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

    International Nuclear Information System (INIS)

    Sullivan, Gregory M.; Parsey, Ramin V.; Kumar, J.S. Dileep; Arango, Victoria; Kassir, Suham A.; Huang, Yung-yu; Simpson, Norman R.; Van Heertum, Ronald L.; Mann, J. John

    2007-01-01

    Aim: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [ 11 C]R121920 and [ 11 C]DMP696 in the nonhuman primate for application in positron emission tomography (PET) studies of CRF1. Methods: PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET. Results: Both [ 11 C]R121920 and [ 11 C]DMP696 distributed rapidly and uniformly throughout the brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [ 125 I]Tyr 0 -sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (B max ) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded B max of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K D ) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore, B max and K D were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. Conclusion: Neither [ 11 C]R121920 nor [ 11 C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum

  3. Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain.

    Science.gov (United States)

    Rotllant, David; Nadal, Roser; Armario, Antonio

    2007-05-01

    Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

  4. Influence of the shot-peening treatment on the CRF gearing behaviour

    International Nuclear Information System (INIS)

    Molinie, D.; Lemaire, E.; Randrianarivo, L.; Dorier, C.

    1998-01-01

    Surface damage are observed in service on CRF case-hardened cases. Such damage is like surface fatigue which appears in the form of frosting and can come to a micro-spalling or even a spalling damage. Survey and studies realised on gears affected by such damage, led EDF and the manufacturer to search for appropriated solutions since 1985 (optimisation of the gear bottom profile, care of the grinding and the thermochemical processing, use of oils with higher viscosity). Simulations on a running wheel device can reproduce the meshing conditions on simplified specimen. The aim is to study the influence of residual stresses following a severe grinding and shot peening treatments. An empiric selection was realised among different shot peening treatments. Endurance tests are realised on case-hardened gears with or without shot-peening treatments. Compared with standard grinded gears, it appears that the shot-peening selected increases up to 40% the gear lifetime till extended spalling. (authors)

  5. LU factorization for accelerator-based systems

    KAUST Repository

    Agullo, Emmanuel

    2011-12-01

    Multicore architectures enhanced with multiple GPUs are likely to become mainstream High Performance Computing (HPC) platforms in a near future. In this paper, we present the design and implementation of an LU factorization using tile algorithm that can fully exploit the potential of such platforms in spite of their complexity. We use a methodology derived from previous work on Cholesky and QR factorizations. Our contributions essentially consist of providing new CPU/GPU hybrid LU kernels, studying the impact on performance of the looking variants as well as the storage layout in presence of pivoting, tuning the kernels for two different machines composed of multiple recent NVIDIA Tesla S1070 (four GPUs total) and Fermi-based S2050 GPUs (three GPUs total), respectively. The hybrid tile LU asymptotically achieves 1 Tflop/s in single precision on both hardwares. The performance in double precision arithmetic reaches 500 Gflop/s on the Fermi-based system, twice faster than the old GPU generation of Tesla S1070. We also discuss the impact of the number of tiles on the numerical stability. We show that the numerical results of the tile LU factorization will be accurate enough for most applications as long as the computations are performed in double precision arithmetic. © 2011 IEEE.

  6. Electromagnetic form factors of composite systems

    International Nuclear Information System (INIS)

    Nowak, E.J.

    1978-01-01

    Electromagnetic form factors are examined for a spin-zero, two-body composite system with emphasis on the case of small momentum transfer and/or deep (relativistic) binding. Perturbation theory calculations are first performed using spin-zero and then spin-one-half constituents. A dispersion representation of the bound-state vertex function is conjectured first for scalar and then for fermion constituents. Then a relativistic effective range approximation (RERA) is developed for each case and applied to the calculation of the electromagnetic form factor. The approach is applied to the study of the charge radii of the K 0 and K + mesons. The K/sub l3/ form factor is calculated in the fermion constituent RERA model, and restrictions are imposed on the model parameters from available experimental data. With these restrictions the limits 0.24fm less than or equal to √[abs. value ( 2 >/sub K 0 /)] less than or equal to = 0.36fm and 0.66fm less than or equal to = √( 2 >/sub K + /) less than or equal to 0.79fm are obtained for the kaon charge radii, and -.22 less than or equal to xi less than or equal to -.13 is found for the ratio of the neutral to charged kaon charge radius squared

  7. Anatomical Organization of Urocortin 3-Synthesizing Neurons and Immunoreactive Terminals in the Central Nervous System of Non-Human Primates [Sapajus spp.

    Directory of Open Access Journals (Sweden)

    Daniella S. Battagello

    2017-07-01

    Full Text Available Urocortin 3 (UCN3 is a neuropeptide member of the corticotropin-releasing factor (CRF peptide family that acts as a selective endogenous ligand for the CRF, subtype 2 (CRF2 receptor. Immunohistochemistry and in situ hybridization data from rodents revealed UCN3-containing neurons in discrete regions of the central nervous system (CNS, such as the medial preoptic nucleus, the rostral perifornical area (PFA, the medial nucleus of the amygdala and the superior paraolivary nucleus. UCN3-immunoreactive (UCN3-ir terminals are distributed throughout regions that mostly overlap with regions of CRF2 messenger RNA (mRNA expression. Currently, no similar mapping exists for non-human primates. To better understand the role of this neuropeptide, we aimed to study the UCN3 distribution in the brains of New World monkeys of the Sapajus genus. To this end, we analyzed the gene and peptide sequences in these animals and performed immunohistochemistry and in situ hybridization to identify UCN3 synthesis sites and to determine the distribution of UCN3-ir terminals. The sequencing of the Sapajus spp. UCN3-coding gene revealed 88% and 65% identity to the human and rat counterparts, respectively. Additionally, using a probe generated from monkey cDNA and an antiserum raised against human UCN3, we found that labeled cells are mainly located in the hypothalamic and limbic regions. UCN3-ir axons and terminals are primarily distributed in the ventromedial hypothalamic nucleus (VMH and the lateral septal nucleus (LS. Our results demonstrate that UCN3-producing neurons in the CNS of monkeys are phylogenetically conserved compared to those of the rodent brain, that the distribution of fibers agrees with the distribution of CRF2 in other primates and that there is anatomical evidence for the participation of UCN3 in neuroendocrine control in primates.

  8. Sex differences in the locus coeruleus-norepinephrine system and its regulation by stress.

    Science.gov (United States)

    Bangasser, Debra A; Wiersielis, Kimberly R; Khantsis, Sabina

    2016-06-15

    Women are more likely than men to suffer from post-traumatic stress disorder (PTSD) and major depression. In addition to their sex bias, these disorders share stress as an etiological factor and hyperarousal as a symptom. Thus, sex differences in brain arousal systems and their regulation by stress could help explain increased vulnerability to these disorders in women. Here we review preclinical studies that have identified sex differences in the locus coeruleus (LC)-norepinephrine (NE) arousal system. First, we detail how structural sex differences in the LC can bias females towards increased arousal in response to emotional events. Second, we highlight studies demonstrating that estrogen can increase NE in LC target regions by enhancing the capacity for NE synthesis, while reducing NE degradation, potentially increasing arousal in females. Third, we review data revealing how sex differences in the stress receptor, corticotropin releasing factor 1 (CRF1), can increase LC neuronal sensitivity to CRF in females compared to males. This effect could translate into hyperarousal in women under conditions of CRF hypersecretion that occur in PTSD and depression. The implications of these sex differences for the treatment of stress-related psychiatric disorders are discussed. Moreover, the value of using information regarding biological sex differences to aid in the development of novel pharmacotherapies to better treat men and women with PTSD and depression is also highlighted. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Success Factors of Business Process Management Systems Implementation

    NARCIS (Netherlands)

    Johan Versendaal; J.P.P. Ravesteijn

    2007-01-01

    In this research (critical) success factors for Business Process Management Systems implementation are identified and qualitatively validated. Furthermore a list of critical success factors is constructed. Based on the identified factors a BPMS implementation approach is suggested. Future research

  10. Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

    Science.gov (United States)

    Flandreau, Elizabeth I.; Bourke, Chase H.; Ressler, Kerry J.; Vale, Wylie W.; Nemeroff, Charles B.; Owens, Michael J.

    2013-01-01

    Summary We have previously demonstrated that viral-mediated overexpression of corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) reproduces many of the behavioral and endocrine consequences of chronic stress. The present experiment sought to determine whether administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram reverses the adverse effects of CeA CRF overexpression. In a 2 × 2 design, adult male rats received bilateral infusions of a control lentivirus or a lentivirus in which a portion of the CRF promoter is used to drive increased expression of CRF peptide. Four weeks later, rats were then implanted with an Alzet minipump to deliver vehicle or 10 mg/kg/day escitalopram for a 4-week period of time. The defensive withdrawal (DW) test of anxiety and the sucrose-preference test (SPT) of anhedonia were performed both before and after pump implantation. Additional post-implant behavioral tests included the elevated plus maze (EPM) and social interaction (SI) test. Following completion of behavioral testing, the dexamethasone/CRF test was performed to assess HPA axis reactivity. Brains were collected and expression of HPA axis-relevant transcripts were measured using in situ hybridization. Amygdalar CRF overexpression increased anxiety-like behavior in the DW test at week eight, which was only partially prevented by escitalopram. In both CRF-overexpressing and control groups, escitalopram decreased hippocampal CRF expression while increasing hypothalamic and hippocampal expression of the glucocorticoid receptor (GR). These gene expression changes were associated with a significant decrease in HPA axis reactivity in rats treated with escitalopram. Interestingly, escitalopram increased the rate of weight gain only in rats overexpressing CRF. Overall these data support our hypothesis that amygdalar CRF is critical in anxiety-like behavior; because the antidepressant was unable to reverse behavioral

  11. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Science.gov (United States)

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  12. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Directory of Open Access Journals (Sweden)

    Hui Ting Cheong

    Full Text Available In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs. Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs, especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  13. Role of human factors in system safety

    International Nuclear Information System (INIS)

    Brooks, D. M.; Robert, C.; Graham, T.

    2008-01-01

    What happens when technology goes wrong? Three Mile Island, Chernobyl, space shuttles Challenger and Columbia, numerous airplane crashes, and other notable and newsworthy as well as many more incidents that are not reported on the news, have all been attributed to human error. Millions of dollars in fines are levied against industry under the General Duty clause for ergonomic violations, all avoidable. These incidents and situations indicate a lack of consideration for the humans in the system during the design phase. As a consequence, all of these organizations had to retrofit, had to redesign and had to pay countless dollars for medical costs, Worker's Compensation, OSHA fines and in some instances had irrecoverable damage to their public image. Human Factors, otherwise known as Engineering Psychology or Ergonomics, found its origins in loss, loss of life, loss of confidence, loss of technology, loss of property. Without loss, there would be no need for human factors. No one really 'attends' to discomfort...nor are errors attended to that have little consequence. Often it is ultimately the compilation and cumulative effects of these smaller and often ignored occurrences that lead to the bigger and more tragic incidents that make the evening news. When an incident or accident occurs, they are frequently attributed to accomplished, credible, experienced people. In reality however, the crisis was inevitable when a series of events happen such that a human is caught in the whirlwind of accident sequence. The world as known is becoming smaller and more complex. Highly technical societies have been hard at work for several centuries rebuilding the world out of cold steel that is very far removed from ancient instincts and traditions and is becoming more remote to human users. The growth of technology is more than exponential, and is virtually beyond comprehension for many people. Humans, feeling comfortable with the familiar, fulfill their propensity to implement new

  14. The effect of corrosion product CrF3 on thermo-physical properties of FLiNaK

    International Nuclear Information System (INIS)

    Yin Huiqin; Zhang Peng; An Xuehui; Zhao Sufang; Xie Leidong; Wang Wenfeng

    2016-01-01

    FLiNaK (LiF–NaF–KF: 46.5–11.5–42 mol%) is a promising candidate as the secondary loop coolant in molten salt reactor. The thermo-physical properties of pure FLiNaK and FLiNaK containing up to 6000 ppm (equivalent to mg/kg) corrosion product CrF 3 were measured. The results indicate that the effects of CrF 3 on melting point, enthalpy, specific heat capacity, density and thermal diffusivity of FLiNaK in liquid state are negligible within the allowable error range, meanwhile the change of thermal diffusivity is significant for FLiNaK in solid state. This work provides fundamental knowledge for the thermo-physical properties of coolant in molten salt reactor. (author)

  15. Construction and characterization of HIV type 1 CRF07_BC infectious molecular clone from men who have sex with men.

    Science.gov (United States)

    Jiang, Yan-Ling; Bai, Wen-Wei; Qu, Fan-Wei; Ma, Hua; Jiang, Run-Sheng; Shen, Bao-Sheng

    2016-03-01

    This study aimed to investigate the biological characterization of HIV type 1 (HIV-1) CRF07_BC infection among men who have sex with men (MSM). From November 2011 to November 2013, a total of 66 blood samples were collected from MSM with acute HIV-1 infection with CRF07_BC subgroup strains. Deletion in the gag p6 region was detected by sequence alignment and comparative analysis. Peripheral blood mononuclear cells (PBMCs) of HNXX1301-1307 samples were separated by density gradient centrifugation. Nested polymerase chain reaction (nPCR) was used to amplify the viral DNA. The near full-length HIV-1 DNA products were ligated to the long terminal repeat (LTR) vector plasmid (07BCLTR) to construct a full-length HIV clone. The molecular clone was transfected into HEK-293T cells, TZM-b1 cells and patients' PBMCs. The pregenome of an infectious molecular clone of HIV-1 (pNL4-3) was amplified, and a subclone with CRF07_BC was developed to construct the full-length chimeric molecular clone pNL4-3/07BCLTR. Detection of p24 antigen and luciferase activity was used to measure the in vitro infectivity of pNL4-3/07BCLTR. Among the 66 MSM patients infected with CRF07_BC strains, deletion mutations of the Gag P6 proteins were found in 7 of 18CRF07_BC strains; deletion mutations of 2-13 amino acids in different regions were discovered in 6 strains; and the remaining 42 strains did not show deletions. Seven strains with amino acids deficiency in the P6 protein accounted for 27% of all strains and 75% of all deletion genotype strains. A total of 186 full-length molecular clones of CRF07_BC were constructed. There were 5, 9, 10 and 11 clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 that resulted in p24-positive supernatant when transfected into HEK-293T cells. Full-length clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 showed slight infection in the transfected TZM-b1 cells, as judged by the fluorescence values of TZM-b1 cells 48h post-transfection. However, we were unable to

  16. Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients

    Directory of Open Access Journals (Sweden)

    Kazem Baesi

    2014-09-01

    Full Text Available Objective: To identify the dominant subtype among the HIV-1 strains circulation in Iran. Methods: In this cross sectional study 100 HIV positive patients participated. HIV-1 RNA was extracted from plasma. RT nested-PCR was performed and the final products were sequenced and phylogenetically analyzed; reference sequences were downloaded from Los Alamos, aligned with Iranian pol sequences in the study and analyzed by neighbor-joining method. Results: The results of the phylogenetic analysis showed that HIV-1 subtype CRF-35AD was the dominant subtype among HIV-1 infected patients in Iran; this analysis also suggested a new circulating recombinant form that had not previously been identified in Iran: CRF-29BF. Conclusions: The impact of HIV diversity on pathogenesis, transmission and clinical management have been discussed in different studies; therefore, analyses of HIV genetic diversity is required to design effective antiretroviral strategies for different HIV subtypes.

  17. Near Full-Length Identification of a Novel HIV-1 CRF01_AE/B/C Recombinant in Northern Myanmar.

    Science.gov (United States)

    Zhou, Yan-Heng; Chen, Xin; Liang, Yue-Bo; Pang, Wei; Qin, Wei-Hong; Zhang, Chiyu; Zheng, Yong-Tang

    2015-08-01

    The Myanmar-China border appears to be the "hot spot" region for the occurrence of HIV-1 recombination. The majority of the previous analyses of HIV-1 recombination were based on partial genomic sequences, which obviously cannot reflect the reality of the genetic diversity of HIV-1 in this area well. Here, we present a near full-length characterization of a novel HIV-1 CRF01_AE/B/C recombinant isolated from a long-distance truck driver in Northern Myanmar. It is the first description of a near full-length genomic sequence in Myanmar since 2003, and might be one of the most complicated HIV-1 chimeras ever detected in Myanmar, containing four CRF01_AE, six B segments, and five C segments separated by 14 breakpoints throughout its genome. The discovery and characterization of this new CRF01_AE/B/C recombinant indicate that intersubtype recombination is ongoing in Myanmar, continuously generating new forms of HIV-1. More work based on near full-length sequence analyses is urgently needed to better understand the genetic diversity of HIV-1 in these regions.

  18. Urocortin, a CRF-like peptide, restores key indicators of damage in the substantia nigra in a neuroinflammatory model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Biggs Christopher S

    2007-07-01

    Full Text Available Abstract We have recently observed that the corticotrophin releasing hormone (CRF related peptide urocortin (UCN reverses key features of nigrostriatal damage in the hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether similar effects are also evident in the lipopolysaccaride (LPS neuroinflammatory paradigm of Parkinson's disease (PD. To do this we have measured restoration of normal motor behaviour, retention of nigral dopamine (DA and also tyrosine hydroxylase (TH activity. Fourteen days following intranigral injections of LPS and UCN, rats showed only modest circling after DA receptor stimulation with apomorphine, in contrast to those given LPS and vehicle where circling was pronounced. In separate experiments, rats received UCN seven days following LPS, and here apomorphine challenge caused near identical circling intensity to those that received LPS and UCN concomitantly. In a similar and consistent manner with the preservation of motor function, UCN 'protected' the nigra from both DA depletion and loss of TH activity, indicating preservation of DA cells. The effects of UCN were antagonised by the non-selective CRF receptor antagonist α-helical CRF and were not replicated by the selective CRF2 ligand UCN III. This suggests that UCN is acting via CRF1 receptors, which have been shown to be anti-inflammatory in the periphery. Our data therefore indicate that UCN is capable of maintaining adequate nigrostriatal function in vivo, via CRF1 receptors following a neuro-inflammatory challenge. This has potential therapeutic implications in PD.

  19. Learning and CRF-Induced Indecision during Escape and Submission in Rainbow Trout during Socially Aggressive Interactions in the Stress-Alternatives Model

    Directory of Open Access Journals (Sweden)

    Tangi R. Summers

    2017-09-01

    Full Text Available Socially stressful environments induce a phenotypic dichotomy of coping measures for populations in response to a dominant aggressor and given a route of egress. This submission- (Stay or escape-oriented (Escape dichotomy represents individual decision-making under the stressful influence of hostile social environments. We utilized the Stress-Alternatives Model (SAM to explore behavioral factors which might predict behavioral phenotype in rainbow trout. The SAM is a compartmentalized tank, with smaller and larger trout separated by an opaque divider until social interaction, and another divider occluding a safety zone, accessible by way of an escape route only large enough for the smaller fish. We hypothesized that distinctive behavioral responses during the first social interaction would indicate a predisposition for one of the behavioral phenotypes in the subsequent interactions. Surprisingly, increased amount or intensity of aggression received had no significant effect on promoting escape in test fish. In fact, during the first day of interaction, fish that turned toward their larger opponent during attack eventually learned to escape. Escaping fish also learn to monitor the patrolling behavior of aggressors, and eventually escape primarily when they are not being observed. Escape per se, was also predicted in trout exhibiting increased movements directed toward the escape route. By contrast, fish that consistently remained in the tank with the aggressor (Stay showed significantly higher frequency of swimming in subordinate positions, at the top or the bottom of the water column, as well as sitting at the bottom. In addition, a corticotropin-releasing factor (CRF-induced behavior, snap-shake, was also displayed in untreated fish during aggressive social interaction, and blocked by a CRF1 receptor antagonist. Especially prevalent among the Stay phenotype, snap-shake indicates indecision regarding escape-related behaviors. Snap-shake was also

  20. UNIPOLAR, BIPOLAR OR MULTIPOLAR INTERNATIONAL SYSTEM? THE DEFENSE INDUSTRY FACTOR

    OpenAIRE

    ÖZKAN, Gökhan

    2008-01-01

    International system can be defined as a complex system of systems that is comprised of economic, political, scientific, technological and military systems. It is hard to analyze this complex system. It is even harder to forecast its future. Nonetheless, there are factors such as the defense industry and military power that affect the dynamics of the international system much more than other factors. After the Revolution in Military Affairs, which transformed the military paradigm, significa...

  1. Sex differences in stress responses: a critical role for corticotropin-releasing factor.

    Science.gov (United States)

    Bangasser, Debra A; Wiersielis, Kimberly R

    2018-03-01

    Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

  2. Molecular Recognition of Corticotropin releasing Factor by Its G protein-coupled Receptor CRFR1

    Energy Technology Data Exchange (ETDEWEB)

    Pioszak, Augen A.; Parker, Naomi R.; Suino-Powell, Kelly; Xu, H. Eric (Van Andel)

    2009-01-15

    The bimolecular interaction between corticotropin-releasing factor (CRF), a neuropeptide, and its type 1 receptor (CRFR1), a class B G-protein-coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form and two in distinct CRF-bound states. The CRFR1 ECD adopts the alpha-beta-betaalpha fold observed for other class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide-binding site of other class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.

  3. TRANSFER PRICING AS A SYSTEM-FACTOR

    Directory of Open Access Journals (Sweden)

    L. M. Guisin

    2011-01-01

    Full Text Available It is proposed that transfer pricing plays a system-building role for multi-profile commercial banks of today. Bank transfer pricing system properties are outlined. Examples of practical implementation of the transfer pricing to bank activities are brought about. Impact of transferprices on key aspects of the bank management and control system is discussed.

  4. Development of Broadly Neutralizing Antibody Mimitopes for Characterization of CRF01_AE HIV-1 Antibody Responses

    Directory of Open Access Journals (Sweden)

    Jesse V. Schoen

    2017-10-01

    Full Text Available Mapping humoral immune responses to HIV-1 over the course of natural infection is important in understanding epitope exposure in relation to elicitation of broadly neutralizing antibodies (bNAbs, which is considered imperative for effective vaccine design. When analyzing HIV-specific immune responses, the antibody binding profiles may be a correlate for functional antibody activity. In this study, we utilized phage display technology to identify novel mimitopes that may represent Env epitope structures bound by bNAbs directed at V1V2 and V3 domains, CD4 binding site (CD4bs and the membrane proximal external region (MPER of Env. Mimitope sequence motifs were determined for each bNAb epitope. Given the ongoing vaccine development efforts in Thailand, these mimitopes that represent CD4bs and MPER epitopes were used to map immune responses of HIV-1 CRF01_AE-infected individuals with known neutralizing responses from two distinct time periods, 1996-98 and 2012-15. The more contemporary cohort showed an increase in binding breadth with binding observed for all MPER and CD4bs mimitopes, while the older cohort showed only 75% recognition of the CD4bs mimitopes and no MPER mimotope binding. Furthermore, mimitope binding profiles correlated significantly with magnitude (p=0.0036 and breadth (p=0.0358 of neutralization of a multi-subtype Tier 1 panel of pseudoviruses. These results highlight the utility of this mimitope mapping approach for detecting human plasma IgG-specificities that target known neutralizing antibody epitopes, and may also provide an indication of the plasticity of antibody binding within HIV-1 Env neutralization determinants.

  5. Factors Associated with Photovoltaic System Costs (Topical Issues Brief)

    Energy Technology Data Exchange (ETDEWEB)

    Mortensen, J.

    2001-06-12

    A variety of factors can affect the cost of photovoltaic systems. This report analyses the relationship among such factors by using information entered into a voluntary registry of PV systems and performing regression analyses. The results showed statistically significant relationships between photovoltaic system cost and (a) grid connection, (b) installation year, (c) areas where the utility had entered into volume purchasing agreements.

  6. Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naïve patients in southern Spain.

    Science.gov (United States)

    González-Domenech, Carmen M; Viciana, Isabel; Delaye, Luis; Mayorga, María Luisa; Palacios, Rosario; de la Torre, Javier; Jarilla, Francisco; Castaño, Manuel; Del Arco, Alfonso; Clavijo, Encarnación; Santos, Jesús

    2018-01-01

    CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain. The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data. Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART) responded. We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

  7. Molecular Epidemiology of HIV-1 in Jilin Province, Northeastern China: Emergence of a New CRF07_BC Transmission Cluster and Intersubtype Recombinants

    Science.gov (United States)

    Ning, Chuanyi; Feng, Yi; Xie, Cunxin; He, Xiang; Takebe, Yutaka; Sun, Liuyan; Guo, Qi; Xing, Hui; Kalish, Marcia L.; Shao, Yiming

    2014-01-01

    Objective To investigate the HIV-1 molecular epidemiology among newly diagnosed HIV-1 infected persons living in the Jilin province of northeastern China. Methods Plasma samples from 189 newly diagnosed HIV-1 infected patients were collected between June 2010 and August 2011 from all nine cities of Jilin province. HIV-1 nucleotide sequences of gag P17–P24 and env C2–C4 gene regions were amplified using a multiplex RT-PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes. Results Based on all sequences generated, the subtype/CFR distribution was as follows: CRF01_AE (58.1%), CRF07_BC (13.2%), subtype B’ (13.2%), recombinant viruses (8.1%), subtype B (3.7%), CRF02_AG (2.9%), subtype C (0.7%). In addition to finding CRF01_AE strains from previously reported transmission clusters 1, 4 and 5, a new transmission cluster was described within the CRF07_BC radiation. Among 11 different recombinants identified, 10 contained portions of gene regions from the CRF01_AE lineage. CRF02_AG was found to form a transmission cluster of 4 in local Jilin residents. Conclusions Our study presents a molecular epidemiologic investigation describing the complex structure of HIV-1 strains co-circulating in Jilin province. The results highlight the critical importance of continuous monitoring of HIV-infections, along with detailed socio-demographic data, in order to design appropriate prevention measures to limit the spread of new HIV infections. PMID:25356726

  8. Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naïve patients in southern Spain.

    Directory of Open Access Journals (Sweden)

    Carmen M González-Domenech

    Full Text Available CRF19_cpx is a complex circulating recombination form (CRF of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain.The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain. Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data.Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART responded.We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

  9. Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

    Science.gov (United States)

    Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping

    2014-01-01

    Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

  10. Traditional leadership factor in modern local government system in ...

    African Journals Online (AJOL)

    Traditional leadership factor in modern local government system in Ghana: policy Implementation, role conflict and marginalization. ... at promoting education, health and environmental management, are highly commendable in Ghana.

  11. Classification analysis of organization factors related to system safety

    International Nuclear Information System (INIS)

    Liu Huizhen; Zhang Li; Zhang Yuling; Guan Shihua

    2009-01-01

    This paper analyzes the different types of organization factors which influence the system safety. The organization factor can be divided into the interior organization factor and exterior organization factor. The latter includes the factors of political, economical, technical, law, social culture and geographical, and the relationships among different interest groups. The former includes organization culture, communication, decision, training, process, supervision and management and organization structure. This paper focuses on the description of the organization factors. The classification analysis of the organization factors is the early work of quantitative analysis. (authors)

  12. "Actionable" critical success factors for supply chain information system implementations

    NARCIS (Netherlands)

    Denolf, Janne M.; Trienekens, Jacques H.; Nel Wognum, P.M.; Schütz, Verena; Vorst, Van Der Jack G.A.J.; Onno Omta, S.W.F.

    2018-01-01

    Implementing a supply chain information system (SCIS) incurs organizational and technical complexities. For managing these complexities, information system researchers have identified generic critical success factors. However, CSFs are abstract and, therefore, difficult to use in practice. To

  13. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains.

    Science.gov (United States)

    Guimarães, Monick L; Velarde-Dunois, Ketty G; Segurondo, David; Morgado, Mariza G

    2012-01-16

    Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005). These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt) and env regions. Alignment and neighbor-joining (NJ) phylogenetic analyses were established from partial env (n = 37) and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay). The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5%) samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%). Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70.0%) or BF1 recombinant (23.8% vs 30.0%) samples from Bolivia.

  14. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

    Directory of Open Access Journals (Sweden)

    Guimarães Monick L

    2012-01-01

    Full Text Available Abstract Background Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Materials and methods Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005. These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt and env regions. Alignment and neighbor-joining (NJ phylogenetic analyses were established from partial env (n = 37 and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay. The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Results Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5% samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%. Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. Conclusion HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70

  15. Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia.

    Science.gov (United States)

    Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie M J; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Camacho, Ricardo J; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kostrikis, Leondios G; Lepej, Snjezana; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean-Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Boucher, Charles A B; Kaplan, Lauren; Vandamme, Anne-Mieke; Paraskevis, Dimitrios

    2015-06-01

    Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Economic growth factors system: theoretical and methodological aspect

    OpenAIRE

    H.Ya. Hlukha

    2014-01-01

    The aim of the article. The main objective of the article is to create theoretical grounds to build the system of economic growth factors, to modernize their classification, to define exogenous and endogenous factors, to analyze them within the state economic policy structure. The results of the analysis. The article focuses on economic growth factors theoretical studies: - economic growth factors classification characteristics have been highlighted; - various approaches to determine...

  17. Underlying Factors for Practicality of the Production Control Systems

    DEFF Research Database (Denmark)

    Arica, Emrah; Strandhagen, Jan Ola; Hvolby, Hans-Henrik

    2012-01-01

    and communication technology, coordination and feedback, human factors and decision making, and measurement are the identified factors to be taken into account. Industrial interviews with three case companies, that are participating to the research program called The Norwegian Manufacturing Future (SFI NORMAN......This paper gives indications to important factors that must be considered for effectiveness of the production control systems under uncertainty. Five key factors have been identified by the literature study. Production schedule generation and execution approach under uncertainty, information...

  18. Probiotics: beneficial factors of the defence system.

    Science.gov (United States)

    Antoine, Jean Michel

    2010-08-01

    Probiotics, defined as living micro-organisms that provide a health benefit to the host when ingested in adequate amounts, have been used traditionally as food components to help the body to recover from diarrhoea. They are commonly ingested as part of fermented foods, mostly in fresh fermented dairy products. They can interact with the host through different components of the gut defence systems. There is mounting clinical evidence that some probiotics, but not all, help the defence of the host as demonstrated by either a shorter duration of infections or a decrease in the host's susceptibility to pathogens. Different components of the gut barrier can be involved in the strengthening of the body's defences: the gut microbiota, the gut epithelial barrier and the immune system. Many studies have been conducted in normal free-living subjects or in subjects during common infections like the common cold and show that some probiotic-containing foods can improve the functioning of or strengthen the body's defence. Specific probiotic foods can be included in the usual balanced diet of consumers to help them to better cope with the daily challenges of their environment.

  19. Factors influencing the profitability of optimizing control systems

    International Nuclear Information System (INIS)

    Broussaud, A.; Guyot, O.

    1999-01-01

    Optimizing control systems supplement conventional Distributed Control Systems and Programmable Logic Controllers. They continuously implement set points, which aim at maximizing the profitability of plant operation. They are becoming an integral part of modern mineral processing plants. This trend is justified by economic considerations, optimizing control being among the most cost-effective methods of improving metallurgical plant performance. The paper successively analyzes three sets of factors, which influence the profitability of optimizing control systems, and provides guidelines for analyzing the potential value of an optimizing control system at a given operation: external factors, such as economic factors and factors related to plant feed; features of the optimizing control system; and subsequent maintenance of the optimizing control system. It is shown that pay back times for optimization control projects are typically measured in days. The OCS software used by the authors for their applications is described briefly. (author)

  20. The Epidemic History of HIV-1 CRF07_BC in Hetian Prefecture and the Role of It on HIV Spreading in China.

    Science.gov (United States)

    Wu, Jianjun; Guo, Hongxiong; Zhang, Jing; Liu, Xiaoming; Ayoupu, Aideaierli; Shen, Yuelan; Miao, Lifeng; Tang, Jihai; Lei, Yanhua; Su, Bin

    2017-04-01

    CRF07_BC is one of the most prevalent HIV-1 strains in China, and Xinjiang Uygur Autonomous Region has ever been considered to be a second epidemic center after Yunnan Province in previous studies. Here we use HIV-1 pol gene sequences identified from Hetian Prefecture located in Xinjiang Autonomous Region to reconstruct the epidemic history of HIV CRF07_BC strain circulating in this region. We found that CRF07_BC is the predominant HIV-1 form in Hetian Prefecture, and the estimated tMRCA analysis shows that there is no enough evidence supporting Xinjiang Autonomous Region as a second epidemic center of spreading HIV-1. It may imply that every city may be only a point among the HIV spreading network because of the frequent migration of population in the whole country nowadays.

  1. Performance analysis of CRF-based learning for processing WoT application requests expressed in natural language.

    Science.gov (United States)

    Yoon, Young

    2016-01-01

    In this paper, we investigate the effectiveness of a CRF-based learning method for identifying necessary Web of Things (WoT) application components that would satisfy the users' requests issued in natural language. For instance, a user request such as "archive all sports breaking news" can be satisfied by composing a WoT application that consists of ESPN breaking news service and Dropbox as a storage service. We built an engine that can identify the necessary application components by recognizing a main act (MA) or named entities (NEs) from a given request. We trained this engine with the descriptions of WoT applications (called recipes) that were collected from IFTTT WoT platform. IFTTT hosts over 300 WoT entities that offer thousands of functions referred to as triggers and actions. There are more than 270,000 publicly-available recipes composed with those functions by real users. Therefore, the set of these recipes is well-qualified for the training of our MA and NE recognition engine. We share our unique experience of generating the training and test set from these recipe descriptions and assess the performance of the CRF-based language method. Based on the performance evaluation, we introduce further research directions.

  2. Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones.

    Science.gov (United States)

    Wang, Lixin; Goebel-Stengel, Miriam; Yuan, Pu-Qing; Stengel, Andreas; Taché, Yvette

    2017-01-01

    Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting

  3. Patient safety - the role of human factors and systems engineering.

    Science.gov (United States)

    Carayon, Pascale; Wood, Kenneth E

    2010-01-01

    Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety.

  4. Patient Safety: The Role of Human Factors and Systems Engineering

    Science.gov (United States)

    Carayon, Pascale; Wood, Kenneth E.

    2011-01-01

    Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety. PMID:20543237

  5. Factors Affecting Successful Implementation of Hospital Information Systems.

    Science.gov (United States)

    Farzandipur, Mehrdad; Jeddi, Fatemeh Rangraz; Azimi, Esmaeil

    2016-02-01

    Today, the use of information systems in health environments, like any other fields, is necessary and organizational managers are convinced to use these systems. However, managers' satisfaction is not the only factor in successfully implementing these systems and failed information technology projects (IT) are reported despite the consent of the directors. Therefore, this study aims to determine the factors affecting the successful implementation of a hospital information system. The study was carried out as a descriptive method in 20 clinical hospitals that the hospital information system (HIS) was conducted in them. The clinical and paraclinical users of mentioned hospitals are the study group. 400 people were chosen as samples in scientific method and the data was collected using a questionnaire consisted of three main human, managerial and organizational, and technological factors, by questionnaire and interview. Then the data was scored in Likert scale (score of 1 to 5) and were analyzed using the SPSS software. About 75 percent of the population were female, with average work experience of 10 years and the mean age was 30 years. The human factors affecting the success of hospital information system implementation achieved the mean score of 3.5, both organizational and managerial factors 2.9 and technological factors the mean of 3. Human factors including computer skills, perceiving usefulness and perceiving the ease of a hospital information system use are more effective on the acceptance and successful implementation of hospital information systems; then the technological factors play a greater role. It is recommended that for the successful implementation of hospital information systems, most of these factors to be considered.

  6. Surveying the critical success factors of BPM-systems implementation.

    NARCIS (Netherlands)

    Ravesteyn, P.; Batenburg, R.

    2010-01-01

    Purpose – The purpose of this paper is to explore if there is a common ground for the definition of business process management (BPM) and BPM-systems, as well as the critical success factors (CSFs) for BPM-system implementation. A BPM-system implementation framework is validated that classifies the

  7. A Study of Information Systems Outsourcing Influential Factors.

    Science.gov (United States)

    Claver, Enrique; Gonzalez, Reyes; Gasco, Jose; Llopis, Juan

    2002-01-01

    Surveyed information systems managers at Spanish public universities to determine the level of information systems outsourcing. Also determined how factors such as the size of universities and their information systems departments, as well as the degree of involvement of rector's and general manager's teams, influence outsourcing levels. (EV)

  8. Factors that influence the relative use of multiple memory systems.

    Science.gov (United States)

    Packard, Mark G; Goodman, Jarid

    2013-11-01

    Neurobehavioral evidence supports the existence of at least two anatomically distinct "memory systems" in the mammalian brain that mediate dissociable types of learning and memory; a "cognitive" memory system dependent upon the hippocampus and a "stimulus-response/habit" memory system dependent upon the dorsolateral striatum. Several findings indicate that despite their anatomical and functional distinctiveness, hippocampal- and dorsolateral striatal-dependent memory systems may potentially interact and that, depending on the learning situation, this interaction may be cooperative or competitive. One approach to examining the neural mechanisms underlying these interactions is to consider how various factors influence the relative use of multiple memory systems. The present review examines several such factors, including information compatibility, temporal sequence of training, the visual sensory environment, reinforcement parameters, emotional arousal, and memory modulatory systems. Altering these parameters can lead to selective enhancements of either hippocampal-dependent or dorsolateral striatal-dependent memory, and bias animals toward the use of either cognitive or habit memory in dual-solution tasks that may be solved adequately with either memory system. In many learning situations, the influence of such experimental factors on the relative use of memory systems likely reflects a competitive interaction between the systems. Research examining how various factors influence the relative use of multiple memory systems may be a useful method for investigating how these systems interact with one another. Copyright © 2013 Wiley Periodicals, Inc.

  9. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  10. Systems competing for mobile factors: decision making based on hard vs. soft locational factors

    Directory of Open Access Journals (Sweden)

    Clodnițchi Roxana

    2017-12-01

    Full Text Available The paper explores the links between capital relocation and soft locational factors addressing the quality of the business environment and the quality of life within the European Union. System competition is viewed as a competition between countries for the mobile factors capital and labour. The issue of systems competition is topical and insufficiently explored by contemporary literature. The scarcity of scientific papers describing the links between system competition theories and contemporary corporate geography theories, especially of the ones including the analysis of soft location factors, is a challenging aspect, which motivates the choice of this subject. This paper’s primary aim is to deliver an overview of the basic corporate geography conceptions, stressing the importance of soft location factors in today’s competition between systems for the mobile factors capital and labour. The paper further contains an analysis of the correlations between indicators regarding the institutional design of countries as developed by the World Bank (Ease of Doing Business, the Happiness Scale and the latest available data of FDI Stocks for the EU countries (2016. The relevance of such a study is based on the evidence that the contemporary business education relies on an extensive knowledge of the business environment. In the circumstance of similar infrastructural conditions, the main difference between locations is made by soft location factors. Since developed economies are characterised by a high degree of ubiquity of soft factors, the paper concludes that developing and emerging economies should foster the development of their soft location factors.

  11. Theory of ground state factorization in quantum cooperative systems.

    Science.gov (United States)

    Giampaolo, Salvatore M; Adesso, Gerardo; Illuminati, Fabrizio

    2008-05-16

    We introduce a general analytic approach to the study of factorization points and factorized ground states in quantum cooperative systems. The method allows us to determine rigorously the existence, location, and exact form of separable ground states in a large variety of, generally nonexactly solvable, spin models belonging to different universality classes. The theory applies to translationally invariant systems, irrespective of spatial dimensionality, and for spin-spin interactions of arbitrary range.

  12. Factorization approach to superintegrable systems: Formalism and applications

    Energy Technology Data Exchange (ETDEWEB)

    Ballesteros, Á., E-mail: angelb@ubu.es; Herranz, F. J., E-mail: fjherranz@ubu.es [Universidad de Burgos, Departamento de Física (Spain); Kuru, Ş., E-mail: kuru@science.ankara.edu.tr [Ankara University, Department of Physics, Faculty of Science (Turkey); Negro, J., E-mail: jnegro@fta.uva.es [Universidad de Valladolid, Departamento de Física Teórica, Atómica y Óptica (Spain)

    2017-03-15

    The factorization technique for superintegrable Hamiltonian systems is revisited and applied in order to obtain additional (higher-order) constants of the motion. In particular, the factorization approach to the classical anisotropic oscillator on the Euclidean plane is reviewed, and new classical (super) integrable anisotropic oscillators on the sphere are constructed. The Tremblay–Turbiner–Winternitz system on the Euclidean plane is also studied from this viewpoint.

  13. Molecular Diversity of HIV-1 among People Who Inject Drugs in Kuala Lumpur, Malaysia: Massive Expansion of Circulating Recombinant Form (CRF) 33_01B and Emergence of Multiple Unique Recombinant Clusters

    Science.gov (United States)

    Chow, Wei Zhen; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B′ of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B′ (11%) and CRF01_AE (5%)] and CRF01_AE/B′ unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B′ recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the

  14. Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

    Science.gov (United States)

    Chow, Wei Zhen; Ong, Lai Yee; Razak, Siti Humaira; Lee, Yeat Mei; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating

  15. Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF 33_01B and emergence of multiple unique recombinant clusters.

    Directory of Open Access Journals (Sweden)

    Wei Zhen Chow

    Full Text Available Since the discovery of HIV-1 circulating recombinant form (CRF 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11% and CRF01_AE (5%] and CRF01_AE/B' unique recombinants (13% were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the

  16. Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition.

    Science.gov (United States)

    Gibelin, Aude; Parrot, Antoine; Maitre, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand; Fartoukh, Muriel; de Prost, Nicolas

    2016-02-01

    Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+). Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012. The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival. The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

  17. Critical Success Factors of Suggestions Systems. | Marx | IFE ...

    African Journals Online (AJOL)

    A literature study approach is followed to establish which factors contribute to the success and failure of various suggestion systems. It was found ... The value of the paper firstly, shows the importance of creativity and innovation within the organisation's own culture and the framework of a formal suggestion system. Secondly ...

  18. Understanding human factors in cyber security as a dynamic system

    NARCIS (Netherlands)

    Young, H.J.; Vliet, A.J. van; Ven, J.G.S. van de; Jol, S.C.; Broekman, C.C.M.T.

    2018-01-01

    The perspective of human factors is largely missing from the wider cyber security dialogue and its scope is often limited. We propose a framework in which we consider cyber security as a state of a system. System change is brought on by an entity’s behavior. Interventions are ways of changing

  19. Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing.

    Directory of Open Access Journals (Sweden)

    Szu-Wei Huang

    Full Text Available The usefulness of ultra-deep pyrosequencing (UDPS for the diagnosis of HIV-1 drug resistance (DR remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF 07_BC among injection drug users (IDUs in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005 and 3 from late epidemic (collected in 2008 were obtained from treatment-naïve patient's peripheral blood mononuclear cells. Viral RNA was extracted directly from patient's plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs (4.4-47.3 fold. Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01-0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.

  20. Parental LTRs are important in a construct of a stable and efficient replication-competent infectious molecular clone of HIV-1 CRF08_BC.

    Science.gov (United States)

    Zhang, Qiwei; Zhang, Xiaomin; Wu, Hao; Seto, Donald; Zhang, Hao-Jie; Chen, Zhiwei; Wan, Chengsong; Zheng, Bo-Jian

    2012-01-01

    Circulating recombinant forms (CRFs) of HIV-1 have been identified in southern China in recent years. CRF08_BC is one of the most predominant subtypes circulating in China. In order to study HIV subtype biology and to provide a tool for biotechnological applications, the first full-length replication-competent infectious molecular clone harboring CRF08_BC is reported. The construction of this clone pBRGX indicates that a moderate-copy number vector is required for its amplification in E. coli. In addition, it is shown that the parental CRF08_BC LTRs are important for generating this efficient replication-competent infectious clone. These observations may aid in the construction of infectious clones from other subtypes. Both the pBRGX-derived virus and its parental isolate contain CCR5 tropism. Their full-length genomes were also sequenced, analyzed, compared and deposited in GenBank (JF719819 and JF719818, respectively). The availability of pBRGX as the first replication-competent molecular clone of CRF08_BC provides a useful tool for a wide range of studies of this newly emergent HIV subtype, including the development of HIV vaccine candidates, antiviral drug screening and drug resistance analysis.

  1. Rated power factor and excitation system of large turbine generator

    International Nuclear Information System (INIS)

    Tokumitsu, Iwao; Watanabe, Takashi; Banjou, Minoru.

    1979-01-01

    As for the rated power factor of turbine generators for thermal power stations, 90% has been adopted since around 1960. On the other hand, power transmission system has entered 500 kV age, and 1,000 kV transmission is expected in the near future. As for the supply of reactive power from thermal and nuclear turbine generators, the necessity of supplying leading reactive power has rather increased. Now, the operating power factor of thermal and nuclear generators becomes 96 to 100% actually. As for the excess stability of turbine generators owing to the strengthening of transmission system and the adoption of super-high voltage, the demand of strict conditions can be dealt with by the adoption of super-fast response excitation system of thyristor shunt winding self exciting type. The adoption of the turbine generators with 90 to 95% power factor and the adoption of the thyristor shunt winding self exciting system were examined and evaluated. The rated power factor of generators, excitation system and economy of adopting these systems are explained. When the power factor of generators is increased from 0.9 to 0.95, about 6% of saving can be obtained in the installation cost. When the thyristor shunt winding self excitation is adopted, it is about 10% more economical than AC excitation. (Kako, I.)

  2. Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists.

    Science.gov (United States)

    Mochizuki, Michiyo; Kori, Masakuni; Kobayashi, Katsumi; Yano, Takahiko; Sako, Yuu; Tanaka, Maiko; Kanzaki, Naoyuki; Gyorkos, Albert C; Corrette, Christopher P; Cho, Suk Young; Pratt, Scott A; Aso, Kazuyoshi

    2016-03-24

    Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N(2)-(4-chloro-2-methoxy-6-methylphenyl)-1-methyl-N(7),N(7)-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 μM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 μmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research.

  3. Low Cardiorespiratory Fitness in African Americans: A Health Disparity Risk Factor?

    Science.gov (United States)

    Swift, Damon L.; Staiano, Amanda E.; Johannsen, Neil M.; Lavie, Carl J.; Earnest, Conrad P.; Katzmarzyk, Peter T.; Blair, Steven N.; Newton, Robert L.; Church, Timothy S.

    2013-01-01

    Low cardiorespiratory fitness (CRF) is a well-established risk factor for all-cause and cardiovascular disease mortality. African Americans have higher rates of cardiovascular disease compared to their Caucasian counterparts. However, the extent to which lower CRF levels contribute to the excess risk in African Americans has not been fully explored. The purpose of this review is to: 1) explore the literature evaluating the relationship between CRF and mortality specifically in African American populations; and 2) critically evaluate the studies which have compared CRF between African American and Caucasians in epidemiological studies and clinical trials. We have further discussed several potential mechanisms that may contribute to the observation of lower CRF levels in African American compared to Caucasian adults including potential racial differences in physical activity levels, muscle fiber type distribution, and hemoglobin levels. If lower CRF is generally present in African Americans compared to Caucasians, and is of a clinically meaningful difference, this may represent an important public health concern. PMID:23982718

  4. Maturity of hospital information systems: Most important influencing factors.

    Science.gov (United States)

    Vidal Carvalho, João; Rocha, Álvaro; Abreu, António

    2017-07-01

    Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.

  5. Computer Operating System Maintenance.

    Science.gov (United States)

    1982-06-01

    FACILITY The Computer Management Information Facility ( CMIF ) system was developed by Rapp Systems to fulfill the need at the CRF to record and report on...computer center resource usage and utilization. The foundation of the CMIF system is a System 2000 data base (CRFMGMT) which stores and permits access

  6. Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

    Directory of Open Access Journals (Sweden)

    Simon M Agwale

    Full Text Available Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G. Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G and consensus tat (CRF02_AG and G antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

  7. Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

    Science.gov (United States)

    Agwale, Simon M; Forbi, Joseph C; Notka, Frank; Wrin, Terri; Wild, Jens; Wagner, Ralf; Wolf, Hans

    2011-01-01

    Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA) to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G) and consensus tat (CRF02_AG and G) antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

  8. Focusing on the human factor in future expert systems

    International Nuclear Information System (INIS)

    Gordon, S.E.

    1987-01-01

    Technological advances in the area of artificial intelligence have produced expert systems that hold much promise for the design, operation, and maintenance of complex systems such as nuclear power plants. Such systems have been designed and implemented in a wide variety of task settings. In spite of the gains that have been made in the application of expert systems, there are still several difficult problems which have yet to be resolved. One of these problems is a frequently noted lack of user acceptance of newly fielded intelligent systems. This lack of acceptance can be attributed to a variety of factors, including unfamiliarity with computer technology, difficulty in adjusting to interface mechanisms, fear that the system was designed to replace the human operator, and a feeling that the human can perform the job better than the system. Some of the problems may be related to the fact that expert system design is essentially in it's infancy

  9. Status of human factors engineering system design in Europe

    International Nuclear Information System (INIS)

    Ives, G.

    1990-01-01

    A review of the European status of human factors engineering has been carried out covering a wide scope of activities which includes psychology, cognitive science, ergonomics, design, training, procedure writing, operating, artificial intelligence and expert systems. There is an increasing awareness of the part that human factors play in major nuclear power plant accidents. The emphasis of attention in human factors is changing. In some areas there are encouraging signs of progress and development, but in other areas there is still scope for improvement

  10. The exact wavefunction factorization of a vibronic coupling system

    International Nuclear Information System (INIS)

    Chiang, Ying-Chih; Klaiman, Shachar; Otto, Frank; Cederbaum, Lorenz S.

    2014-01-01

    We investigate the exact wavefunction as a single product of electronic and nuclear wavefunction for a model conical intersection system. Exact factorized spiky potentials and nodeless nuclear wavefunctions are found. The exact factorized potential preserves the symmetry breaking effect when the coupling mode is present. Additionally nodeless wavefunctions are found to be closely related to the adiabatic nuclear eigenfunctions. This phenomenon holds even for the regime where the non-adiabatic coupling is relevant, and sheds light on the relation between the exact wavefunction factorization and the adiabatic approximation

  11. Prognostic factors and scoring system for survival in colonic perforation.

    Science.gov (United States)

    Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

    2005-01-01

    No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

  12. FACTORS FOR THE IMPLEMENTATION OF CHANGE IN MANAGEMENT ACCOUNTING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Rodrigo Angonese

    2017-01-01

    Full Text Available This study aimed to analyze the motivating factors of the change process of the management accounting system, from the perspective of institutional theory. The research was classified as descriptive, qualitative, operationalized by explanatory case study. Data were collected through semi-structured interviews and analyzed using content analysis. The results show that in the analyzed case, the change in management accounting systems was motivated by a particular set of factors (improvisation and environmental social pressure, representative of internal and external pressures for organizations, each with its intensity.

  13. Favorable cardiovascular risk factor profile is associated with lower healthcare expenditure and resource utilization among adults with diabetes mellitus free of established cardiovascular disease: 2012 Medical Expenditure Panel Survey (MEPS).

    Science.gov (United States)

    Feldman, David I; Valero-Elizondo, Javier; Salami, Joseph A; Rana, Jamal S; Ogunmoroti, Oluseye; Osondu, Chukwuemeka U; Spatz, Erica S; Virani, Salim S; Blankstein, Ron; Blaha, Michael J; Veledar, Emir; Nasir, Khurram

    2017-03-01

    Given the prevalence and economic burden of diabetes mellitus (DM), we studied the impact of a favorable cardiovascular risk factor (CRF) profile on healthcare expenditures and resource utilization among individuals without cardiovascular disease (CVD), by DM status. 25,317 participants were categorized into 3 mutually-exclusive strata: "Poor", "Average" and "Optimal" CRF profiles (≥4, 2-3, 0-1 CRF, respectively). Two-part econometric models were utilized to study cost data. Mean age was 45 (48% male), with 54% having optimal, 39% average, and 7% poor CRF profiles. Individuals with DM were more likely to have poor CRF profile vs. those without DM (OR 7.7, 95% CI 6.4, 9.2). Individuals with DM/poor CRF profile had a mean annual expenditure of $9,006, compared to $6,461 among those with DM/optimal CRF profile (p profile is associated with significantly lower healthcare expenditures and utilization in CVD-free individuals across DM status, suggesting that these individuals require aggressive individualized prescriptions targeting lifestyle modifications and therapeutic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Numerical investigation on asymmetric bilayer system at integer filling factor

    Czech Academy of Sciences Publication Activity Database

    Nomura, K.; Yoshioka, D.; Jungwirth, Tomáš; MacDonald, A. H.

    2004-01-01

    Roč. 22, - (2004), s. 60-63 ISSN 1386-9477. [International Conference on Electronic Properties of Two-Dimensional Systems /15./. Nara, 14.07.2003-18.07.2003] Institutional research plan: CEZ:AV0Z1010914 Keywords : quantum Hall ferromagnet * asymmetric bilayer systems * anisotropy * stripe states Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.898, year: 2004

  15. Role of a genetic polymorphism in the corticotropin-releasing factor receptor 1 gene in alcohol drinking and seeking behaviors of Marchigian Sardinian alcohol-preferring (msP rats

    Directory of Open Access Journals (Sweden)

    Lydia Ojonemile Ayanwuyi

    2013-04-01

    Full Text Available Marchigian Sardinian alcohol-preferring (msP rats exhibit innate preference for alcohol, are highly sensitive to stress and stress-induced alcohol seeking. Genetic analysis showed that over-expression of the corticotropin-releasing factor (CRF system of msP rats is correlated with the presence of two single nucleotide polymorphisms (SNPs occurring in the promoter region (position -1836 and -2097 of the CRF1 receptor (CRF1-R gene. Here we examined whether these point mutations were associated to the innate alcohol preference, stress-induced drinking and seeking.We have recently re-derived the msP rats to obtain two distinct lines carrying the wild type (GG and the point mutations (AA, respectively. The phenotypic characteristics of these two lines were compared with those of unselected Wistar rats. Both AA and GG rats showed similar patterns of voluntary alcohol intake and preference. Similarly, the pharmacological stressor yohimbine (0.0, 0.625, 1.25 and 2.5 mg/kg elicited increased operant alcohol self-administration under fixed and progressive ratio reinforcement schedules in all three lines. Following extinction, yohimbine (0.0, 0.625, 1.25 and 2.5 mg/kg significantly reinstated alcohol seeking in the three groups. However, at the highest dose this effect was no longer evident in AA rats. Treatment with the CRF1-R antagonist antalarmin (0, 5, 10 and 20 mg/kg significantly reduced alcohol-reinforced lever pressing in the AA line (10 and 20 mg/kg while a weaker or no effect was observed in the Wistar and the GG group, respectively. Finally, antalarmin significantly reduced yohimbine-induced increase in alcohol drinking in all three groups.In conclusion, these specific SNPs in the CRF1-R gene do not seem to play a primary role in the expression of the msP excessive-drinking phenotype or stress-induced drinking but may be associated with a decreased threshold for stress-induced alcohol seeking and an increased sensitivity to the effects of

  16. Critical factors in the implementation process of integrated management systems

    Directory of Open Access Journals (Sweden)

    Ademir Antonio Ferreira

    2015-09-01

    Full Text Available This study is the result of research whose purpose was to study the implementation process of integrated management systems, called ERP Enterprise Resource Planning in the business environment. This study, more specifically, tried to identify the variables in this process and that, somehow, made it easy or caused some type of difficulty implementing the system. Based on the mixed method approach (Creswell, 2003, the study was performed by means of the content analysis of technical and scientific publications about this theme and by means of a field research for data collection from primary sources. The content analysis was based on the per mile procedure by Bardin (1977, making it possible to identify critical factors that may be found in the implementation of ERP system projects. Primary data was collected from structured interviews with the managers in charge of the implementation of the system, in each of the 12 companies in different sectors of the economy and based in Brazil. Based on this information, it was possible to test the factors extracted from the content analysis and then develop a list of factors that may effectively influence the implementation process of the system. In order to recognize the possible relations between the selected factors, the Spearman (rsp correlation coefficient was applied and the multiple regression analysis was performed by means of the stepwise procedure. The purpose of the regression analysis was to determine the relation of the “Assessment of the Implementation” dependent variable with other dependent variables in the selected categories. The results of these analyses showed that the support of the top management, the communication process for the clear evidence of this support, the technical support of the ERP program provider together with the project team expertise, training and qualification processes of the team in the system operation are significantly correlated and relevant factors for a

  17. Failure and factors of safety in piping system design

    International Nuclear Information System (INIS)

    Antaki, G.A.

    1993-01-01

    An important body of test and performance data on the behavior of piping systems has led to an ongoing reassessment of the code stress allowables and their safety margin. The codes stress allowables, and their factors of safety, are developed from limits on the incipient yield (for ductile materials), or incipient rupture (for brittle materials), of a test specimen loaded in simple tension. In this paper, we examine the failure theories introduced in the B31 and ASME III codes for piping and their inherent approximations compared to textbook failure theories. We summarize the evolution of factors of safety in ASME and B31 and point out that, for piping systems, it is appropriate to reconsider the concept and definition of factors of safety

  18. Memory systems, processes, and tasks: taxonomic clarification via factor analysis.

    Science.gov (United States)

    Bruss, Peter J; Mitchell, David B

    2009-01-01

    The nature of various memory systems was examined using factor analysis. We reanalyzed data from 11 memory tasks previously reported in Mitchell and Bruss (2003). Four well-defined factors emerged, closely resembling episodic and semantic memory and conceptual and perceptual implicit memory, in line with both memory systems and transfer-appropriate processing accounts. To explore taxonomic issues, we ran separate analyses on the implicit tasks. Using a cross-format manipulation (pictures vs. words), we identified 3 prototypical tasks. Word fragment completion and picture fragment identification tasks were "factor pure," tapping perceptual processes uniquely. Category exemplar generation revealed its conceptual nature, yielding both cross-format priming and a picture superiority effect. In contrast, word stem completion and picture naming were more complex, revealing attributes of both processes.

  19. System factors influencing utilisation of Research4Life databases by ...

    African Journals Online (AJOL)

    This is a comprehensive investigation of the influence of system factors on utilisation of Research4Life databases. It is part of a doctoral dissertation. Research4Life databases are new innovative technologies being investigated in a new context – utilisation by NARIs scientists for research. The study adopted the descriptive ...

  20. On Modeling and Analyzing Cost Factors in Information Systems Engineering

    NARCIS (Netherlands)

    Mutschler, B.B.; Reichert, M.U.

    Introducing enterprise information systems (EIS) is usually associated with high costs. It is therefore crucial to understand those factors that determine or influence these costs. Though software cost estimation has received considerable attention during the last decades, it is difficult to apply

  1. Factors affecting the choice of cropping systems in Kebbi State ...

    African Journals Online (AJOL)

    The study examined the factors that influence choice of cropping systems in Kebbi State Nigeria. The technique applied in the study was Logit regression. Data to conduct the research was obtained mainly from primary sources through a questionnaire survey of 256 farmers, comprising 98 monocroppers and 158 ...

  2. Relative contributions of individual, institutional and system factors ...

    African Journals Online (AJOL)

    This study investigated the relative contributions of individual, institutional and system factors to utilisation of Research4Life databases by scientists in the National Agricultural Research Institutes (NARIs) in Nigeria. The study adopted the descriptive survey research design of the correlational type. Simple and stratified ...

  3. A Systemic Approach to Implementing a Protective Factors Framework

    Science.gov (United States)

    Parsons, Beverly; Jessup, Patricia; Moore, Marah

    2014-01-01

    The leadership team of the national Quality Improvement Center on early Childhood ventured into the frontiers of deep change in social systems by funding four research projects. The purpose of the research projects was to learn about implementing a protective factors approach with the goal of reducing the likelihood of child abuse and neglect. In…

  4. A role for corticotropin-releasing factor signaling in the lateral habenula and its modulation by early-life stress.

    Science.gov (United States)

    Authement, Michael E; Langlois, Ludovic D; Shepard, Ryan D; Browne, Caroline A; Lucki, Irwin; Kassis, Haifa; Nugent, Fereshteh S

    2018-03-06

    Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb. Through its receptor CRFR1 and subsequently protein kinase A (PKA), CRF application increased the intrinsic excitability of LHb neurons by affecting changes in small-conductance SK-type and large-conductance BK-type K + channels. CRF also reduced inhibitory γ-aminobutyric acid-containing (GABAergic) synaptic transmission onto LHb neurons through endocannabinoid-mediated retrograde signaling. Maternal deprivation is a severe early-life stress that alters CRF neural circuitry and is likewise associated with abnormal mental health later in life. LHb neurons from pups deprived of maternal care exhibited increased intrinsic excitability, reduced GABAergic transmission, decreased abundance of SK2 channel protein, and increased activity of PKA, without any substantial changes in Crh or Crhr1 expression. Furthermore, maternal deprivation blunted the response of LHb neurons to subsequent, acute CRF exposure. Activating SK channels or inhibiting postsynaptic PKA activity prevented the effects of both CRF and maternal deprivation on LHb intrinsic excitability, thus identifying potential pharmacological targets to reverse central CRF circuit dysregulation in patients with associated disorders. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. The Impacts of System and Human Factors on Online Learning Systems Use and Learner Satisfaction

    Science.gov (United States)

    Alshare, Khaled A.; Freeze, Ronald D.; Lane, Peggy L.; Wen, H. Joseph

    2011-01-01

    Success in an online learning environment is tied to both human and system factors. This study illuminates the unique contributions of human factors (comfort with online learning, self-management of learning, and perceived Web self-efficacy) to online learning system success, which is measured in terms of usage and satisfaction. The research model…

  6. Human Factors Interface with Systems Engineering for NASA Human Spaceflights

    Science.gov (United States)

    Wong, Douglas T.

    2009-01-01

    This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

  7. Novel HIV-1 recombinants spreading across multiple risk groups in the United Kingdom: the identification and phylogeography of Circulating Recombinant Form (CRF 50_A1D.

    Directory of Open Access Journals (Sweden)

    Geraldine M Foster

    Full Text Available An increase in non-B HIV-1 infections among men who have sex with men (MSM in the United Kingdom (UK has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies.A total of 55,556 pol (reverse transcriptase and protease sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL. Overall 72 patients shared the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug users (IDUs. In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints, which has been classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST. This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a subtype B strain.We report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around 1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B. These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously

  8. Participatory ergonomics for psychological factors evaluation in work system design.

    Science.gov (United States)

    Wang, Lingyan; Lau, Henry Y K

    2012-01-01

    It is a well recognized understanding that workers whose voice needs to be heard should be actively encouraged as full participants and involved in the early design stages of new ergonomic work system which encompass the development and implementation of new tools, workplaces, technologies or organizations. This paper presents a novel participatory strategy to evaluate three key psychological factors which are respectively mental fatigue, spiritual stress, and emotional satisfaction in work system design based on a modified version of Participatory Ergonomics (PE). In specific, it integrates a PE technique with a formulation view by combining the parallel development of PE strategies, frameworks and functions throughout the coverage of the entire work system design process, so as to bridge the gap between qualitative and quantitative analysis of psychological factors which can cause adverse or advantageous effects on worker's physiological and behavioral performance.

  9. Object recognition in images via a factor graph model

    Science.gov (United States)

    He, Yong; Wang, Long; Wu, Zhaolin; Zhang, Haisu

    2018-04-01

    Object recognition in images suffered from huge search space and uncertain object profile. Recently, the Bag-of- Words methods are utilized to solve these problems, especially the 2-dimension CRF(Conditional Random Field) model. In this paper we suggest the method based on a general and flexible fact graph model, which can catch the long-range correlation in Bag-of-Words by constructing a network learning framework contrasted from lattice in CRF. Furthermore, we explore a parameter learning algorithm based on the gradient descent and Loopy Sum-Product algorithms for the factor graph model. Experimental results on Graz 02 dataset show that, the recognition performance of our method in precision and recall is better than a state-of-art method and the original CRF model, demonstrating the effectiveness of the proposed method.

  10. Enhanced metabolic effect of erythropoietin and keto acids in CRF patients on low-protein diet: Czech multicenter study.

    Science.gov (United States)

    Teplan, Vladimír; Schück, Otto; Knotek, Antonín; Hajný, Jan; Horácková, Miroslava; Kvapil, Milan

    2003-03-01

    Our study is designed to establish whether supplementation with erythropoietin (EPO) exerts additional beneficial metabolic effects in patients with chronic renal failure (CRF) treated with keto acids (KAs) on a low-protein diet (LPD). A long-term, prospective, randomized study was designed to use three therapeutic protocols: (A) EPO plus KAs plus LPD (group I), (B) EPO plus LPD (group II), and (C) LPD (group III). One hundred eighty-six randomly selected patients (90 men, 96 women; age, 22 to 78 years) with a creatinine clearance of 22 to 36 mL/min were monitored at the beginning and at every 6 months for 3 years. During the study period, glomerular filtration rate measured as inulin clearance decreased slightly (from 26.2 +/- 3.4 to 23.4 +/- 4.1 mL/min in group I), 27.4 +/- 4.8 to 20.2 +/- 4.4 mL/min in group II, and 26.8 +/- 3.6 to 17.4 +/- 4.1 mL/min in group III; P < 0.01). Serum urea levels also declined (P < 0.01), more pronouncedly in group I (P < 0.025). In group I, there was a significant increase in levels of leucine (P < 0.01) and albumin (P < 0.01) and a decrease in proteinuria (P < 0.01). Analysis of the lipid spectrum showed a mild, yet significant, decrease in total cholesterol and low-density lipoprotein cholesterol levels (P < 0.025), more pronounced in group I. In group I, there was a decrease in plasma triglyceride levels (from 362.85 +/- 115.05 mg/dL [4.1 +/- 1.3 mmol/L] to values as low as 203.55 +/- 70.80 mg/dL [2.3 +/- 0.8 mmol/L]; P < 0.01), whereas high-density lipoprotein cholesterol levels increased (from 34.75 +/- 7.72 mg/dL [0.9 +/- 0.2 mmol/L] to 46.33 +/- 7.72 mg/dL [1.2 +/- 0.2 mmol/L]; P < 0.025). Mean arterial blood pressure was stable. EPO supplementation in patients with CRF administered KAs potentiates the beneficial effects on metabolism of proteins, amino acids, and lipids. Long-term coadministration of EPO, KA, and LPD was associated with a delay in progression of renal failure and reduction in proteinuria.

  11. Challenges and Success Factors of ERP Systems in Australian SMEs

    Directory of Open Access Journals (Sweden)

    Sitalakshmi Venkatraman

    2016-05-01

    Full Text Available Today, great potential is envisaged for ERP systems in small and medium-sized enterprises (SMEs, and software vendors have been repackaging their ERP systems for SMEs with a recent focus on cloud-based systems. While cloud ERP offers the best solution for SMEs without the overheads of the huge investment and management costs that are associated with traditional ERP systems, the SME sector faces many challenges in their adoption. Traditional ERP studies have predominantly focused on large organizations, and gaps in the literature indicate that both vendor and consumer perspectives require more understanding with new technology offerings for SMEs. This paper describes some of the common challenges, such as cost effectiveness, alignment between software and business processes, customized governance and training, which form the major SME constraints for ERP system adoption. Due to the dynamic nature of SME businesses, best practice guidelines for an SME’s ERP implementation could be arrived at through closer investigation of its business requirements in order to avoid misfits. This forms the main objective of the study. We identify key success factors of ERP implementation in an Australian SME as a case study. These target success factors are then compared to the actual outcomes achieved. Factors such as business process alignment with the ERP system, meeting customer and stakeholder needs and reducing recurring and maintenance costs were key to the success of ERP implementation for the Australian SME. In particular, the IT and business strategy alignment with a customer focus and flexible reporting features of ERP systems has resulted in business agility.

  12. Decontamination factors of ceramic filter in radioactive waste incineration system

    International Nuclear Information System (INIS)

    Kanbe, Hiromi; Mayuzumi, Masami; Ono, Tetsuo; Yoshiki, Shinya; Kouyama, Hiroaki; Nagae, Madoka; Sekiguchi, Ryosaku; Takaoku, Yoshinobu; Hozumi, Masahiro.

    1987-01-01

    A suspension-firing type radioactive waste incineration system is developed and cold demonstration testing of ceramic filters for the system are carried out. The incineration system, which is useful for a wide variety of waste materials, can serve to simplify the facilities and to reduce the costs for waste disposal. The incineration system can be used for drying-processing of concentrated waste liquids and disposal of flame resistant materials including ion exchange resins and rubber, as well as for ordinary combustible solid materials. An on-line backwash system is adopted to allow the ceramic filters to operate stably for a long period of time. For one-step filtering using the ceramic filter, the decontamination factor is greater than 10 5 for the processing of various wastes. In a practical situation, there exist vapor produced by the spray drier and the cladding in used ion exchange resin, which act to increase the decontamination performance of the ceramic filters to ensure safe operation. For the waste incineration system equipped with a waste gas processing apparatus consisting of a ceramic filter and HEPA filter, the overall decontamination factor is expected to be greater than 10 6 at portions down to the outlet of the ceramic filter and greater than 10 8 at portions down to the outlet of the HEPA filter. (Nogami, K.)

  13. Risk factors for chronic renal failure in Ivory coast: A prospective study of 280 patients

    Directory of Open Access Journals (Sweden)

    Ackoundou-N′Guessan K

    2011-01-01

    Full Text Available Chronic renal failure (CRF represents the major cause of mortality in the nephro-logy unit in Ivory Coast because the means for appropriate management are lacking. The present study was performed to investigate the risk factors for CRF so that strategies for prevention could be elaborated. A case-control study was performed prospectively at the Yopougon Teaching Hos-pital in Abidjan from January 2006 to December 2006. Factors known to cause CRF were investigated in patients and controls. Their prevalence rates were compared with the general population. A total of 280 patients and 113 controls were recruited. The mean age of the patients was 37.88 ± 13.33 years and that of the controls was 41.5 ± 9.72 years. Both genders were equally represented. The main causes of CRF were chronic glomerulonephritis (47.48%, with HIV infec-tion accounting for 15% of them, and essential hypertension (HTA (25%. Essential HTA repre-sented the only factor which, if untreated, inevitably leads to CRF. Thus, our study indicates that HTA is a major public health concern. All efforts should be implemented to reduce the high prevalence of HTA and the deleterious effect of this disorder in Ivory Coast.

  14. Incomplete factorization technique for positive definite linear systems

    International Nuclear Information System (INIS)

    Manteuffel, T.A.

    1980-01-01

    This paper describes a technique for solving the large sparse symmetric linear systems that arise from the application of finite element methods. The technique combines an incomplete factorization method called the shifted incomplete Cholesky factorization with the method of generalized conjugate gradients. The shifted incomplete Cholesky factorization produces a splitting of the matrix A that is dependent upon a parameter α. It is shown that if A is positive definite, then there is some α for which this splitting is possible and that this splitting is at least as good as the Jacobi splitting. The method is shown to be more efficient on a set of test problems than either direct methods or explicit iteration schemes

  15. Nucleic acid amplification of HIV-1 integrase sequence subtypes CRF01_AE and B for development of HIV anti-integrase drug resistance genotyping assay

    Science.gov (United States)

    Adlar, F. R.; Bela, B.

    2017-08-01

    To anticipate the potential use of anti-integrase drugs in Indonesia for treatment of HIV-1 infection, the development of a drug resistance genotyping assay for anti-integrase is crucial in identifying the genetic drug resistance profile of Indonesian HIV-1 strains. This experiment aimed to amplify a target region in the integrase gene of Indonesian HIV-1 subtypes CRF01_AE and B that contain genetic mutations known to confer resistance to anti-integrase drug. Eleven archived plasma samples from individuals living with HIV-1 were obtained from the Virology and Cancer Pathobiology Research Center for Health Service (VCPRC FKUI-RSCM) laboratory. One of the plasma samples contained HIV-1 subtype B, and the remaining plasma samples contained subtype CRF01_AE. The target regions for all samples were amplified through RT-PCR, with an annealing temperature of 55 °C, using the primer pair AE_POL 4086F and AE_POL 5232R that were designed by VCPRC FKUI-RSCM. The results of this experiment show that 18.2% (2/11) of the samples were successfully amplified using the one-step RT-PCR. While the primer pair was effective in amplifying the target region in the integrase gene sequence for subtype B (100%; 1/1), it had a low efficacy (10%, 1/10) for subtype CRF01_AE. In conclusion, the primer pair can be used to amplify the target region in Indonesian HIV-1 strain subtypes CRF01_AE and B. However, optimization of the PCR condition and an increased number of samples would help to determine an accurate representation of the efficacy of the primer pair.

  16. Probing quantum frustrated systems via factorization of the ground state.

    Science.gov (United States)

    Giampaolo, Salvatore M; Adesso, Gerardo; Illuminati, Fabrizio

    2010-05-21

    The existence of definite orders in frustrated quantum systems is related rigorously to the occurrence of fully factorized ground states below a threshold value of the frustration. Ground-state separability thus provides a natural measure of frustration: strongly frustrated systems are those that cannot accommodate for classical-like solutions. The exact form of the factorized ground states and the critical frustration are determined for various classes of nonexactly solvable spin models with different spatial ranges of the interactions. For weak frustration, the existence of disentangling transitions determines the range of applicability of mean-field descriptions in biological and physical problems such as stochastic gene expression and the stability of long-period modulated structures.

  17. Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation

    Science.gov (United States)

    Liu, Xiaoqing; Xiu, Zhilong; Hao, Ce

    2009-05-01

    Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the major targets of anti-AIDS drug discovery. The circulating recombinant form 01 A/E (CRF01_AE, abbreviated AE) subtype is one of the most common HIV-1 subtypes, which is infecting more humans and is expanding rapidly throughout the world. It is, therefore, necessary to develop inhibitors against subtype AE HIV-1 PR. In this work, we have performed computer simulation of subtype AE HIV-1 PR with the drugs lopinavir (LPV) and nelfinavir (NFV), and examined the mechanism of resistance of the V82F mutation of this protease against LPV both structurally and energetically. The V82F mutation at the active site results in a conformational change of 79's loop region and displacement of LPV from its proper binding site, and these changes lead to rotation of the side-chains of residues D25 and I50'. Consequently, the conformation of the binding cavity is deformed asymmetrically and some interactions between PR and LPV are destroyed. Additionally, by comparing the interactive mechanisms of LPV and NFV with HIV-1 PR we discovered that the presence of a dodecahydroisoquinoline ring at the P1' subsite, a [2-(2,6-dimethylphenoxy)acetyl]amino group at the P2' subsite, and an N2 atom at the P2 subsite could improve the binding affinity of the drug with AE HIV-1 PR. These findings are helpful for promising drug design.

  18. Tools and technologies for expert systems: A human factors perspective

    Science.gov (United States)

    Rajaram, Navaratna S.

    1987-01-01

    It is widely recognized that technologies based on artificial intelligence (AI), especially expert systems, can make significant contributions to the productivity and effectiveness of operations of information and knowledge intensive organizations such as NASA. At the same time, these being relatively new technologies, there is the problem of transfering technology to key personnel of such organizations. The problems of examining the potential of expert systems and of technology transfer is addressed in the context of human factors applications. One of the topics of interest was the investigation of the potential use of expert system building tools, particularly NEXPERT as a technology transfer medium. Two basic conclusions were reached in this regard. First, NEXPERT is an excellent tool for rapid prototyping of experimental expert systems, but not ideal as a delivery vehicle. Therefore, it is not a substitute for general purpose system implementation languages such a LISP or C. This assertion probably holds for nearly all such tools on the market today. Second, an effective technology transfer mechanism is to formulate and implement expert systems for problems which members of the organization in question can relate to. For this purpose, the LIghting EnGineering Expert (LIEGE) was implemented using NEXPERT as the tool for technology transfer and to illustrate the value of expert systems to the activities of the Man-System Division.

  19. Selected equation of state in the acentric factor system

    International Nuclear Information System (INIS)

    Schreiber, D.R.; Pitzer, K.S.

    1988-06-01

    A new equation of state in the acentric factor system is developed on the basis of high-precision data. The region in critical temperature T/sub r/, critical density P/sub r/ space is identified where there is good agreement as well as the regions of significant departures. The equation fits very well in the critical region. 10 refs., 6 figs., 3 tabs

  20. Construction and characterisation of a full-length infectious molecular clone from a fast replicating, X4-tropic HIV-1 CRF02.AG primary isolate

    International Nuclear Information System (INIS)

    Tebit, Denis M.; Zekeng, Leopold; Kaptue, Lazare; Kraeusslich, Hans-Georg; Herchenroeder, Ottmar

    2003-01-01

    Based on our previous analysis of HIV-1 isolates from Cameroon, we constructed a full-length infectious molecular clone from a primary isolate belonging to the CRF02.AG group of recombinant viruses which dominate the HIV-epidemic in West and Central Africa. The virus derived by transfection of the proviral clone pBD6-15 replicated with similar efficiency compared to its parental isolate and used CXCR4 as coreceptor as well. Furthermore, HIV-1 BD6-15 exhibited similar replication properties and virus yield as the reference B-type HIV-1 strain NL4-3. Sequence analysis revealed open reading frames for all structural and accessory genes apart from vpr. Phylogenetic and bootscanning analyses confirmed that BD6-15 clusters with CRF02.AG recombinant strains from West and Central Africa with similar cross-over points as described for the CRF02.AG prototype strain lbNG. Thus, pBD6-15 represents the first non-subtype B infectious molecular clone of a fast replicating, high producer, X4-tropic primary HIV-1 isolate, which had only been briefly passaged in primary cells

  1. Short Communication Phylogenetic Characterization of HIV Type 1 CRF01_AE V3 Envelope Sequences in Pregnant Women in Northern Vietnam

    Science.gov (United States)

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca

    2012-01-01

    Abstract Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005–2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology. PMID:21936713

  2. The Cuban health care system and factors currently undermining it.

    Science.gov (United States)

    Nayeri, K

    1995-08-01

    This paper explores the dynamics of health and health care in Cuba during a period of severe crisis by placing it within its economic, social, and political context using a comparative historical approach. It outlines Cuban achievements in health care as a consequence of the socialist transformations since 1959, noting the full commitment by the Cuban state, the planned economy, mass participation, and a self-critical, working class perspective as crucial factors. The roles of two external factors, the U.S. economic embargo and the Council of Mutual Economic Cooperation (CMEA), are explored in shaping the Cuban society and economy, including its health care system. It is argued that the former has hindered health efforts in Cuba. The role of the latter is more complex. While the CMEA was an important source for economic growth, Cuban relations with the Soviet bloc had a damaging effect on the development of socialism in Cuba. The adoption of the Soviet model of economic development fostered bureaucracy and demoralization of Cuban workers. As such, it contributed to two internal factors that have undermined further social progress including in health care: low productivity of labor and the growth of bureaucracy. While the health care system is still consistently supported by public policy and its structure is sound, economic crisis undermines its material and moral foundations and threatens its achievements. The future of the current Cuban health care system is intertwined with the potentials for its socialist development.

  3. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    DEFF Research Database (Denmark)

    Bor, M V; Sørensen, B S; Vinter-Jensen, L

    2000-01-01

    BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

  4. Predicting survival function and identifying associated factors in patients with renal insufficiency in the metropolitan area of Maringá, Paraná State, Brazil.

    Science.gov (United States)

    Ramires, Thiago G; Nakamura, Luiz R; Righetto, Ana J; Ortega, Edwin M M; Cordeiro, Gauss M

    2018-02-05

    Renal insufficiency is a serious medical and public health problem worldwide. Recently, although many surveys have been developed to identify factors related to the lifetime of patients with renal insufficiency, controversial results from several studies suggest that researches should be conducted by region. Thus, in this study we aim to predict and identify factors associated with the lifetime of patients with chronic renal failure (CRF) in the metropolitan area of Maringá, Paraná State, Brazil, based on the generalized additive models for location, scale and shape (GAMLSS) framework. Data used in this study were collected from the Maringá Kidney Institute and comprehends 177 patients (classified with CRF and mostly being treated under the Brazilian Unified National Health System) enrolled in a hemodialysis program from 1978 up to 2010. By using this approach, we concluded that in other regions, gender, kidney transplant indicator, antibodies to hepatitis B and antibodies to hepatitis C are significant factors that affect the expected lifetime.

  5. Predicting survival function and identifying associated factors in patients with renal insufficiency in the metropolitan area of Maringá, Paraná State, Brazil

    Directory of Open Access Journals (Sweden)

    Thiago G. Ramires

    2018-02-01

    Full Text Available Renal insufficiency is a serious medical and public health problem worldwide. Recently, although many surveys have been developed to identify factors related to the lifetime of patients with renal insufficiency, controversial results from several studies suggest that researches should be conducted by region. Thus, in this study we aim to predict and identify factors associated with the lifetime of patients with chronic renal failure (CRF in the metropolitan area of Maringá, Paraná State, Brazil, based on the generalized additive models for location, scale and shape (GAMLSS framework. Data used in this study were collected from the Maringá Kidney Institute and comprehends 177 patients (classified with CRF and mostly being treated under the Brazilian Unified National Health System enrolled in a hemodialysis program from 1978 up to 2010. By using this approach, we concluded that in other regions, gender, kidney transplant indicator, antibodies to hepatitis B and antibodies to hepatitis C are significant factors that affect the expected lifetime.

  6. Insulin-Like Growth Factor (IGF System in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Agnieszka Adamek

    2018-04-01

    Full Text Available Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2 act in response to growth hormone (GH. Other IGF family components include at least six binding proteins (IGFBP1 to 6, manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R. The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth, and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD, lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma. Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.

  7. Enhanced/Synthetic Vision Systems - Human factors research and implications for future systems

    Science.gov (United States)

    Foyle, David C.; Ahumada, Albert J.; Larimer, James; Sweet, Barbara T.

    1992-01-01

    This paper reviews recent human factors research studies conducted in the Aerospace Human Factors Research Division at NASA Ames Research Center related to the development and usage of Enhanced or Synthetic Vision Systems. Research discussed includes studies of field of view (FOV), representational differences of infrared (IR) imagery, head-up display (HUD) symbology, HUD advanced concept designs, sensor fusion, and sensor/database fusion and evaluation. Implications for the design and usage of Enhanced or Synthetic Vision Systems are discussed.

  8. Human factors considerations for expert systems in the nuclear industry

    International Nuclear Information System (INIS)

    Nelson, W.R.

    1988-01-01

    This paper discusses the general human factors issues relative to the development and implementation of expert systems for the nuclear industry. It summarizes the relevant research that addresses these issues, and identifies those areas that need the most effort for success. Since much of the prominent work for the application of expert systems has focused on computerized aids for decision making in emergencies, this paper draws from this area for its examples. This area tends to highlight the issues because of the safety-critical nature of the application. The same issues, however, are relevant to other applications of expert systems in the nuclear industry as well, even though the consequences of failure may not be as dramatic

  9. Factors affecting economies of scale in combined sewer systems.

    Science.gov (United States)

    Maurer, Max; Wolfram, Martin; Anja, Herlyn

    2010-01-01

    A generic model is introduced that represents the combined sewer infrastructure of a settlement quantitatively. A catchment area module first calculates the length and size distribution of the required sewer pipes on the basis of rain patterns, housing densities and area size. These results are fed into the sewer-cost module in order to estimate the combined sewer costs of the entire catchment area. A detailed analysis of the relevant input parameters for Swiss settlements is used to identify the influence of size on costs. The simulation results confirm that an economy of scale exists for combined sewer systems. This is the result of two main opposing cost factors: (i) increased construction costs for larger sewer systems due to larger pipes and increased rain runoff in larger settlements, and (ii) lower costs due to higher population and building densities in larger towns. In Switzerland, the more or less organically grown settlement structures and limited land availability emphasise the second factor to show an apparent economy of scale. This modelling approach proved to be a powerful tool for understanding the underlying factors affecting the cost structure for water infrastructures.

  10. Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats

    International Nuclear Information System (INIS)

    Nakade, Yukiomi; Mantyh, C.; Pappas, T.N.; Takahashi, Toku

    2007-01-01

    Fecal pellet output has been assessed as a colonic motor activity because of its simplicity. However, it remains unclear whether an acceleration of colonic transit correlates well with an increase in fecal pellet output. We examined the causal relationship between colonic transit and fecal pellet output stimulated by the central application of corticotropin-releasing factor (CRF) and restraint stress. Immediately after intracisternal injection of CRF, 51 Cr was injected via a catheter positioned in the proximal colon. Ninety minutes after 51 Cr injection, the total number of excreted feces was counted, and then the rats were killed. The radioactivity of each colonic segment was evaluated, and the geometric center (GC) of the distribution of 51 Cr was calculated. For the restraint stress study, after administration of 51 Cr into the proximal colon, rats were submitted to wrapping restraint stress for 90 min. Then they were killed, and GC was calculated. Both restraint stress and CRF significantly accelerated colonic transit. There was a positive correlation observed between fecal pellet output and GC of colonic transit in response to restraint stress, but not CRF, when the number of excreted feces was more than three. In contrast, there was no significant correlation observed between the two in stress and CRF when the number of excreted feces was less than two. The acceleration of colonic transit in response to restraint stress and central administration of CRF does not always correlate with an increase in fecal pellet output. (author)

  11. Factors that Influence RF Breakdown in Antenna Systems

    Science.gov (United States)

    Caughman, J. B. O.; Baity, F. W.; Rasmussen, D. A.; Aghazarian, M.; Castano Giraldo, C. H.; Ruzic, David

    2007-11-01

    One of the main power-limiting factors in antenna systems is the maximum voltage that the antenna or vacuum transmission line can sustain before breaking down. The factors that influence RF breakdown are being studied in a resonant 1/4-wavelength section of vacuum transmission line terminated with an open circuit electrode structure. Breakdown can be initiated via electron emission by high electric fields and by plasma formation in the structure, depending on the gas pressure. Recent experiments have shown that a 1 kG magnetic field can influence plasma formation at pressures as low as 8x10-5 Torr at moderate voltage levels (LLC, for the U.S. Dept. of Energy under contract DE-AC05-00OR22725. Work supported by USDOE with grant DE-FG02-04ER54765

  12. Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Huang Xu

    2010-08-01

    Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

  13. DETERMINANT EROSION FACTORS FOR PENSION ROMANIAN SYSTEM - A STATISTICAL APPROACH

    Directory of Open Access Journals (Sweden)

    Ana-Gabriela BABUCEA

    2010-09-01

    Full Text Available The demographical evolutions of the last 20 years, the changes in the Romanian economy and society influenced one special category which is the retired people. As inactive population, retired people represents an important category, their numbers being rather big in comparison with the employed population, practical the contributors at the pensions fund. In 2010, the stat has serious problems with paying pensions. The evolution of this category of people is the subject of this paper. We try to identify the factors that had negative influence upon the pension Romanian system. The reference years that we considered are 1990-2009.

  14. High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

    Science.gov (United States)

    Kotaki, Tomohiro; Khairunisa, Siti Qamariyah; Sukartiningrum, Septhia Dwi; Arfijanto, M Vitanata; Utsumi, Takako; Normalina, Irine; Handajani, Retno; Widiyanti, Prihartini; Rusli, Musofa; Rahayu, Retno Pudji; Lusida, Maria Inge; Hayashi, Yoshitake; Nasronudin; Kameoka, Masanori

    2013-01-01

    Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs), we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1) and the prevalence of other blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus C (GBV-C), were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%). In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

  15. High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kotaki

    Full Text Available Human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs, we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs.The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1 and the prevalence of other blood-borne viruses, hepatitis B virus (HBV, hepatitis C virus (HCV and GB virus C (GBV-C, were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients.The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%. In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

  16. Assessment of the severity of asthma by an expert system. Description and evaluation.

    Science.gov (United States)

    Redier, H; Daures, J P; Michel, C; Proudhon, H; Vervloet, D; Charpin, D; Marsac, J; Dusser, D; Brambilla, C; Wallaert, B

    1995-02-01

    Asthmaexpert, an expert system (ES), was produced at the special request of several clinicians in order to better understand the medical decisions made clinical experts in managing an asthmatic patient. We describe and evaluate this knowledge base, focusing mainly on assessment of the severity of asthma. After compiling data from a patient, Asthmaexpert assesses the severity of the disease and identifies the trigger factors involved, suggests any further investigations that may be required, and offers a treatment strategy. Implemented with Nexpert and Hypercard, it runs on a MacIntosh personal computer. The validation stage involved eight clinical experts who provided 20 case report forms (CRF) with their conclusions about management of asthma. The CRF were then programmed into the ES, which provided its own conclusions about the same subjects. Afterward, all the experts evaluated the conclusions given by ES or by their colleagues in a double-blind manner. One hundred twenty-seven CRF were available. The reliability of the experts' opinions was good, with a substantial consensus between them when assessing severity scores (kappa = 0.27 to 0.54). There was no difference in concordance of opinions on severity scores either between the experts who designed the system and ES or between the other experts and ES (weighted kappa = 0.72 and 0.69, respectively). Experts judged that the severity scores given by ES were as good as those proposed by their colleagues, and that the overall conclusions given by ES were as good as or better than those given by their colleagues. The conclusions drawn by ES were given a good rating.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. THE INSPECTION LIKE QUALITY FACTOR IN THE EDUCATIONAL SYSTEM

    Directory of Open Access Journals (Sweden)

    Joaquín Oliver Pozo

    2016-07-01

    Full Text Available The Inspection, along with other educational sectors, shapes from complementarity, coordination and communication between them, the architecture of the educational system. Each has its specificity and its own space in Education. The aim of this study is simply identify and define the location of the inspection into the education system, between educational administration and schools, and the "why" (their mission, and consistent with it, "which makes" (its functions and assignations. Mission and functions that take place in schools, at the sight of the Educational Administration and the society, through the Inspectorate as organization. Of the principles underlying this organization and of the communication, training, and technical and professional exchange that drives through their organizational structures, will depend its leadership in Education and to be seen as a quality factor.

  18. Seismic analysis response factors and design margins of piping systems

    International Nuclear Information System (INIS)

    Shieh, L.C.; Tsai, N.C.; Yang, M.S.; Wong, W.L.

    1985-01-01

    The objective of the simplified methods project of the Seismic Safety Margins Research Program is to develop a simplified seismic risk methodology for general use. The goal is to reduce seismic PRA costs to roughly 60 man-months over a 6 to 8 month period, without compromising the quality of the product. To achieve the goal, it is necessary to simplify the calculational procedure of the seismic response. The response factor approach serves this purpose. The response factor relates the median level response to the design data. Through a literature survey, we identified the various seismic analysis methods adopted in the U.S. nuclear industry for the piping system. A series of seismic response calculations was performed. The response factors and their variabilities for each method of analysis were computed. A sensitivity study of the effect of piping damping, in-structure response spectra envelop method, and analysis method was conducted. In addition, design margins, which relate the best-estimate response to the design data, are also presented

  19. An Improved Reinforcement Learning System Using Affective Factors

    Directory of Open Access Journals (Sweden)

    Takashi Kuremoto

    2013-07-01

    Full Text Available As a powerful and intelligent machine learning method, reinforcement learning (RL has been widely used in many fields such as game theory, adaptive control, multi-agent system, nonlinear forecasting, and so on. The main contribution of this technique is its exploration and exploitation approaches to find the optimal solution or semi-optimal solution of goal-directed problems. However, when RL is applied to multi-agent systems (MASs, problems such as “curse of dimension”, “perceptual aliasing problem”, and uncertainty of the environment constitute high hurdles to RL. Meanwhile, although RL is inspired by behavioral psychology and reward/punishment from the environment is used, higher mental factors such as affects, emotions, and motivations are rarely adopted in the learning procedure of RL. In this paper, to challenge agents learning in MASs, we propose a computational motivation function, which adopts two principle affective factors “Arousal” and “Pleasure” of Russell’s circumplex model of affects, to improve the learning performance of a conventional RL algorithm named Q-learning (QL. Compared with the conventional QL, computer simulations of pursuit problems with static and dynamic preys were carried out, and the results showed that the proposed method results in agents having a faster and more stable learning performance.

  20. Radioautographic study of binding and internalization of corticotropin-releasing factor by rat anterior pituitary corticotrophs

    International Nuclear Information System (INIS)

    Leroux, P.; Pelletier, G.

    1984-01-01

    In order to identify the anterior pituitary cell type(s) containing corticotropin-releasing factor (CRF) receptors and to study the internalization processes of this peptide by the target cells, radioautography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after intracarotid injection of [ 125 I]iodo-CRF into intact and adrenalectomized female rats. In intact animals, all corticotrophs were labeled, whereas in the adrenalectomized animals about 80% of the hypertrophied corticotrophs (adrenalectomy cells) were. In control animals injected with both iodinated CRF and an excess of unlabeled peptide, no specific reaction could be detected. The time-course study in intact animals showed that 2 min after injection most silver grains were found over or within 160 nm of the plasma membrane. At the 5-min time intervals, grains were observed both over the plasma membrane and within the cytoplasm, associated with lysosomes, and the Golgi apparatus. Fifteen minutes after injection, grains were mostly found over lysosomes and the Golgi apparatus, whereas at the longest time intervals (30 and 60 min) almost no labeling could be detected. The results obtained in this study indicate that in the anterior pituitary CRF receptors are restricted to corticotrophs (as identified by electron microscopy) and that, after binding to the plasma membrane, CRF is rapidly internalized to Golgi elements and lysosomes

  1. Chart of conversion factors: From English to metric system and metric to English system

    Science.gov (United States)

    ,

    1976-01-01

    The conversion factors in the following tables are for conversion of our customary (English) units of measurement to SI*units, and for convenience, reciprocals are shown for converting SI units back to the English system. The first table contains rule-of-thumb figures, useful for "getting the feel" of SI units or mental estimation. The succeeding tables contain factors accurate to 3 or more significant figures. Please refer to known reference volumes for additional accuracy, as well as for factors dealing with other scientific notation involving SI units.

  2. Behavioral and physiological responses to central administration of corticotropin-releasing factor in the bluebanded goby (Lythrypnus dalli).

    Science.gov (United States)

    Solomon-Lane, Tessa K; Grober, Matthew S

    2012-07-16

    Central manipulation of neuromodulators is critical to establishing causal links between brain function and behavioral output. The absence of a rigorous method of evaluating intracerebroventricular (i.c.v.) injection efficacy in small model organisms is one reason why peripheral administration of neuroactive substances is more common. We use the bluebanded goby (Lythrypnus dalli), a small, highly social fish, to 1) validate our method of i.c.v. injection by testing the hypothesis that corticotropin-releasing factor (CRF) elevates ventilation rate (VR) and 2) propose a novel bioassay using basal physiology and behavior during recovery from anesthesia/i.c.v. administration to assess injection efficacy, neuromodulator activity, and procedural confounds. Central CRF administration significantly increased ventilation rate, demonstrating successful delivery of CRF to the brain. There were no significant differences in cortisol among treatments. The injection procedure did, however, decouple the temporal relationship between the initiation of ventilation and time to regain equilibrium present in control fish. Importantly, neither i.c.v. vehicle nor CRF injection affected the initiation of ventilation, disrupted the stereotyped recovery pattern following anesthesia, or initiated an endocrine stress response. Taken together, we suggest that 1) i.c.v. injection can be effectively used to manipulate central levels of CRF in L. dalli and 2) physiological and behavioral recovery from anesthesia may be used to evaluate injection/technique efficacy. We will use these data in future studies as a measure of effective CRF delivery, to allow for appropriate recovery from i.c.v. injection, and to better evaluate independent effects of CRF on social and/or sexual behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Design flow factors for sewerage systems in small arid communities

    Directory of Open Access Journals (Sweden)

    Emad H. Imam

    2014-09-01

    Full Text Available Reliable estimation of sewage flow rates is essential for the proper design of sewers, pumping stations, and treatment plants. The design of the various components of the sewerage system should be based on the most critical flow rates with a focus on extremely low and peak flow rates that would be sustained for a duration related to the acceptable limits of behavior of the components under consideration. The extreme flow conditions and to what extent they differ from the average values are closely related to the size of the community or network, and the socioeconomic conditions. A single pumping station is usually sufficient to pump flow from small community in either flat or non-undulating topography. Therefore, the hydraulic loading on the wastewater treatment plant (WWTP results from the pumped flow from the pumping station rather than the trunk sewer flow. The intermittent operation of the pumping units further accentuates the sewage hydrograph in the final trunk sewer. Accordingly, the design flow for the various components of the WWTP should be determined based on their relevant flow factors. In this study, analysis of one representative small community out of five monitored small communities in Egypt and the Kingdom of Saudi Arabia is presented. Pumped sewage flow rates were measured and the sewer incoming flows were hydraulically derived. The hourly and daily sewer and pumped flow records were analyzed to derive the relationship between the flow factors that would be sustained for various durations (instantaneously, 1 h, 2 h, etc. and their probability of non-exceedance. The resulting peaking factors with a consideration for their sustained flow duration and specified probability would permit the design of the various components of the treatment plant using more accurate critical flows.

  4. Design flow factors for sewerage systems in small arid communities.

    Science.gov (United States)

    Imam, Emad H; Elnakar, Haitham Y

    2014-09-01

    Reliable estimation of sewage flow rates is essential for the proper design of sewers, pumping stations, and treatment plants. The design of the various components of the sewerage system should be based on the most critical flow rates with a focus on extremely low and peak flow rates that would be sustained for a duration related to the acceptable limits of behavior of the components under consideration. The extreme flow conditions and to what extent they differ from the average values are closely related to the size of the community or network, and the socioeconomic conditions. A single pumping station is usually sufficient to pump flow from small community in either flat or non-undulating topography. Therefore, the hydraulic loading on the wastewater treatment plant (WWTP) results from the pumped flow from the pumping station rather than the trunk sewer flow. The intermittent operation of the pumping units further accentuates the sewage hydrograph in the final trunk sewer. Accordingly, the design flow for the various components of the WWTP should be determined based on their relevant flow factors. In this study, analysis of one representative small community out of five monitored small communities in Egypt and the Kingdom of Saudi Arabia is presented. Pumped sewage flow rates were measured and the sewer incoming flows were hydraulically derived. The hourly and daily sewer and pumped flow records were analyzed to derive the relationship between the flow factors that would be sustained for various durations (instantaneously, 1 h, 2 h, etc.) and their probability of non-exceedance. The resulting peaking factors with a consideration for their sustained flow duration and specified probability would permit the design of the various components of the treatment plant using more accurate critical flows.

  5. A systems biology approach to transcription factor binding site prediction.

    Directory of Open Access Journals (Sweden)

    Xiang Zhou

    2010-03-01

    Full Text Available The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates.We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data.Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct-interaction detection and TFBS-discovery accuracy. We estimated the accuracy

  6. Axiological crisis among the factors of development of political system

    Directory of Open Access Journals (Sweden)

    R. M. Kliuchnyk

    2015-12-01

    Full Text Available The article is dedicated to axiological crisis as one of the factors of development of political system. Intergeneration and civilization crises are separated. It is shown that contradictions between survival and self-expressionpolitical values often lead to political crises. The Arabic Spring is proved to have been a consequence of a deep generation crisis. Dangerous consequences of cultural and civilization crisis within globalization are underlined. The influence of illegal migration, extremism and intolerance on axiological crises is considered. A special attention is paid to modernization possibilities of high school within axiological crisis. The necessity of reforming of high school in order to avoid negative consequences of axiological crises is underlined. International experience in high school reforms is analyzed. The perspectives of its implementation in Ukraine are considered.

  7. Evolutionary History of HIV-1 Subtype B and CRF01_AE Transmission Clusters among Men Who Have Sex with Men (MSM) in Kuala Lumpur, Malaysia

    Science.gov (United States)

    Ng, Kim Tien; Ong, Lai Yee; Lim, Sin How; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253–3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2–7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion. PMID:23840653

  8. Evolutionary history of HIV-1 subtype B and CRF01_AE transmission clusters among men who have sex with men (MSM) in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Ng, Kim Tien; Ong, Lai Yee; Lim, Sin How; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253-3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2-7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion.

  9. Factors that influencing the usage of global distribution system

    Science.gov (United States)

    Budiasa, I. M.; Suparta, I. K.; Nadra, N. M.

    2018-01-01

    The advancement of Tourism is supported by Information and Communication Technology (ICT) innovation and changes. The use of GDS (Global Distribution System) i.e. Amadeus, Galileo, Sabre, and Worldspan in the tourism industry can increase the availability, frequency and speed of communication among the companies in providing services to potential tourists. This research is to investigate the factors that influence the actual use of GDS in the tourism industry especially travel agents, airlines and hotels in Bali. This research employed a mixed method of quantitative and qualitative approaches. Field surveys were conducted and 80 valid questionnaires were received and analyzed by using SPSS 17.0; descriptive, correlation, factor analysis and regression tests were conducted. The variables used are Perceived Ease of Use and Perceived Usefulness (Technology Acceptance Model); Awareness, Perceived Risk and Communication Channels are examined. This research revealed that Perceived Ease of Use, Perceived Usefulness, Awareness, and Communication Channels influence the Behavioural intention to use GDS, whereas Perceived Risk were found not significant influence the use of GDS. These findings enable travel agent, airline and hotel companies to make provision decision with respect to the actual use of GDS.

  10. Design of automatic power factor control system | Yanev | Botswana ...

    African Journals Online (AJOL)

    Maintenance of the proper power factor is a very important matter for the industry and for the economy of any country. A study of the power factor values for a number of industrial plants in Botswana shows that they operate at power-factors lower than the optimal values. If a plant power factor is different from its optimal value, ...

  11. SYSTEM OF THE FACTORS INFLUENCING LABOR PRODUCTIVITY IN IT FIRMS

    OpenAIRE

    Levon M. Seropov

    2015-01-01

    Internal and external factors, which influence labor productivity in IT companies, are considered. Internal factors are considered as fundamental factors, directlyinfluencing labor productivity. The analysismethod PESTL is adapted for fi nding out of external factors of labor productivity.

  12. RF system considerations for large high-duty-factor linacs

    International Nuclear Information System (INIS)

    Lynch, M.T.; Ziomek, C.D.; Tallerico, P.J.; Regan, A.H.; Eaton, L.; Lawrence, G.

    1994-01-01

    RF systems are often a major cost item for linacs, but this is especially true for large high-duty-factor linacs (up to and including CW) such as the Accelerator for Production of Tritium (APT) or the Accelerator for Transmutation of nuclear Waste (ATW). In addition, the high energy and high average beam current of these machines (approximately 1 GeV, 100--200 mA) leads to a need for excellent control of the accelerating fields in order to minimize the possibility of beam loss in the accelerator and the resulting activation. This paper will address the key considerations and limitations in the design of the RF system. These considerations impact the design of both the high power RF components and the RF controls. As might be expected, the two concerns sometimes lead to conflicting design requirements. For example minimum RF operating costs lead to a desire for operation near saturation of the high power RF generators in order to maximize the operating efficiency. Optimal control of the RF fields leads to a desire for maximum overdrive capability in those same generators in order to respond quickly to disturbances of the accelerator fields

  13. Cognitive and system factors contributing to diagnostic errors in radiology.

    Science.gov (United States)

    Lee, Cindy S; Nagy, Paul G; Weaver, Sallie J; Newman-Toker, David E

    2013-09-01

    In this article, we describe some of the cognitive and system-based sources of detection and interpretation errors in diagnostic radiology and discuss potential approaches to help reduce misdiagnoses. Every radiologist worries about missing a diagnosis or giving a false-positive reading. The retrospective error rate among radiologic examinations is approximately 30%, with real-time errors in daily radiology practice averaging 3-5%. Nearly 75% of all medical malpractice claims against radiologists are related to diagnostic errors. As medical reimbursement trends downward, radiologists attempt to compensate by undertaking additional responsibilities to increase productivity. The increased workload, rising quality expectations, cognitive biases, and poor system factors all contribute to diagnostic errors in radiology. Diagnostic errors are underrecognized and underappreciated in radiology practice. This is due to the inability to obtain reliable national estimates of the impact, the difficulty in evaluating effectiveness of potential interventions, and the poor response to systemwide solutions. Most of our clinical work is executed through type 1 processes to minimize cost, anxiety, and delay; however, type 1 processes are also vulnerable to errors. Instead of trying to completely eliminate cognitive shortcuts that serve us well most of the time, becoming aware of common biases and using metacognitive strategies to mitigate the effects have the potential to create sustainable improvement in diagnostic errors.

  14. Human factors measurement for future air traffic control systems.

    Science.gov (United States)

    Langan-Fox, Janice; Sankey, Michael J; Canty, James M

    2009-10-01

    This article provides a critical review of research pertaining to the measurement of human factors (HF) issues in current and future air traffic control (ATC). Growing worldwide air traffic demands call for a radical departure from current ATC systems. Future systems will have a fundamental impact on the roles and responsibilities of ATC officers (ATCOs). Valid and reliable methods of assessing HF issues associated with these changes, such as a potential increase (or decrease) in workload, are of utmost importance for advancing theory and for designing systems, procedures, and training. We outline major aviation changes and how these relate to five key HF issues in ATC. Measures are outlined, compared, and evaluated and are followed by guidelines for assessing these issues in the ATC domain. Recommendations for future research are presented. A review of the literature suggests that situational awareness and workload have been widely researched and assessed using a variety of measures, but researchers have neglected the areas of trust, stress, and boredom. We make recommendations for use of particular measures and the construction of new measures. It is predicted that, given the changing role of ATCOs and profound future airspace requirements and configurations, issues of stress, trust, and boredom will become more significant. Researchers should develop and/or refine existing measures of all five key HF issues to assess their impact on ATCO performance. Furthermore, these issues should be considered in a holistic manner. The current article provides an evaluation of research and measures used in HF research on ATC that will aid research and ATC measurement.

  15. Moving Towards Culturally Competent Health Systems: Organizational and Market Factors

    Science.gov (United States)

    Weech-Maldonado, Robert; Elliott, Marc; Pradhan, Rohit; Schiller, Cameron; Dreachslin, Janice; Hays, Ron D.

    2012-01-01

    Cultural competency has been proposed as an organizational strategy to address racial/ethnic disparities in the health care system; disparities are a long-standing policy challenge whose relevance is only increasing with the increasing population diversity of the US and across the world. Using an integrative conceptual framework based on the resource dependency and institutional theories, we examine the relationship between organizational and market factors and hospitals’ degree of cultural competency. Our sample consists of 119 hospitals located in the state of California (US) and is constructed using the following datasets for the year 2006: Cultural Competency Assessment Tool of Hospitals (CCATH) Survey, California’s Office of Statewide Health Planning & Development’s Hospital Inpatient Discharges and Annual Hospital Financial Data, American Hospital Association’s Annual Survey, and the Area Resource File. The dependent variable consists of the degree of hospital cultural competency, as assessed by the CCATH overall score. Organizational variables include ownership status, teaching hospital, payer mix, size, system membership, financial performance, and the proportion of inpatient racial/ethnic minorities. Market characteristics included hospital competition, the proportion of racial/ethnic minorities in the area, metropolitan area, and per capita income. Regression analyses were conducted to assess the relationship between the CCATH overall score and organizational and market variables. Our results show that hospitals which are not-for-profit, serve a more diverse inpatient population, and are located in more competitive and affluent markets exhibit a higher degree of cultural competency. Our results underscore the importance of both institutional and competitive market pressures in guiding hospital behavior. For instance, while not-for-profit may adopt innovative/progressive policies like cultural competency simply as a function of their organizational

  16. Moving towards culturally competent health systems: organizational and market factors.

    Science.gov (United States)

    Weech-Maldonado, Robert; Elliott, Marc N; Pradhan, Rohit; Schiller, Cameron; Dreachslin, Janice; Hays, Ron D

    2012-09-01

    Cultural competency has been proposed as an organizational strategy to address racial/ethnic disparities in the healthcare system; disparities are a long-standing policy challenge whose relevance is only increasing with the increasing population diversity of the US and across the world. Using an integrative conceptual framework based on the resource dependency and institutional theories, we examine the relationship between organizational and market factors and hospitals' degree of cultural competency. Our sample consists of 119 hospitals located in the state of California (US) and is constructed using the following datasets for the year 2006: Cultural Competency Assessment Tool of Hospitals (CCATH) Survey, California's Office of Statewide Health Planning & Development's Hospital Inpatient Discharges and Annual Hospital Financial Data, American Hospital Association's Annual Survey, and the Area Resource File. The dependent variable consists of the degree of hospital cultural competency, as assessed by the CCATH overall score. Organizational variables include ownership status, teaching hospital, payer mix, size, system membership, financial performance, and the proportion of inpatient racial/ethnic minorities. Market characteristics included hospital competition, the proportion of racial/ethnic minorities in the area, metropolitan area, and per capita income. Regression analyses were conducted to assess the relationship between the CCATH overall score and organizational and market variables. Our results show that hospitals which are not-for-profit, serve a more diverse inpatient population, and are located in more competitive and affluent markets exhibit a higher degree of cultural competency. Our results underscore the importance of both institutional and competitive market pressures in guiding hospital behavior. For instance, while not-for-profit may adopt innovative/progressive policies like cultural competency simply as a function of their organizational goals

  17. 75 FR 35093 - Civil Service Retirement System; Present Value Factors

    Science.gov (United States)

    2010-06-21

    ... present value factors to changes in demographic factors adopted by the Board of Actuaries of the Civil... actuarial assumptions and data to the Board of Actuaries, care of Gregory Kissel, Actuary, Office of... 1986, Public Law 99- 335, based on changed demographic factors adopted by the Board of Actuaries of the...

  18. 21 CFR 864.7280 - Factor V Leiden DNA mutation detection systems.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Factor V Leiden DNA mutation detection systems....7280 Factor V Leiden DNA mutation detection systems. (a) Identification. Factor V Leiden deoxyribonucleic acid (DNA) mutation detection systems are devices that consist of different reagents and...

  19. Cardiovascular risk factors in cognitively impaired nursing home patients: A relationship with pain?

    NARCIS (Netherlands)

    Achterberg, W.P.; Scherder, E.J.A.; Pot, A.M.; Ribbe, M.W.

    2007-01-01

    Cardiovascular risk factors (CRF) such as hypertension and diabetes mellitus favour the development of both vascular dementia (VaD) and Alzheimer’s disease (AD). The resulting deafferentation may increase the experience of pain in VaD and in AD. The goal of the present study was to examine the

  20. Socializing the human factors analysis and classification system: incorporating social psychological phenomena into a human factors error classification system.

    Science.gov (United States)

    Paletz, Susannah B F; Bearman, Christopher; Orasanu, Judith; Holbrook, Jon

    2009-08-01

    The presence of social psychological pressures on pilot decision making was assessed using qualitative analyses of critical incident interviews. Social psychological phenomena have long been known to influence attitudes and behavior but have not been highlighted in accident investigation models. Using a critical incident method, 28 pilots who flew in Alaska were interviewed. The participants were asked to describe a situation involving weather when they were pilot in command and found their skills challenged. They were asked to describe the incident in detail but were not explicitly asked to identify social pressures. Pressures were extracted from transcripts in a bottom-up manner and then clustered into themes. Of the 28 pilots, 16 described social psychological pressures on their decision making, specifically, informational social influence, the foot-in-the-door persuasion technique, normalization of deviance, and impression management and self-consistency motives. We believe accident and incident investigations can benefit from explicit inclusion of common social psychological pressures. We recommend specific ways of incorporating these pressures into theHuman Factors Analysis and Classification System.

  1. Modified Framingham Risk Factor Score for Systemic Lupus Erythematosus.

    Science.gov (United States)

    Urowitz, Murray B; Ibañez, Dominique; Su, Jiandong; Gladman, Dafna D

    2016-05-01

    The traditional Framingham Risk Factor Score (FRS) underestimates the risk for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We aimed to determine whether an adjustment to the FRS would more accurately reflect the higher prevalence of CAD among patients with SLE. Patients with SLE without a previous history of CAD or diabetes followed regularly at the University of Toronto Lupus Clinic were included. A modified FRS (mFRS) was calculated by multiplying the items by 1.5, 2, 3, or 4. In the first part of the study, using one-third of all eligible patients, we evaluated the sensitivity and specificity of the FRS and the different multipliers for the mFRS. In the second part of the study, using the remaining 2/3 of the eligible patients, we compared the predictive ability of the FRS to the mFRS. In the third part of the study, we assessed the prediction for CAD in a time-dependent analysis of the FRS and mFRS. There were 905 women (89.3%) with a total of 95 CAD events included. In part 1, we determined that a multiplier of 2 provided the best combination of sensitivity and specificity. In part 2, 2.4% of the patients were classified as moderate/high risk based on the classic FRS and 17.3% using the 2FRS (the FRS with a multiplier of 2). In part 3, a time-dependent covariate analysis for the prediction of the first CAD event revealed an HR of 3.22 (p = 0.07) for the classic FRS and 4.37 (p mFRS in which each item is multiplied by 2 more accurately predicts CAD in patients with SLE.

  2. Use of physical activity and cardiorespiratory fitness in identifying cardiovascular risk factors in male brazilian adolescents

    Directory of Open Access Journals (Sweden)

    Lilian Messias Sampaio Brito

    2016-02-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n6p678   The aim of this study was to investigate the impact of physical activity (PA and cardiorespiratory fitness (CRF levels on the prevalence of overweight and high blood pressure levels in adolescents. In this observational, cross-sectional study, 614 boys aged 10-14 years were assessed for height, body mass, body mass index (BMI, waist circumference (WC and blood pressure (BP. CRF was assessed using a run test (Léger Test and subjects were then grouped according to their CRF level. PA level was assessed through a questionnaire (The Three Day Physical Activity Recall and classified into two groups, namely > 300 minutes of PA/week and < 300 minutes of PA/week. Maturational stage was evaluated according to the development of pubic hair (self-assessment as proposed by Tanner. We used statistical descriptive analysis, univariate and multivariate analyses in the total participants and subjects were divided by age. Fifty percent of the sample performed < 300 minutes of PA/week and 67.6% had unsatisfactory CRF levels. There was a higher prevalence of unsatisfactory CRF levels among subjects with altered BMI (overweight, WC (abdominal obesity or BP (high blood pressure for all age groups. PA history, however, did not show any significance. A total of 31% of participants were overweight, 24.8% had abdominal obesity and 15.4% had increased BP. Unsatisfactory CRF levels were found to be a better predictor for the diagnosis of cardiovascular diseases (CV risk factors than PA history, regardless of age group.

  3. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization.

    Science.gov (United States)

    Gully, Danielle; Geslin, Michel; Serva, Laurence; Fontaine, Evelyne; Roger, Pierre; Lair, Christine; Darre, Valerie; Marcy, Claudine; Rouby, Pierre-Eric; Simiand, Jacques; Guitard, Josette; Gout, Georgette; Steinberg, Regis; Rodier, Daniel; Griebel, Guy; Soubrie, Philippe; Pascal, Marc; Pruss, Rebecca; Scatton, Bernard; Maffrand, Jean-Pierre; Le Fur, Gerard

    2002-04-01

    4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1- (3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A), a new 2-aminothiazole derivative, shows nanomolar affinity for human cloned or native corticotrophin-releasing factor (CRF)(1) receptors (pK(i) values of 8.73 and 9.08, respectively), and a 1000-fold selectivity for CRF(1) versus CRF(2 alpha) receptor and CRF binding protein. SSR125543A antagonizes CRF-induced stimulation of cAMP synthesis in human retinoblastoma Y 79 cells (IC(50) = 3.0 +/- 0.4 nM) and adrenocorticotropin hormone (ACTH) secretion in mouse pituitary tumor AtT-20 cells. SSR125543A is devoid of agonist activity in these models. Its brain penetration was demonstrated in rats by using an ex vivo [(125)I-Tyr(0)] ovine CRF binding assay. SSR125543A displaced radioligand binding to the CRF(1) receptor in the brain with an ID(50) of 6.5 mg/kg p.o. (duration of action >24 h). SSR125543A also inhibited the increase in plasma ACTH levels elicited in rats by i.v. CRF (4 microg/kg) injection (ID(50) = 1, 5, or 5 mg/kg i.v., i.p., and p.o., respectively); this effect lasted for more than 6 h when the drug was given orally at a dose of 30 mg/kg. SSR125543A (10 mg/kg p.o.) reduced by 73% the increase in plasma ACTH levels elicited by a 15-min restraint stress in rats. Moreover, SSR125543A (20 mg/kg i.p.) also antagonized the increase of hippocampal acetylcholine release induced by i.c.v. injection of 1 microg of CRF in rats. Finally, SSR125543A reduced forepaw treading induced by i.c.v. injection of 1 microg of CRF in gerbils (ID(50) = approximately 10 mg/kg p.o.). Altogether, these data indicate that SSR125543A is a potent, selective, and orally active CRF(1) receptor antagonist.

  4. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous

  5. Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health

    Directory of Open Access Journals (Sweden)

    Donny eJanssen

    2013-03-01

    Full Text Available Physiological responses to stress coordinated by the hypothalamo-pituitary-adrenal (HPA- axis are concerned with maintaining homeostasis in the presence of real or perceived challenges. Regulators of this axis are corticotrophin releasing hormone (CRF and CRF related neuropeptides, including urocortins (Ucn 1, 2 and 3. They mediate their actions by binding to CRF receptors (CRFR 1 and 2, which are located in several stress related brain regions. The prevailing theory has been that the initiation of and the recovery from an elicited stress response is coordinated by two elements, viz. the (mainly opposing, but well balanced actions of CRFR1 and CRFR2. Such a dualistic view suggests that CRF/CRFR1 controls the initiation of, and urocortins/CRFR2 mediate the recovery from stress to maintain body and mental health. Consequently, failed adaptation to stress can lead to neuropathology, including anxiety and depression. Recent literature, however, challenges such dualistic and complementary actions of CRFR1 and CRFR2, and suggests that stress recruits CRF system components in a brain area and neuron specific manner to promote adaptation as conditions dictate.

  6. Characterization of a Cytokinin Response Factor in Arabidopsis thaliana

    OpenAIRE

    Ketelsen, Bernd

    2012-01-01

    The papers of this thesis are not available in Munin: 1. Bernd Ketelsen, Rainer Schwacke, Kirsten Krause and Karsten Fischer: 'Transcriptional activation by Cytokinin Response Factor 5 is governed by an acidic Cterminus containing two conserved domains' (manuscript) 2. Bernd Ketelsen, Stian Olsen, Kirsten Krause and Karsten Fischer: 'Cytokinin responsive factor 5 (CRF5) is involved in root development, hormonal crosstalk and sugar metabolism in Arabidopsis thaliana' (manuscript) 3. Bernd K...

  7. Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

    Science.gov (United States)

    Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

    2012-01-01

    Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

  8. The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

    DEFF Research Database (Denmark)

    Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

    2017-01-01

    BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain...... fitness (CRF), anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were...

  9. Analytical static structure factor for a two-component system ...

    Indian Academy of Sciences (India)

    Marwan Al-Raeei

    2018-03-29

    Mar 29, 2018 ... be useful in studying biomolecular fluids and other soft matter fluids. Keywords. Ornstein–Zernike ... partial structure factor; isothermal compressibility; soft matter. PACS No. 05.20.Jj. 1. ..... computing. Users need to have ...

  10. Nitrification in Chloraminated Drinking Water Distribution Systems: Factors Affecting Occurrence

    Science.gov (United States)

    Drinking water distribution systems with ammonia present from either naturally occurring ammonia or ammonia addition during chloramination are at risk for nitrification. Nitrification in drinking water distribution systems is undesirable and may result in water quality degradatio...

  11. 76 FR 55213 - Technical Amendments to Federal Employees' Retirement System; Present Value Conversion Factors...

    Science.gov (United States)

    2011-09-07

    ... Employees' Retirement System; Present Value Conversion Factors for Spouses of Deceased Separated Employees... to read as follows: Appendix A to Subpart C of Part 843--Present Value Conversion Factors for Earlier...

  12. Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

    NARCIS (Netherlands)

    Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

    2008-01-01

    This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

  13. Contextual Factors Impacting Battered Women's Intentions to Reuse the Criminal Legal System

    Science.gov (United States)

    Fleury-Steiner, Ruth E.; Bybee, Deborah; Sullivan, Cris M.; Belknap, Joanne; Melton, Heather C.

    2006-01-01

    While a small number of past studies have examined either situational, relational, or systems-level factors that influence battered women's use of either the police, prosecutorial, or court systems, no study to date has examined how these factors each influence women's intentions to reuse these systems. To address this gap, in-person interviews…

  14. A physical review on power system reliability factors

    International Nuclear Information System (INIS)

    Navid, Taghizadegan; Ahmad Reza, Zentabchi; Mohammad Ali, Tavakoli; Nader, Samsunchi; Mohammad Ali, Tavakoli

    2005-01-01

    Full text : Planning and design engineers and management must necessarily take into consideration the funds available, the requirements of regulatory agencies and other restrictions that may be imposed, as well as availability of equipment and supplies. A well-designed electrical power system strikes a reasonable between reliability and cost. A prime responsibility of power system operators is to operate their systems in such a way that will provide the maximum reliability of service possible with the facilities under their control

  15. An assay system for factors involved in mammalian DNA replication

    International Nuclear Information System (INIS)

    Reinhard, P.; Maillart, P.; Schluchter, M.; Gautschi, J.R.; Schindler, R.

    1979-01-01

    An assay for cellular factors stimulating DNA synthesis by partially lysed CHO cells is presented. The assay is based on the observation that in highly lysed cells, DNA synthesis, as determined by [ 3 H]dTTP incorporation, was only 2-5% of that in gently lysed cells, and that this low level of DNA synthesis could be increased by a factor of approx. 50 by the addition of CHO cell extract (i.e. supernatant of a cell homogenate subjected to high-speed centrifugation.) (Auth.)

  16. Risk group characteristics and viral transmission clusters in South-East Asian patients infected with HIV-1 circulating recombinant form (CRF)01_AE and subtype B

    Science.gov (United States)

    Oyomopito, Rebecca A; Chen, Yen-Ju; Sungkanuparph, Somnuek; Kantor, Rami; Merati, Tuti; Yam, Wing-Cheong; Sirisanthana, Thira; Li, Patrick CK; Kantipong, Pacharee; Phanuphak, Praphan; Lee, Chris KC; Kamarulzaman, Adeeba; Ditangco, Rossana; Huang, Szu-Wei; Sohn, Annette H; Law, Matthew; Chen, Yi Ming A

    2016-01-01

    HIV-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF)01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multi-centre prospective cohort of HIV-infected patients. Associations between HIV-exposure, patient gender, country of sample origin and HIV-1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of males within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p Malaysia: 47.8%, Philippines: 25.0%; p <0.001). After adjustment, we found increased subtype B infection among men-who-have-sex with-men, relative to heterosexual-reported exposures (OR = 2.4, p <0.001). We further describe four transmission clusters of 8–15 treatment naive, predominantly symptomatic patients (two each for subtype B and CRF01_AE). Risk-group sub-populations differed with respect to the infecting HIV-1 genotype. Homosexual exposure patients had a higher odds of being infected with subtype B. Where HIV-1 genotypes circulate within countries or patient risk-groups, local monitoring of genotype-specific transmissions may play a role in focussing public health prevention strategies. Phylogenetic evaluations provide complementary information for surveillance and monitoring of viruses with high mutation rates such as HIV-1 and Ebola. PMID:26362956

  17. The future of intelligent manufacturing systems and human factors

    NARCIS (Netherlands)

    Vink, P.; Stahre, J.

    2006-01-01

    In this paper the results of a 3 year European project are described. In this project 20 experts in the field of human factors define the most promising way of using the European work force in manufacturing in the future. Based on discussions between the experts and participating companies and

  18. Determination of seismic performance factors for CLT shear wall systems

    Science.gov (United States)

    M. Omar Amini; John W. van de Lindt; Douglas Rammer; Shiling Pei; Philip Line; Marjan Popovski

    2016-01-01

    This paper presents selected results of connector testing and wall testing which were part of a Forest Products Lab-funded project undertaken at Colorado State University in an effort to determine seismic performance factors for cross laminated timber (CLT) shear walls in the United States. Archetype development, which is required as part of the process, is also...

  19. Evaluating medical and systemic factors related to maternal and ...

    African Journals Online (AJOL)

    Background: This study examined maternal morbidity and mortality and neonatal mortality over a multi-year period from de-identified retrospective medical records at Nyakahanga Designated District Hospital in north-western Tanzania. The study aimed to examine factors related to maternal mortality (MMR) and morbidity in ...

  20. THE SUSTAINABILITY FACTOR AND THE SPANISH PUBLIC PENSION SYSTEM

    Directory of Open Access Journals (Sweden)

    Alicia de las Heras Camino

    2014-05-01

    Full Text Available The sustainability factor is a tool for which the main goal is to contribute to the solvency of Social Security. In Spain, it has been articulated by a Sustainability factor, based on a life expectancy ratio, and a Pension Revaluation Index that replaces the Consumer Price Index for revaluation. However, as outlined in this article, the alternatives chosen are not exempt from uncertainty in their practical application nor are they the only possibility of action. El factor de sostenibilidad es una herramienta cuyo objetivo prioritario es contribuir a la solvencia de la Seguridad Social. En España se ha articulado mediante un Factor de sostenibilidad basado en el cociente de esperanzas de vida y un Índice de revalorización de pensiones que sustituye en dicha revalorización al Índice de Precios al Consumo. Sin embargo, tal y como se expone en este artículo, las alternativas escogidas no están exentas de incertidumbre en su aplicación práctica ni son la única posibilidad de acción.

  1. Factors affecting the utilisation of electronic medical records system ...

    African Journals Online (AJOL)

    Malawi Medical Journal 29 (3): September 2017. Electronic medical ... care, as they enable storage of large amounts of data and ... EMRs. This study assessed factors that affect the use of EMRs in Malawi, particularly at Queen Elizabeth and Kamuzu Central ..... paperless hospitals in Norway : A socio-technical perspective.

  2. PERIODONTAL INFECTIONS AS A RISK FACTOR FOR VARIOUS SYSTEMIC DISEASES

    OpenAIRE

    Solanki, Gaurav; Solanki, Renu

    2012-01-01

    A healthy periodontium is needed for the general well being of an individual. However, periodontal diseases are common and periodontal infections are increasingly associated with systemic diseases. The literature is focused on the association between periodontal infections and systemic diseases. The individuals with periodontal disease may be at higher risk for adverse medical outcomes including cardiovascular diseases, respiratory infections, adverse pregnancy outcomes, rheumatoid arthritis ...

  3. Morphology of Design of Aerospace Systems with Inclusion of Human Factors

    Science.gov (United States)

    1977-08-01

    Visual Indicators," Human Factors, 1971, 13(5), pp. 427-433. 22. Mayer, Sylvia R., "Trends in Human Factors Research for Military Information Systems...34The Standardi- zation of Human Factors Data," Human Factors, 1970, 12(1), pp. 55-62. 29. Plath , D.W., "Th’ Readability of Segmented and Con... Sylvia R., "Trends in Human Factors Research for Military Information Systems," Human Factors, 1970, 12(2), pp. 177-186. 35. Meister, David, Dennis 3

  4. Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF, and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system

    Directory of Open Access Journals (Sweden)

    Aloe Luigi

    2003-04-01

    Full Text Available Abstract Previous studies on the effect of repeated electro-acupuncture (EA treatments in rats with steriod-induced polycystic ovaries (PCO, EA has been shown to modulate nerve growth factor (NGF concentration in the ovaries as well as corticotropin releasing factor (CRF in the median eminence (ME. In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1, a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p p p p

  5. Behavioral Risk Factor Surveillance System (BRFSS) Historical Questions

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1984-2016. Centers for Disease Control and Prevention (CDC). BRFSS Survey Data. The BRFSS is a continuous, state-based surveillance system that collects information...

  6. Noise factor of a high-speed cinematography system

    International Nuclear Information System (INIS)

    Secroun, A.

    2000-01-01

    Inertial confinement fusion simulates in a laboratory the thermodynamic state of the center of stars, thus leading to the determination of stellar parameters. In order to reach that aim, high-speed cinematography brings up instruments specifically adapted to picosecond measurement, for which it is necessary to know the final precision. A model of the noise factor of the instruments under study is introduced and confronted to the experimental results obtained. (authors)

  7. Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

    Science.gov (United States)

    Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

    2011-05-01

    Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat.

    Directory of Open Access Journals (Sweden)

    Linda Sterrenburg

    Full Text Available BACKGROUND: Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS after which immediate early gene products, corticotropin-releasing factor (CRF mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN, oval (BSTov and fusiform (BSTfu parts of the bed nucleus of the stria terminalis, and central amygdala (CeA. RESULTS: CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.

  9. Power profiling of Cholesky and QR factorizations on distributed memory systems

    KAUST Repository

    Bosilca, George; Ltaief, Hatem; Dongarra, Jack

    2012-01-01

    with a dynamic distributed scheduler (DAGuE) to leverage distributed memory systems. We present performance results (Gflop/s) as well as the power profile (Watts) of two common dense factorizations needed to solve linear systems of equations, namely

  10. Human performance modeling for system of systems analytics: combat performance-shaping factors.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Miller, Dwight Peter

    2006-01-01

    The US military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives. To support this goal, Sandia National Laboratories (SNL) has undertaken a program of HPM as an integral augmentation to its system-of-system (SoS) analytics capabilities. The previous effort, reported in SAND2005-6569, evaluated the effects of soldier cognitive fatigue on SoS performance. The current effort began with a very broad survey of any performance-shaping factors (PSFs) that also might affect soldiers performance in combat situations. The work included consideration of three different approaches to cognition modeling and how appropriate they would be for application to SoS analytics. This bulk of this report categorizes 47 PSFs into three groups (internal, external, and task-related) and provides brief descriptions of how each affects combat performance, according to the literature. The PSFs were then assembled into a matrix with 22 representative military tasks and assigned one of four levels of estimated negative impact on task performance, based on the literature. Blank versions of the matrix were then sent to two ex-military subject-matter experts to be filled out based on their personal experiences. Data analysis was performed to identify the consensus most influential PSFs. Results indicate that combat-related injury, cognitive fatigue, inadequate training, physical fatigue, thirst, stress, poor perceptual processing, and presence of chemical agents are among the PSFs with the most negative impact on combat performance.

  11. Practical Consideration Factors to Design Array Configuration of Direction Finding System for Airborne Signal Intelligence

    Directory of Open Access Journals (Sweden)

    Jong-Hwan Lee

    2018-01-01

    Full Text Available Airborne signal intelligence (SIGINT systems must be capable of locating radio signal sources. Direction finding (DF to support this capability is an important factor. There are some practical considerations to be taken when designing the array configuration of a DF system for airborne SIGINT systems. This paper summarizes the practical factors when designing the array configuration of the DF system for airborne SIGINT. In particular, it focuses on four areas: antenna consideration factors when installing the DF system for airborne SIGINT from a practical point of view, array configuration methods for airborne communications intelligence and electronic intelligence, and a numerical analysis to select the optimum antenna position for airborne SIGINT.

  12. Control of the renal renin system by local factors

    DEFF Research Database (Denmark)

    Wagner, C; Jensen, B L; Krämer, B K

    1998-01-01

    prostanoid, both stimulate renin secretion and renin gene expression by activating cAMP formation in JG cells. Although the direct effect of NO on JG cells is less clear, its overall effect in vivo seems to be to stimulate the renin system. Evidence is emerging that stimulation by NO is related to the c......AMP pathway, and cGMP-induced inhibition of cAMP-phosphodiesterase III (PDE-III) may mediate this effect. ETs, on the other hand, appear to inhibit the renin system, in particular in those pathways activated by cAMP, acting via Ca2+- and protein kinase C-related mechanisms. There is increasing evidence...... that both NO and PGs could be involved in the physiological regulatory mechanisms by which salt intake affects the renin system....

  13. Evolution of the global energy system: technology and other factors

    Energy Technology Data Exchange (ETDEWEB)

    de Leone, R.

    Future directions in government energy policies are assessed in light of the energy evolution following the 1973 oil crisis and the impacts created by technology transfer and other factors. In particular, the paper examines changes which are occurring in global marketing and commercialization trends, and in public opinion, especially in response to the techniques employed by planners in assessing new energy sources and technologies designed to lessen dependency on oil imports. It is noted that greater consideration must be given by scientists and engineers to the socio-economic impacts of their research efforts.

  14. Factors that influence the acceptance of integrated community energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A. S.; Tschanz, J. F.; Mosena, D.; Erley, D.; Gil, E.; Slovak, P.; Lenth, C. S.

    1977-01-01

    This report is part of a series of studies designed to analyze the commercialization potential of various concepts of community-scale energy systems that have been termed Integrated Community Energy Systems (ICES). The study reported here concerns ways that affected individuals and organizations will respond to proposed ICES development projects. The intent is an initial examination of several institutional sectors that will: (1) anticipate responses that could impede ICES proposals and (2) provide an information base from which strategies to address adverse responses can be formulated.

  15. Factors Influencing Users Satisfaction on E-Learning Systems

    Directory of Open Access Journals (Sweden)

    Josua Tarigan

    2011-01-01

    Full Text Available User satisfaction has held a central role in an organization as one of the measurements for the success of service delivery. The objectives of this study are to evaluate user satisfaction and examine the association between user satisfaction and the qualities in the e-learning systems of Multionational Company. A theoretical framework is developed, through the integration of e-learning satisfaction (ELS theory and global satisfaction theory. The analysis was organized from a set of data which involve 190 responses from end-users. The main finding confirms some degree of a positive association between user satisfaction and the qualities in the e-learning system.

  16. Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases

    DEFF Research Database (Denmark)

    Tsushima, Y; Kanal, E; Thomsen, H S

    2010-01-01

    The aim of this article is to review the published cases of nephrogenic systemic fibrosis (NSF) in Japan. The Japanese medical literature database and MedLine were searched using the keywords NSF and nephrogenic fibrosing dermopathy (January 2000 to March 2009). Reports in peer-reviewed journals ...

  17. 75 FR 35096 - Federal Employees' Retirement System; Present Value Factors

    Science.gov (United States)

    2010-06-21

    ... by the Board of Actuaries of the Civil Service Retirement System. DATES: The revised present value.... ADDRESSES: Send requests for actuarial assumptions and data to the Board of Actuaries, care of Gregory Kissel, Actuary, Office of Planning and Policy Analysis, Office of Personnel Management, Room 4307, 1900...

  18. 76 FR 32243 - Federal Employees' Retirement System; Present Value Factors

    Science.gov (United States)

    2011-06-03

    ... adopted by the Board of Actuaries of the Civil Service Retirement System. DATES: The revised present value.... ADDRESSES: Send requests for actuarial assumptions and data to the Board of Actuaries, care of Gregory Kissel, Actuary, Office of Planning and Policy Analysis, Office of Personnel Management, Room 4307, 1900...

  19. 76 FR 32241 - Civil Service Retirement System; Present Value Factors

    Science.gov (United States)

    2011-06-03

    ... in the economic assumptions adopted by the Board of Actuaries of the Civil Service Retirement System... data to the Board of Actuaries, care of Gregory Kissel, Actuary, Office of Planning and Policy Analysis...- 335, based on changed economic assumptions adopted by the Board of Actuaries of the CSRS. Those...

  20. Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

    Science.gov (United States)

    Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

    2010-01-01

    Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour. PMID:19653930

  1. Structure design of human factor data management system for Daya Bay NPP

    International Nuclear Information System (INIS)

    Zhang Li; Zhang Ning; Guo Jianbing; Huang Weigang; Zhu Minhong; Wang Jin

    2000-01-01

    Collection, analysis and quantification of human factor data are important compositions of human reliability analysis (HRA) and probabilistic risk assessment (PRA). Various human factor databases have been set up, but there are comparatively little human factor data management systems which can be uses for collection, classification, analysis, calculation and predication of the human factor data. Therefore, the human factor data management system for Daya Bay NPP is developed, with the following three modules and four databases: original data module, computing module, introduced data module, and basic database, other data source of the plant, external database and introduced database. The foundational problems about human factor data and the systemic structure and function are described. The data structure in the database is also discussed, because it is of the most importance in the system

  2. Availability improvement factors at Taipower's nuclear power plant system

    International Nuclear Information System (INIS)

    Chen, J.H.

    1985-01-01

    Sufficient electricity to meet the needs of a growing industrial economy, is one of the most important factors in the total economic development of a nation. Currently, nuclear power is considered one of the most economical and available sources of energy. To keep pace with Taiwan's rapid economic development, while also observing our government's policy of diversifying the requirements for imported forms of energy, Taiwan Power Company has embarked upon an ambitious of nuclear power plant construction. This paper discusses the improvement of Taiwan's nuclear power plants. At the present time, Taipower has completed three nuclear power plants. Two of these are located in northern Taiwan, along the East China Sea, while the third is on the southern tip of Taiwan, bordering the South China Sea. These three plants, each with two nuclear generating units, comprise a total nuclear generating capacity of 5144 MWe

  3. Provider and systems factors in diabetes quality of care.

    Science.gov (United States)

    Ghaznavi, Kimia; Malik, Shaista

    2012-02-01

    A gap exists in knowledge and the observed frequency with which patients with diabetes actually receive treatment for optimal cardiovascular risk reduction. Many interventions to improve quality of care have been targeted at the health systems level and provider organizations. Changes in several domains of care and investment in quality by organizational leaders are needed to make long-lasting improvements. In the studies reviewed, the most effective strategies often have multiple components, whereas the use of one single strategy, such as reminders only or an educational intervention, is less effective. More studies are needed to examine the effect of several care management strategies simultaneously, such as use of clinical information systems, provider financial incentives, and organizational model on processes of care and outcomes.

  4. What Factors Affect the Prices of Low-Priced U.S. Solar PV Systems?

    Energy Technology Data Exchange (ETDEWEB)

    Nemet, Gregory F. [Univ. of Wisconsin, Madison, WI (United States); Mercator Research Inst. on Global Commons and Climate Change, Berlin (Germany); O' Shaughnessy, Eric [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wiser, Ryan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Darghouth, Naïm R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gillingham, Ken [Yale Univ., New Haven, CT (United States); Rai, Varun [Univ. of Texas, Austin, TX (United States)

    2016-08-01

    The price of solar PV systems has declined rapidly, yet there are some much lower-priced systems than others. This study explores the factors leading some systems to be so much lower priced than others. Using a data set of 42,611 residential-scale PV systems installed in the U.S. in 2013, we use quantile regressions to estimate the importance of factors affecting the installed prices for low-priced (LP) systems (those at the 10th percentile) in comparison to median-priced systems. We find that the value of solar to consumers–a variable that accounts for subsidies, electric rates, and PV generation levels–is associated with lower prices for LP systems but higher prices for median priced systems. Conversely, systems installed in new home construction are associated with lower prices at the median but higher prices for LP. Other variables have larger cost-reducing effects on LP than on median priced systems: systems installed in Arizona and Florida, as well as commercial and thin film systems. In contrast, the following have a smaller effect on prices for LP systems than median priced systems: tracking systems, self-installations, systems installed in Massachusetts, the system size, and installer experience. These results highlight the complex factors at play that lead to LP systems and shed light into how such LP systems can come about.

  5. Human Factors in Software Development Processes: Measuring System Quality

    DEFF Research Database (Denmark)

    Abrahão, Silvia; Baldassarre, Maria Teresa; Caivano, Danilo

    2016-01-01

    Software Engineering and Human-Computer Interaction look at the development process from different perspectives. They apparently use very different approaches, are inspired by different principles and address different needs. But, they definitively have the same goal: develop high quality software...... in the most effective way. The second edition of the workshop puts particular attention on efforts of the two communities in enhancing system quality. The research question discussed is: who, what, where, when, why, and how should we evaluate?...

  6. Design flow factors for sewerage systems in small arid communities

    OpenAIRE

    Imam, Emad H.; Elnakar, Haitham Y.

    2014-01-01

    Reliable estimation of sewage flow rates is essential for the proper design of sewers, pumping stations, and treatment plants. The design of the various components of the sewerage system should be based on the most critical flow rates with a focus on extremely low and peak flow rates that would be sustained for a duration related to the acceptable limits of behavior of the components under consideration. The extreme flow conditions and to what extent they differ from the average values are cl...

  7. An Empirical Investigation of Factors Influencing Knowledge Management System Success

    Science.gov (United States)

    2008-03-01

    International Conference on System Sciences, Big Island, Hawaii. Coakes, S. J., & Steed, L. G. (1997), SPSS : Analysis without anguish . New York, NY...Statistical Package for the Social Sciences ( SPSS ) version 15 for Windows. Descriptive statistics were used to describe the samples. Multiple...Pearson’s correlation coefficient. Responses from the questionnaires were gathered and entered into SPSS 15 for Windows. The purpose of the Pearson’s

  8. Corrosion and Biofouling of OTEC System Surfaces - Design Factors

    Science.gov (United States)

    1978-11-01

    condition between different areas on a given member can lead to accelerated attack by a differential envirornment cell . These differences can be...resistance. As shown in Figure 1, -. gal- vanic cell is essentially a battery/load system. When the intermetallic resistance, R1 , or the environmental...members of a couple should be maximized when possible. Also, insulating or high resistance F bushings, etc., can reduce or el4 !.minate galvanic corrosion

  9. [Environmental pollutants as adjuvant factors of immune system derived diseases].

    Science.gov (United States)

    Lehmann, Irina

    2017-06-01

    The main task of the immune system is to protect the body against invading pathogens. To be able to do so, immune cells must be able to recognize and combat exogenous challenges and at the same time tolerate body-borne structures. A complex regulatory network controls the sensitive balance between defense and tolerance. Perturbation of this network ultimately leads to the development of chronic inflammation, such as allergies, autoimmune reactions, and infections, because the immune system is no longer able to efficiently eliminate invading pathogens. Environmental pollutants can cause such perturbations by affecting the function of immune cells in such a way that they would react hypersensitively against allergens and the body's own structures, respectively, or that they would be no longer able to adequately combat pathogens. This indirect effect is also known as adjuvant effect. For pesticides, heavy metals, wood preservatives, or volatile organic compounds such adjuvant effects are well known. Examples of the mechanism by which environmental toxins contribute to chronic inflammatory diseases are manifold and will be discussed along asthma and allergies.While the immune system of healthy adults is typically well able to distinguish between foreign and endogenous substances even under adverse environmental conditions, that of children would react much more sensible upon comparable environmental challenges. To prevent priming for diseases by environmental cues during that highly sensitive period of early childhood children are to be particularly protected.

  10. Evaluation of atopy through an expert system: description of the database.

    Science.gov (United States)

    Ray, P; Vervloet, D; Charpin, D; Gautier, V; Proudhon, H; Redier, H; Godard, P

    1995-11-01

    In order to understand the medical decisions taken during the initial visit of a new asthmatic patient, a group of experts designed an expert system which provides conclusions about severity, precipitating factors and treatment. Rules for atopy and the assessment of allergic factors have been discussed and implemented in the expert system. Conclusions about severity have been yet validated using an appropriate methodology. The aim of this study was to investigate a sample of 471 patients according to conclusions regarding atopy. A total of 471 cases report forms (CRF) was filled in for adult asthmatic outpatients, seen for the first time in our clinic without emergency situations. Data of each CRF were used by the expert system to draw conclusions. The expert system discerns three patterns for atopy, yes, possible or no. The variables known to reflect different features according to the classification of asthma as atopic or not have been studied. The variables used in the rules for atopy, obviously linked to the conclusion, were not compared. For many medical problems no unique objective solution exists and this is why a group of patients with possible atopy was introduced. Patients with atopy had less severe asthma (P = 0.01), a better FEV1 value (P = 0.0007) and showed their first symptoms of asthma earlier (P = 0.00001) than patients without atopy. The characteristics of the group studied here are consistent with the literature. This could be considered as an indirect validation of the expert system. Moreover, patients with possible atopy show intermediate findings for these variables and it is possible to suggest a 'dose-effect' relationship.

  11. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC) SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    OpenAIRE

    Karim MAMDOUH ABBAS

    2014-01-01

    The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC) system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms) in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC) in Eg...

  12. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  13. Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases

    DEFF Research Database (Denmark)

    Tsushima, Y; Kanal, E; Thomsen, H S

    2010-01-01

    The aim of this article is to review the published cases of nephrogenic systemic fibrosis (NSF) in Japan. The Japanese medical literature database and MedLine were searched using the keywords NSF and nephrogenic fibrosing dermopathy (January 2000 to March 2009). Reports in peer-reviewed journals...... and meeting abstracts were included, and cases with biopsy confirmation were selected. 14 biopsy-verified NSF cases were found. In seven of eight patients reported after the association between gadolinium-based contrast agent (GBCA) and NSF was proposed, GBCA administration was documented: five received only...

  14. Human factors issues in digital system design and implementation

    International Nuclear Information System (INIS)

    Galletti, Greg S.

    1998-01-01

    A goal of the U.S. Nuclear Regulatory Commission (NRC) is to ensure safety in the application of digital equipment upgrades to nuclear power plant control rooms and local control stations. One of the areas of specific interest is the integration of digital technology into existing analog control, display, and information systems and the implications of such integration for operators in regard to their use of this new equipment to safely operate the plant. This paper is a discussion of human performance issues related to the introduction of such digital equipment into operating nuclear power plants. (author)

  15. Cultural Factors in Systems Design Decision Making and Action

    CERN Document Server

    Proctor, Robert W; Yih, Yuehwern

    2011-01-01

    This book brings together an interdisciplinary group of experts to provide increased understanding of the ways in which cultural differences may influence decision making and action. It brings together current knowledge about decision processes, culture and cognition, design of products and interfaces for human interaction with machines and organizational processes culled from a wide variety of sources and puts them into one comprehensive resource. It examines how to design systems used by individuals from different cultures and accommodate the varied backgrounds that affect the users' decisio

  16. System-wide impacts of environmental cost factors

    International Nuclear Information System (INIS)

    Rogers, M.; Kennedy, T.; Finnell, J.; Hoelscher, J.

    1992-01-01

    This paper presents a continuum of approaches to considering environmental externalities in the utility resource selection process. While photovoltaic (PV) technologies can play a role in reducing emissions, they are generally not cost-competitive with conventional technologies, even when cost estimates for environmental damages are introduced. Several approaches are explored to determine whether PV becomes more competitive when emission reduction strategies are considered on a regional basis. Finally, preliminary analysis was performed with the Midas utility planning model to develop emission credits based on PV's ability to displace emissions on a net system basis

  17. FACTORS THAT POTENTIALLY AFFECT THE FINANCIAL SUSTAINABILITY OF THE PENSION SYSTEM IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Luise Mladen

    2017-06-01

    Full Text Available In Romania, the State Social Security Budget spending exceeds the revenues, and this situation leads to a growing deficit of the public budget. This evolution is the result of a complex of factors, more or less difficult to be managed, which we analyze in this article. The phenomenon of ageing has a significant role in increasing the pressure on the social protection systems, in general, and on the pension system, in particular. Also, the labour market related factors and the economic factors have an important impact on the sustainability of the pension system. The design of the pension system is equally important.

  18. GHRELIN ACTIVATES HYPOPHYSIOTROPIC CORTICOTROPIN-RELEASING FACTOR NEURONS INDEPENDENTLY OF THE ARCUATE NUCLEUS

    Science.gov (United States)

    Cabral, Agustina; Portiansky, Enrique; Sánchez-Jaramillo, Edith; Zigman, Jeffrey M.; Perello, Mario

    2016-01-01

    Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin’s orexigenic action vs. its role as a stress signal are anatomically dissociated. PMID:26874559

  19. Factors affecting sex education in the school system.

    Science.gov (United States)

    Woo, G W; Soon, R; Thomas, J M; Kaneshiro, B

    2011-06-01

    To describe the current status of school based sex education and to determine predictors of providing a comprehensive sex education curriculum. Cross-sectional mailed survey Hawaii Seventh and eighth grade health teachers Participants were surveyed regarding the content, quality, and influences on sex education for the 2007 to 2008 academic year. Measures of association (chi-square, ANOVA) and multiple logistic regression were used to determine predictors for teaching comprehensive sex education topics including sexually transmitted infections and pregnancy prevention. Approximately 80% of teachers incorporated some form of sex education into their curriculum and 54.4% of teachers incorporated a comprehensive education. Teachers indicated that personal values and the availability of curriculum had the greatest influence on the content of the curriculum. Specific factors which were associated with an increased likelihood of providing a comprehensive curriculum included teaching in a public school (public 66.7% versus private 34.6%, P = 0.01), receiving formal training in sex education (received training 77.8% versus did not receive training 50.0%, P = 0.03) and having contact with a student who became pregnant (contact 72.7% versus no contact 46.7%, P = 0.04). Although most teachers incorporate some form of sex education, only half incorporate a comprehensive curriculum. Personal values as well as teacher resources play an important role in the content of the curriculum. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  20. Sociotechnical factors influencing unsafe use of hospital information systems: A qualitative study in Malaysian government hospitals.

    Science.gov (United States)

    Salahuddin, Lizawati; Ismail, Zuraini; Hashim, Ummi Rabaah; Raja Ikram, Raja Rina; Ismail, Nor Haslinda; Naim Mohayat, Mohd Hariz

    2018-03-01

    The objective of this study is to identify factors influencing unsafe use of hospital information systems in Malaysian government hospitals. Semi-structured interviews with 31 medical doctors in three Malaysian government hospitals implementing total hospital information systems were conducted between March and May 2015. A thematic qualitative analysis was performed on the resultant data to deduce the relevant themes. A total of five themes emerged as the factors influencing unsafe use of a hospital information system: (1) knowledge, (2) system quality, (3) task stressor, (4) organization resources, and (5) teamwork. These qualitative findings highlight that factors influencing unsafe use of a hospital information system originate from multidimensional sociotechnical aspects. Unsafe use of a hospital information system could possibly lead to the incidence of errors and thus raises safety risks to the patients. Hence, multiple interventions (e.g. technology systems and teamwork) are required in shaping high-quality hospital information system use.

  1. Fast reactor system factors affecting reprocessing plant design

    International Nuclear Information System (INIS)

    Allardice, R.H.; Pugh, O.

    1982-01-01

    The introduction of a commercial fast reactor electricity generating system is very dependent on the availability of an efficient nuclear fuel cycle. Selection of fuel element constructional materials, the fuel element design approach and the reactor operation have a significant influence on the technical feasibility and efficiency of the reprocessing and waste management plants. Therefore the fast reactor processing plant requires liaison between many design teams -reactor, fuel design, reprocessing and waste management -often with different disciplines and conflicting objectives if taken in isolation and an optimised approach to determining several key parameters. A number of these parameters are identified and the design approach discussed in the context of the reprocessing plant. Radiological safety and its impact on design is also briefly discussed. (author)

  2. Analysis of the Important Factors for the LSDTS System

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Deok; Song, Jae Hoon; Park, Chang Je; Song, Kee Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-11-15

    It is confirmed that it is necessary to have domestic experience for measuring fissile material such as U-235, U-238, and Pu-239 in spent fuel or pyro-processed fuel containing TRU and to have technology related with measurement for fissile material. Understanding newly advanced measurement system for fissile material, it indicates the development directions. In this research, it is shown to the basic principle of LSDTS and it is investigated to commercial neutron source generator in order to use appropriated neutron source in the LSDTS. On the other hand, it is understood to the properties for fission chamber as induced neutron detector. It is confirmed to the relationship between slowing-down time and neutron energy in slowing-down medium. Understanding the application of SDTS, the efficiency is broaden, that is, it can help as equipment for real-time, direct, and quantitative measurement of fissile material from fuel assay such as spent fuel or pyro-processed fuel.

  3. Analysis of Factors Affect to Organizational Performance In Using Accounting Information Systems Through Users Satisfaction and Integration Information Systems

    Directory of Open Access Journals (Sweden)

    Anton Arisman

    2017-09-01

    Full Text Available The aim of this research is to investigate the factors affecting organizational performance in using accounting information system through users satisfaction and integration information systems. The research respondents were 447 companies that listed in Indonesian Stock Exchange. The data are gathered through consensus method and in total there are 176 responses with complete data. Structural Equation Model (SEM is used in analyzing the data and system theory is utilized in this research. The result shows that knowledge management systems and management control system have significant influence on users satisfaction and integration information systems.  Integration information system and users satisfaction has positive significant on organizational performance.

  4. On Signed Incomplete Cholesky Factorization Preconditioners for Saddle-Point Systems

    Czech Academy of Sciences Publication Activity Database

    Scott, J.; Tůma, Miroslav

    2014-01-01

    Roč. 36, č. 6 (2014), A2984-A3010 ISSN 1064-8275 R&D Projects: GA ČR GA13-06684S Grant - others:EPSRC(GB) EP/I013067/1 Program:GA Institutional support: RVO:67985807 Keywords : sparse matrices * sparse linear systems * indefinite symmetric systems * saddle-point systems * iterative solvers * preconditioning * incomplete Cholesky factorization Subject RIV: BA - General Mathematics Impact factor: 1.854, year: 2014

  5. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  6. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed

  7. The antioxidative system of Norway spruce: Effects of different stress factors. Das antioxidative System der Fichte: Einfluss von verschiedenen Stressfaktoren

    Energy Technology Data Exchange (ETDEWEB)

    Schittenhelm, J. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Westphal, S. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Toder, S. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Wagner, E. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany))

    1993-08-01

    The effects of different stress factors on the antioxidative system of 6-year-old Norway spruces of the same clone were examined. Flooding and permanent darkness had only minor effects. On the other hand drought, chilling, intense light, and very high ozone concentrations showed strong but distinct consequences. This indicates that the damages by these stress factors are due to different toxic oxygen species, and that the stress factors could produce synergistic damages under natural field conditions. (orig.)

  8. Looking under the Bonnet: Factors Affecting Student Adoption of E-Learning Systems in Jordan

    Directory of Open Access Journals (Sweden)

    Muneer Mahmood Abbad, David Morris, Carmel de Nahlik

    2009-04-01

    Full Text Available The primary questions addressed in this paper are the following: what are the factors that affect students’ adoption of an e-learning system and what are the relationships among these factors?This paper investigates and identifies some of the major factors affecting students’ adoption of an e-learning system in a university in Jordan. E-learning adoption is approached from the information systems acceptance point of view. This suggests that a prior condition for learning effectively using e-learning systems is that students must actually use them. Thus, a greater knowledge of the factors that affect IT adoption and their interrelationships is a pre-cursor to a better understanding of student acceptance of e-learning systems. In turn, this will help and guide those who develop, implement, and deliver e-learning systems.In this study, an extended version of the Technology Acceptance Model (TAM was developed to investigate the underlying factors that influence students’ decisions to use an e-learning system. The TAM was populated using data gathered from a survey of 486 undergraduate students using the Moodle based e-learning system at the Arab Open University. The model was estimated using Structural Equation Modelling (SEM. A path model was developed to analyze the relationships between the factors to explain students’ adoption of the e-learning system. Whilst findings support existing literature about prior experience affecting perceptions, they also point to surprising group effects, which may merit future exploration.

  9. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

    Science.gov (United States)

    Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

    2015-07-01

    Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Tumor necrosis factor receptor associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system

    Science.gov (United States)

    Walsh, Matthew C.; Lee, JangEun; Choi, Yongwon

    2016-01-01

    Summary Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of IL-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor (IRF) pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system, but also for maintaining immune tolerance, and more recent works have begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. PMID:26085208

  11. Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens.

    Science.gov (United States)

    Bunupuradah, Torsak; Ananworanich, Jintanat; Chetchotisakd, Ploenchan; Kantipong, Pacharee; Jirajariyavej, Supunnee; Sirivichayakul, Sunee; Munsakul, Warangkana; Prasithsirikul, Wisit; Sungkanuparph, Somnuek; Bowonwattanuwong, Chureeratana; Klinbuayaem, Virat; Petoumenos, Kathy; Hirschel, Bernard; Bhakeecheep, Sorakij; Ruxrungtham, Kiat

    2011-01-01

    We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA>1,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS; ≥ 4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS; 2.5-3.5 and ≥ 4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Median (IQR) age was 38 (34-42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8-4.5) years. Median (IQR) CD4(+) T-cell count and HIV RNA were 194 (121-280) cells/mm³ and 4.1 (3.6-4.6) log₁₀ copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥ 4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5-3.5 and ≥4, respectively. Only HIV RNA ≥ 4 log₁₀ copies/ml at failure was associated with both Monogram WS ≥ 4 (OR 2.3, 95% CI 1.3-3.9; P=0.003) and DUET WS ≥ 2.5 (OR 1.9, 95% CI 1.1-3.3; P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.

  12. The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

    Science.gov (United States)

    Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2012-08-03

    N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

  13. Biomaterial-based drug delivery systems for the controlled release of neurotrophic factors

    International Nuclear Information System (INIS)

    Mohtaram, Nima Khadem; Montgomery, Amy; Willerth, Stephanie M

    2013-01-01

    This review highlights recent work on the use of biomaterial-based drug delivery systems to control the release of neurotrophic factors as a potential strategy for the treatment of neurological disorders. Examples of neurotrophic factors include the nerve growth factor, the glial cell line-derived neurotrophic factor, the brain-derived neurotrophic factor and neurotrophin-3. In particular, this review focuses on two methods of drug delivery: affinity-based and reservoir-based systems. We review the advantages and challenges associated with both types of drug delivery system and how these systems can be applied to neurological diseases and disorders. While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels and combinations of these systems. Finally, conclusions are drawn about the current state of such drug delivery systems as applied to neural tissue engineering along with some thoughts on the future direction of the field. (topical review)

  14. A study to determine influential factors on implementation of management information system

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2013-08-01

    Full Text Available Management information system (MIS plays an important role on sharing necessary information within organization. In this paper, we study to find out important factors influencing the implementation of MIS in banking industry. The study designs a questionnaire in Likert scale and distributes it among 253 randomly selected people. Cronbach alpha has been calculated as 0.82, which is within an acceptable limit. The study uses factor analysis to find important factors and detects six important factors including fear of technology, organizational instability, informal groups, cultural factors, organizational development and understanding that change is always good.

  15. An exploration study to find important factors influencing on expert systems

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2013-09-01

    Full Text Available Knowledge management plays an important role in modern management systems since many existing systems move towards learning organizations. Expert systems, on the other hand, are considered as the most popular techniques for adapting recent developments on knowledge management. This paper presents an empirical investigation to find important factors influencing adaptation of expert systems. The proposed study designs a questionnaire in Likert scale consists of 25 questions, distributes it among 258 people who have recently graduated from computer science and they are familiar with implementation of expert systems. Cronbach alpha is calculated as 0.730 and Kaiser-Meyer-Olkin Measure of Sampling Adequacy and Approx. Chi-Square are 0.748 and 1377.397, respectively. The study has implemented principal component analysis and the results have indicated that there were four factors influencing expert systems including systems management, intelligence systems, system analysis and specialized analysis.

  16. Optimization of a multi-gene HIV-1 recombinant subtype CRF02AG DNA vaccine for expression of multiple immunogenic forms

    International Nuclear Information System (INIS)

    Ellenberger, Dennis; Li Bin; Smith, James; Yi Hong; Folks, Thomas; Robinson, Harriet; Butera, Salvatore

    2004-01-01

    We developed an AIDS vaccine for Western and West-Central Africa based on a DNA plasmid vector expressing HIV-1 recombinant subtype CRF02 A G gag, pol, and env genes. To optimize the production of noninfectious HIV-like particles (VLPs) and potentially improve the effectiveness of the vaccine, we generated four potential vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and IC90) containing mutations within the HIV protease. While the parental construct IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the production of immature VLPs (the core comprises unprocessed Pr 55Gag ). The remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises processed capsid p24) in addition to immature VLPs and aggregates of Gag proteins. VLPs incorporated significant levels of mature gp120 envelope glycoprotein. Importantly, the mature VLPs were fusion competent and entered coreceptor-specific target cells. The production of multiple antigenic forms, including fusion-competent VLPs, by candidate DNA vaccine constructs may provide immunologic advantages for induction of protective cellular and humoral responses against HIV-1 proteins

  17. Rare HIV-1 Subtype J Genomes and a New H/U/CRF02_AG Recombinant Genome Suggests an Ancient Origin of HIV-1 in Angola.

    Science.gov (United States)

    Bártolo, Inês; Calado, Rita; Borrego, Pedro; Leitner, Thomas; Taveira, Nuno

    2016-08-01

    Angola has an extremely diverse HIV-1 epidemic fueled in part by the frequent interchange of people with the Democratic Republic of Congo (DRC) and Republic of Congo (RC). Characterization of HIV-1 strains circulating in Angola should help to better understand the origin of HIV-1 subtypes and recombinant forms and their transmission dynamics. In this study we characterize the first near full-length HIV-1 genomic sequences from HIV-1 infected individuals from Angola. Samples were obtained in 1993 from three HIV-1 infected patients living in Cabinda, Angola. Near full-length genomic sequences were obtained from virus isolates. Maximum likelihood phylogenetic tree inference and analyses of potential recombination patterns were performed to evaluate the sequence classifications and origins. Phylogenetic and recombination analyses revealed that one virus was a pure subtype J, another mostly subtype J with a small uncertain region, and the final virus was classified as a H/U/CRF02_AG recombinant. Consistent with their epidemiological data, the subtype J sequences were more closely related to each other than to other J sequences previously published. Based on the env gene, taxa from Angola occur throughout the global subtype J phylogeny. HIV-1 subtypes J and H are present in Angola at low levels since at least 1993. Low transmission efficiency and/or high recombination potential may explain their limited epidemic success in Angola and worldwide. The high diversity of rare subtypes in Angola suggests that Angola was part of the early establishment of the HIV-1 pandemic.

  18. The human factor data management system of Daya Bay Nuclear Power Station

    International Nuclear Information System (INIS)

    Zhang Li; Zhang Ning; Guo Jianbing; Huang Weigang; Zhu Minhong; Wang Jin

    1999-12-01

    The collection, analysis and quantification of human factor data are very important parts of human reliability analysis and probabilistic risk assessment. Therefore various human databases have been created. But a human data management system with the functions of data collection, classification, analysis, computation and forecast is scarcely seen at home and abroad. So the authors have developed the human data management system of Daya Bay Nuclear Power Station. The system includes three modules and four databases. The authors firstly set forth some basic problems on the human factor data, which are concerned during the development of the system. Then the structure and function of the system are described. In view of the important role of human factor databases in the system, the authors also discuss the structure problems of the data in the databases in detail

  19. Human factors programs for high-level radioactive waste handling systems

    International Nuclear Information System (INIS)

    Pond, D.J.

    1992-01-01

    Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples form other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

  20. Human factors programs for high-level radioactive waste handling systems

    International Nuclear Information System (INIS)

    Pond, D.J.

    1992-04-01

    Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples from other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

  1. Integrated application of human factors to a power plant control room information system

    International Nuclear Information System (INIS)

    Fish, H.C. Jr.; Gutierrez, R.

    1988-01-01

    The human factors plan was developed as a methodology to apply human factors from the conceptual design of the EPIC system to the functional verification conducted at the plant. An integral part of the Human Factors Plan was the Functional Verification Plan. Developed in parallel, this second plan and its resultant programs verified functional appropriateness of the SPDS display, NSSS displays, EOP displays, man-machine interfaces (MMI), and workstation designs. The functional verification process was performed at the hardware/software developer's factory and at the JAFNPP, following installation of the EPIC system. Because the EPIC system replaces existing control room equipment, it is important that human factors be applied in a systematic manner consistent with other control room displays and controls. To ensure that this goal was met, a human factors plan was developed

  2. Calculation and application of energy transaction allocation factors in electric power transmission systems

    Science.gov (United States)

    Fradi, Aniss

    The ability to allocate the active power (MW) loading on transmission lines and transformers, is the basis of the "flow based" transmission allocation system developed by the North American Electric Reliability Council. In such a system, the active power flows must be allocated to each line or transformer in proportion to the active power being transmitted by each transaction imposed on the system. Currently, this is accomplished through the use of the linear Power Transfer Distribution Factors (PTDFs). Unfortunately, no linear allocation models exist for other energy transmission quantities, such as MW and MVAR losses, MVAR and MVA flows, etc. Early allocation schemes were developed to allocate MW losses due to transactions to branches in a transmission system, however they exhibited diminished accuracy, since most of them are based on linear power flow modeling of the transmission system. This thesis presents a new methodology to calculate Energy Transaction Allocation factors (ETA factors, or eta factors), using the well-known process of integration of a first derivative function, as well as consistent and well-established mathematical and AC power flow models. The factors give a highly accurate allocation of any non-linear system quantity to transactions placed on the transmission system. The thesis also extends the new ETA factors calculation procedure to restructure a new economic dispatch scheme where multiple sets of generators are economically dispatched to meet their corresponding load and their share of the losses.

  3. Lithium isotope separation factors of some two-phase equilibrium systems

    International Nuclear Information System (INIS)

    Palko, A.A.; Drury, J.S.; Begun, G.M.

    1976-01-01

    Isotope separation factors of seventeen two-phase equilibrium systems for lithium isotope enrichment have been determined. In all cases, lithium amalgam was used as one of the lithium-containing phases and was equilibrated with an aqueous or organic phase containing a lithium compound. In all systems examined, isotopic exchange was found to be extremely rapid, and 6 Li was concentrated in the amalgam phase. The isotopic separation factor for the LiOH(aqueous) vs Li(amalgam) system has been studied as a function of temperature from -2 to 80 degreeC. The values obtained have been compared with the ''electrolysis'' and exchange separation factors given in the literature. The two-phase systems, LiCl(ethylenediamine) vs Li(amalgam) and LiCl(propylenediamine) vs Li(amalgam), have been studied, and the isotopic separation factors have been determined as functions of the temperature. The factors for the two systems have been found to be substantially the same (within limits of the errors involved) over the temperature range studied (0 to 100 degreeC) as those for the aqueous system. The isotopic separation factors for the seventeen systems have been tabulated, and correlations have been drawn that show the salt and solvent effects upon the values obtained

  4. RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

    Directory of Open Access Journals (Sweden)

    Zh.P. Sharnova

    2006-01-01

    Full Text Available To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

  5. Determination of OB/OD/SF Emission Factors Using Unmanned Aerial Systems

    Science.gov (United States)

    A presentation to the Demilitarization Symposium. This proposal will present the methods of tethered aerostat and unmanned aerial system for collection of plume samples and determination of emission factors form open burning, open detonation, and static firing for weapon demilita...

  6. Factors Affecting Innovation Within Aeronautical Systems Center (ASC) Organizations - An inductive Study

    National Research Council Canada - National Science Library

    Feil, Eric

    2003-01-01

    .... This thesis analyzed data collected during the 2002 Chief of Staff of the Air Force Organizational Climate Survey to identify factors that affect innovation within Aeronautical Systems Center (ASC) organizations...

  7. Design factors of sensors for the optical tracking systems of solar concentrators

    International Nuclear Information System (INIS)

    Klychev, Sh. I.; Fazylov, A. K.; Orlov, S. A.; Burbo, A. V.

    2011-01-01

    Basic diagrams for the sensors of the optical tracking systems of solar concentrators are considered, the design factors that determine their accuracy are analyzed, a new sensor design is suggested, and its optimal parameters are determined. (authors)

  8. Behavioral Risk Factor Surveillance System (BRFSS) Prevalence Data (2010 and prior)

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2010. BRFSS land line only prevalence data. BRFSS is a continuous, state-based surveillance system that collects information about modifiable risk factors for...

  9. Examination of Factors Impacting Student Satisfaction with a New Learning Management System

    Science.gov (United States)

    Green, Lucy Santos; Inan, Fethi A.; Denton, Bree

    2012-01-01

    The purpose of this study was to determine factors that influenced student satisfaction with a new learning management system and to identify which of these factors were most important. The data was collected using an an online survey tool that was administered to students enrolled in courses designed and taught by faculty who participated in a…

  10. 2010 Critical Success Factors for the North Carolina Community College System. Twenty First Annual Report

    Science.gov (United States)

    North Carolina Community College System (NJ1), 2010

    2010-01-01

    First mandated by the North Carolina General Assembly in 1989 (S.L. 1989; C. 752; S. 80), the Critical Success Factors report has evolved into the major accountability document for the North Carolina Community College System. This twenty first annual report on the critical success factors is the result of a process undertaken to streamline and…

  11. General Open Systems Theory and the Substrata-Factor Theory of Reading.

    Science.gov (United States)

    Kling, Martin

    This study was designed to extend the generality of the Substrata-Factor Theory by two methods of investigation: (1) theoretically, to est"blish the validity of the hypothesis that an isomorphic relationship exists between the Substrata-Factor Theory and the General Open Systems Theory, and (2) experimentally, to disc"ver through a…

  12. The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary intervention Strategies

    NARCIS (Netherlands)

    Voskuil, D.W.; Vrieling, A.; Veer, van 't L.J.; Kampman, E.; Rookus, M.A.

    2005-01-01

    The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk

  13. The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies.

    NARCIS (Netherlands)

    Voskuil, D.W.; Vrieling, A.; Veer, L.J. van 't; Kampman, E.; Rookus, M.A.

    2005-01-01

    The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk

  14. Age and other perioperative risk factors for postoperative systemic inflammatory response syndrome after cardiac surgery

    NARCIS (Netherlands)

    Dieleman, J. M.; Peelen, L. M.; Coulson, T. G.; Tran, L.; Reid, C. M.; Smith, Jennifer A.; Myles, P. S.; Pilcher, C.D.

    2017-01-01

    Background The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic

  15. Radio immune analysis of endocrine system state at exposure to different physical factors

    International Nuclear Information System (INIS)

    Rozdyil's'ka, O.M.; Rozdtil's'kij, S.Yi.; Bratchuk, O.M.; Yakimova, T.P.

    1999-01-01

    Radio immune analysis allows to define more exactly the mechanisms of physical factors action and may be used for validation of new therapeutic techniques. The ultra-high frequency magneto therapy, sinusoid modulated current and direct current influence the state of the endocrine system differently but within the physiological norm. The most prominent action of the physical factor is observed at trans cerebral mode

  16. Factors Affecting the Full Use of Library and Information Management Systems by Library Personnel

    Science.gov (United States)

    Skretas, Georgios

    2005-01-01

    Purpose: To provide a general list of factors that affects and determines the full use of library information management systems (LIMS) by library staff. Design/methodology/approach: The factors, which were identified mainly during participation in the implementation of automation projects in Greece, are listed and briefly analysed in categories…

  17. Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas

    DEFF Research Database (Denmark)

    Vinter-Jensen, Lars; Juhl, C O; Teglbjaerg, P S

    1997-01-01

    Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and the EGF receptor are often overexpressed in chronic pancreatitis and in malignant pancreatic growth. Transgenic mice overexpressing TGF-alpha develop tissue changes in the pancrease resembling changes found in chronic...... pancreatitis. The effects of systemic treatment with EGF on the porcine pancrease were investigated in this study....

  18. Determination of the Level of Influence of Various Factors on the Reliability of Power System

    Directory of Open Access Journals (Sweden)

    Victor Popescu

    2014-09-01

    Full Text Available Consumers supply with qualitative electric power is one of the priority requirements imposed to power systems. Currently, in electricity networks take place a number of planned and unplanned disconnections, which interrupt the power and affect consumers, causing economic damage. To ensure the quality of power supply it is essential to know the factors that influence the reliability of power systems, which have a visible impact on the variation of reliability of equipment installed in power systems. This paper is devoted to problems of calculation and analysis of power systems reliability and estimation of the impact of various factors that influence the supply of consumers.

  19. Sensitivity evaluation of human factors for reliability of the containment spray system

    International Nuclear Information System (INIS)

    Tsujimura, Yasuhiro; Suzuki, Eiji

    1988-01-01

    Evaluation of the human reliability is one of the most difficult problems that deal with the safety and reliability of large systems, especially of the Engineered Safety Features (ESF) of the nuclear power plant. Influences of human factors on the reliability of the Containment Spray System in the ESF were estimated by using the FTA method in this paper. As a result, the adequacy of the system structure and the effects of human factors on variations of the design of the system structure were explained. (author)

  20. Common and divergent structural features of a series of corticotropin releasing factor-related peptides.

    Science.gov (United States)

    Grace, Christy Rani R; Perrin, Marilyn H; Cantle, Jeffrey P; Vale, Wylie W; Rivier, Jean E; Riek, Roland

    2007-12-26

    Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

  1. Modeling Indicator Systems for Evaluating Environmental Sustainable Development Based on Factor Analysis

    Institute of Scientific and Technical Information of China (English)

    WU Hao; CHEN Xiaoling; HE Ying; HE Xiaorong; CAI Xiaobin; XU Keyan

    2006-01-01

    Indicator systems of environmental sustainable development in the Poyang Lake Basin are established from 51 elementary indexes by factor analysis, which is composed of four steps such as the factor model, the parameter estimation, the factor rotation and the factor score. Under the condition that the cumulative proportion is greater than 85%, 5 explicit factors of environmental sustainable development as well as its factor score by region are carried out. The result indicates some impact factors to the basin environmental in descending sort order are volume of water, volume of waste gas discharge, volume of solid wastes, the degree to comprehensive utilization of waste gas, waste water and solid wastes, the emission volume of waste gas, waste water and solid wastes. It is helpful and important to provide decision support for constituting sustainable development strategies and evaluate the sustainable development status of each city.

  2. A Human Factors Approach to Bridging Systems and Introducing New Technologies

    Science.gov (United States)

    Kanki, Barbara G.

    2011-01-01

    The application of human factors in aviation has grown to cover a wide range of disciplines and methods capable of assessing human-systems integration at many levels. For example, at the individual level, pilot workload may be studied while at the team level, coordinated workload distribution may be the focal point. At the organizational level, the way in which individuals and teams are supported by training and standards, policies and procedures may introduce additional, relevant topics. A consideration of human factors at each level contributes to our understanding of successes and failures in pilot performance, but this system focused on the flight deck alone -- is only one part of the airspace system. In the FAA's NextGen plan to overhaul the National Airspace System (NAS), new capabilities will enhance flightdeck systems (pilots), flight operations centers (dispatchers) and air traffic control systems (controllers and air traffic managers). At a minimum, the current roles and responsibilities of these three systems are likely to change. Since increased automation will be central to many of the enhancements, the role of automation is also likely to change. Using NextGen examples, a human factors approach for bridging complex airspace systems will be the main focus of this presentation. It is still crucial to consider the human factors within each system, but the successful implementation of new technologies in the NAS requires an understanding of the collaborations that occur when these systems intersect. This human factors approach to studying collaborative systems begins with detailed task descriptions within each system to establish a baseline of the current operations. The collaborative content and context are delineated through the review of regulatory and advisory materials, letters of agreement, policies, procedures and documented practices. Field observations and interviews also help to fill out the picture. Key collaborative functions across systems

  3. Human factors analysis and design methods for nuclear waste retrieval systems. Volume II. A compendium of human factors design data

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-04-01

    This document is a compilation of human factors engineering design recommendations and data, selected and organized to assist in the design of a nuclear waste retrieval system. Design guidelines from a variety of sources have been evaluated, edited, and expanded for inclusion in this document, and, where appropriate, portions of text from selected sources have been included in their entirety. A number of human factors engineering guidelines for equipment designers have been written over the past three decades, each tailored to the needs of the specific system being designed. In the case of this particular document, a review of the preliminary human operator functions involved in each phase of the retrieval process was performed, resulting in the identification of areas of design emphasis upon which this document should be based. Documents containing information and design data on each of these areas were acquired, and data and design guidelines related to the previously identified areas of emphasis were extracted and reorganized. For each system function, actions were first assigned to operator and/or machine, and the operator functions were then described. Separate lists of operator functions were developed for each of the areas of retrieval activities - survey and mapping, remining, floor flange emplacement, plug and canister overcoring, plug and canister removal and transport, and CWSRS activity. These functions and the associated man-machine interface were grouped into categories based on task similarity, and the principal topics of human factors design emphasis were extracted. These topic areas are reflected in the contents of the 12 sections of this document

  4. The mathematical pathogenetic factors analysis of acute inflammatory diseases development of bronchopulmonary system among infants

    Directory of Open Access Journals (Sweden)

    G. O. Lezhenko

    2017-10-01

    Full Text Available The purpose. To study the factor structure and to establish the associative interaction of pathogenetic links of acute diseases development of the bronchopulmonary system in infants.Materials and methods. The examination group consisted of 59 infants (average age 13.8 ± 1.4 months sick with acute inflammatory bronchopulmonary diseases. Also we tested the level of 25-hydroxyvitamin D (25(ОНD, vitamin D-binding protein, hBPI, cathelicidin LL-37, ß1-defensins, lactoferrin in blood serum with the help of immunoenzymometric analysis. Selection of prognostically important pathogenetic factors of acute bronchopulmonary disease among infants was conducted using ROC-analysis. The procedure for classifying objects was carried out using Hierarchical Cluster Analysis by the method of Centroid-based clustering. Results. Based on the results of the ROC-analysis were selected 15 potential predictors of the development of acute inflammatory diseases of the bronchopulmonary system among infants. The factor analysis made it possible to determine the 6 main components . The biggest influence in the development of the disease was made by "the anemia factor", "the factor of inflammation", "the maternal factor", "the vitamin D supply factor", "the immune factor" and "the phosphorus-calcium exchange factor” with a factor load of more than 0.6. The performed procedure of hierarchical cluster analysis confirmed the initial role of immuno-inflammatory components. The conclusions. The highlighted factors allowed to define a group of parameters, that must be influenced to achieve a maximum effect in carrying out preventive and therapeutic measures. First of all, it is necessary to influence the "the anemia factor" and "the calcium exchange factor", as well as the "the vitamin D supply factor". In other words, to correct vitamin D deficiency and carry out measures aimed at preventing the development of anemia. The prevention and treatment of the pathological course of

  5. Analysis on nuclear power plant control room system design and improvement based on human factor engineering

    International Nuclear Information System (INIS)

    Gao Feng; Liu Yanzi; Sun Yongbin

    2014-01-01

    The design of nuclear power plant control room system is a process of improvement with the implementation of human factor engineering theory and guidance. The method of implementation human factor engineering principles into the nuclear power plant control room system design and improvement was discussed in this paper. It is recommended that comprehensive address should be done from control room system function, human machine interface, digital procedure, control room layout and environment design based on the human factor engineering theory and experience. The main issues which should be paid more attention during the control room system design and improvement also were addressed in this paper, and then advices and notices for the design and improvement of the nuclear power plant control room system were afforded. (authors)

  6. Radiometric calibration of wide-field camera system with an application in astronomy

    Science.gov (United States)

    Vítek, Stanislav; Nasyrova, Maria; Stehlíková, Veronika

    2017-09-01

    Camera response function (CRF) is widely used for the description of the relationship between scene radiance and image brightness. Most common application of CRF is High Dynamic Range (HDR) reconstruction of the radiance maps of imaged scenes from a set of frames with different exposures. The main goal of this work is to provide an overview of CRF estimation algorithms and compare their outputs with results obtained under laboratory conditions. These algorithms, typically designed for multimedia content, are unfortunately quite useless with astronomical image data, mostly due to their nature (blur, noise, and long exposures). Therefore, we propose an optimization of selected methods to use in an astronomical imaging application. Results are experimentally verified on the wide-field camera system using Digital Single Lens Reflex (DSLR) camera.

  7. Analysis of the Factors Affecting Resistance to Changes in Management Accounting Systems

    Directory of Open Access Journals (Sweden)

    Rodrigo Angonese

    2014-12-01

    Full Text Available Despite changes in the environment and management accounting practices, studies indicate that management accounting systems do not change or change at a much slower rate than expected. The stability of the management accounting systems used by companies may relate to resistance to changing these systems. This study analyzes the factors that contribute to resistance to implementing an integrated management system from the perspective of institutional theory, grounded in the old institutional economics. Methodologically, this study provides a qualitative assessment of the problem and a descriptive analysis of the resistance factors through a case-study approach. The data were collected using semi-structured interviews and analyzed through content analysis. Two companies were selected for this study due to their differing characteristics. The following seven factors were analyzed for resistance to implementing integrated management systems: institutional power, ontological insecurity, trust, inertia, lack of knowledge, acceptance of routines and decoupling. However, there was no evidence to characterize hierarchical power. The research findings indicate that changing management accounting systems, through the implementation of an integrated management system, faces internal resistance in these organizations. Each factor varies in intensity but is permanently present in these companies, such as ontological insecurity, trust, inertia, lack of knowledge, acceptance of routines and decoupling. These factors are awakened when the change process begins and, if they gather enough force, can stop the change.

  8. Power Factor Correction Capacitors for Multiple Parallel Three-Phase ASD Systems

    DEFF Research Database (Denmark)

    Yang, Yongheng; Blaabjerg, Frede

    2017-01-01

    Today’s three-phase Adjustable Speed Drive (ASD) systems still employ Diode Rectifiers (DRs) and Silicon-Controlled Rectifiers (SCRs) as the front-end converters due to structural and control simplicity, small volume, low cost, and high reliability. However, the uncontrollable DRs and phase......-controllable SCRs bring side-effects by injecting high harmonics to the grid, which will degrade the system performance in terms of lowering the overall efficiency and overheating the system if remain uncontrolled or unattenuated. For multiple ASD systems, certain harmonics in the entire system can be mitigated...... the power factor, passive capacitors can be installed, which yet can trigger the system resonance. Hence, this paper analyzes the resonant issues in multiple ASD systems with power factor correction capacitors. Potential damping solutions are summarized. Simulations are carried out, while laboratory tests...

  9. The human factor in operation and maintenance of complex high-reliability systems

    International Nuclear Information System (INIS)

    Ryan, T.G.

    1989-01-01

    Human factors issues in probabilistic risk assessment (PRAs) of complex high-reliability systems are addressed. These PRAs influence system operation and technical support programs such as maintainability, test, and surveillance. Using the U.S. commercial nuclear power industry as the setting, the paper addresses the manner in which PRAs currently treat human performance, the state of quantification methods and source data for analyzing human performance, and the role of human factors specialist in the analysis. The paper concludes with a presentation of TALENT, an emerging concept for fully integrating broad-based human factors expertise into the PRA process, is presented. 47 refs

  10. The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus.

    Science.gov (United States)

    Miele, Emily M; Headley, Samuel A E

    2017-09-12

    Aerobic exercise training is a component of diabetes mellitus (DM) care guidelines due to its favorable effects on glycemic control and cardiovascular disease (CVD) risk factors. The purpose of this review is to outline the recent evidence regarding the clinical effects of chronic aerobic exercise on CVD risk factors in persons with DM and to compare the effects of varying intensities and types of exercise. Among individuals with DM, all types of aerobic exercise training can impact positively on some traditional and non-traditional risk factors for CVD. Training programs with a higher volume or intensity induce greater improvements in vascular function, cardiorespiratory fitness (CRF), and lipid profiles. The beneficial outcomes of aerobic training include improvements in glycemic control, endothelial function, oxidative stress, dyslipidemia, myocardial function, adiposity, and CRF. Findings regarding markers of inflammation are discrepant and further research should focus on the role of exercise to impact upon the chronic inflammation associated with DM.

  11. Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals.

    Science.gov (United States)

    Moussaieff, Arieh; Gross, Moshe; Nesher, Elimelech; Tikhonov, Tatiana; Yadid, Gal; Pinhasov, Albert

    2012-12-01

    Incensole acetate (IA), a constituent of Boswellia resin ('frankincense'), was previously demonstrated to exhibit an antidepressive-like effect in the Forced Swim Test (FST) in mice following single dose administration (50 mg/kg). Here, we show that acute administration of considerably lower dose (10 mg/kg) IA to selectively bred mice, showing prominent submissive behavior, exerted significant antidepressant-like effects in the FST. Furthermore, chronic administration of 1 or 5 mg/kg per day of IA for three consecutive weeks dose- and time-dependently reduced the submissiveness of the mice in the Dominant-Submissive Relationship test, developed to screen the chronic effect of antidepressants. This behavioral effect was concomitant to reduced serum corticosterone levels, dose-dependent down-regulation of corticotropin releasing factor and up-regulation of brain derived neurotrophic factor transcripts IV and VI expression in the hippocampus. These data suggest that IA modulates the hypothalamic-pituitary-adrenal (HPA) axis and influences hippocampal gene expression, leading to beneficial behavioral effects supporting its potential as a novel treatment of depressive-like disorders.

  12. Service Quality: A Main Determinant Factor for Health Information System Success in Low-resource Settings.

    Science.gov (United States)

    Tilahun, Binyam; Fritz, Fleur

    2015-01-01

    With the increasing implementation of different health information systems in developing countries, there is a growing need to measure the main determinants of their success. The results of this evaluation study on the determinants of HIS success in five low resource setting hospitals show that service quality is the main determinant factor for information system success in those kind of settings.

  13. Acceptance and Success Factors for M-Learning of ERP Systems Curricula

    Science.gov (United States)

    Scholtz, Brenda; Kapeso, Mando

    2014-01-01

    The effective training of users is a key factor of the success of Enterprise Resource Planning (ERP) system projects. This need for ERP system training is exacerbated by a demand for quality ERP consultants which is evident in Europe and in African countries, particularly in South Africa where science and technology education has been identified…

  14. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

    Science.gov (United States)

    Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

    2012-09-01

    Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  15. Human Factors and Data Fusion as Part of Control Systems Resilience

    Energy Technology Data Exchange (ETDEWEB)

    David I. Gertman

    2009-05-01

    Human performance and human decision making is counted upon as a crucial aspect of overall system resilience. Advanced control systems have the potential to provide operators and asset owners a wide range of data, deployed at different levels that can be used to support operator situation awareness. However, the sheer amount of data available can make it challenging for operators to assimilate information and respond appropriately. This paper reviews some of the challenges and issues associated with providing operators with actionable state awareness and argues for the over arching importance of integrating human factors as part of intelligent control systems design and implementation. It is argued that system resilience is improved by implementing human factors in operations and maintenance. This paper also introduces issues associated with resilience and data fusion and highlights areas in which human factors including field studies hold promise.

  16. A review of privacy and usability issues in mobile health systems: Role of external factors.

    Science.gov (United States)

    Katusiime, Jane; Pinkwart, Niels

    2017-10-01

    The increased penetration of mobile devices has created opportunities in the health sector and led to emerging of mobile health systems. As much as the mobile health systems have registered tremendous progress, they have been faced with privacy and usability issues. Due to the sensitivity of health information, there is an ethical need to equip mobile health systems with adequate privacy measures. However, these systems should also be useable by the intended users. Even though many researchers are working on solutions, the issues still persist. External factors such as cultural differences have also contributed to the issues, yet they have been under researched. In this article, we conduct a systematic literature review of 22 articles, categorize and present privacy and usability issues and possible solutions. We then discuss the relevance and implications of external factors to the findings on privacy and usability. We end with recommendations to address these external factors.

  17. Stress factors for the deformation systems of zirconium under multiaxial stress

    International Nuclear Information System (INIS)

    Hobson, D.O.

    1976-01-01

    Calculation of the resolved shear stresses (rss) that act on various deformation systems in metals and, in particular, the determination of those systems subjected to the highest rss by a given set of multiaxial stresses is of importance in the study of texture development, yielding and plastic flow. This study examines the geometrical influences of any stress state on the deformation modes of zirconium. One slip mode and three twinning modes, comprising twenty-one deformation systems, are considered. Stress factors computed for these systems are shown on a coordinate system that allows specimen orientation, most highly stressed deformation system, and stress factor to be shown without ambiguity. The information in this report allows the determination of the rss that results from any multiaxial stress state; this information also allows the prediction of the deformation modes that might operate for any specimen orientation in that strss state

  18. Major factors in critical equipment reliability - Auxiliary systems; The development of an auxiliary system

    International Nuclear Information System (INIS)

    Forsthoffer, W.E.

    1992-01-01

    In this article, the author details the development of an actual auxiliary system in order to fully understand the function of each major component and how it contributes to the total operation and reliability of the system. Only after the function of an auxiliary system is thoroughly understood, can one proceed to discuss specifications, design audits, testing, operation and preventive maintenance. The application selected will be to develop a pressurized lubrication and steam turbine control oil system for the critical equipment unit. This example was selected since many readers will be familiar with this type and because it provides a good foundation towards understanding fluid sealing systems. In the exercise that follow, he will define the system requirements and determine the system parameters. This information will then be used for component sizing

  19. Associated factors and prevalence of erectile dysfunction in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Marcio Rodrigues Costa

    2014-01-01

    Full Text Available Purpose: The proposal of this study was to determine the prevalence and the associated factors of erectile dysfunction (ED among hemodialysis (HD patients. Materials and Methods: This was a cross-sectional study based on data collected from HD male patients. Clinical, demographic and laboratory data of all patients were collected in three HD clinics from December 2010 to June 2011. Patients answered questions of erectile function domain from International Index of Erectile Function. Data were evaluated by descriptive analysis and by univariate (ULRA and multivariate logistic regression analysis (MLRA. Results: Three hundred and five patients participated of the study. The prevalence of ED was 68.19%. ED was associated with diabetes (DM, benign prostatic hyperplasia, glomerulonephritis as cause of chronic renal failure (CRF, smoking habits, lower creatinine levels (ULRA, use of calcium channel blocker (MLRA, aging, lower education level, alcohol consumption, DM (as cause of CRF and coronary insufficiency (ULRA and MLRA. Conclusions: ED was highly prevalent in the HD men. It was independently associated with aging, current use of alcohol, long alcohol use (even for those who do not drink more, lower education level, diabetes as cause of CRF, coronary insufficiency and use of channel blockers calcium.

  20. Human factors in annunciation systems - Recommendations for a Canadian regulatory framework

    Energy Technology Data Exchange (ETDEWEB)

    Beattie, J D; Rochford, S; Vicente, K J [Humansystems Inc., ON (Canada)

    1997-09-01

    Under a contract with the Atomic Energy Control Board (AECB) of Canada, brief reviews were conducted of the annunciation systems in Canadian nuclear power plant control rooms; of regulatory practices in other countries and relevant international guidelines; and of the human factors literature related to annunciation systems. Based on these reviews, a framework is proposed for regulatory criteria which could be applied to new annunciation system designs. (author). 29 refs.

  1. Modularity, Integration and IT Personnel Skills Factors in Linking ERP to SCM Systems

    OpenAIRE

    Chung, Sock H; Tang, Hung-Lian; Ahmad, Imtiaz

    2011-01-01

    This study investigates some underlying technological factors for linking enterprise resource planning (ERP) to supply chain management (SCM) systems. ERP systems serve technological requirements across functional areas within a corporate boundary while SCM systems focus on collaborative relationships with partners in the supply chain, emphasizing business process integration and information sharing through IT. In order to facilitate SCM operations for business planning and decision making, a...

  2. Human factors in annunciation systems - Recommendations for a Canadian regulatory framework

    International Nuclear Information System (INIS)

    Beattie, J.D.; Rochford, S.; Vicente, K.J.

    1997-01-01

    Under a contract with the Atomic Energy Control Board (AECB) of Canada, brief reviews were conducted of the annunciation systems in Canadian nuclear power plant control rooms; of regulatory practices in other countries and relevant international guidelines; and of the human factors literature related to annunciation systems. Based on these reviews, a framework is proposed for regulatory criteria which could be applied to new annunciation system designs. (author). 29 refs

  3. Proceedings of the international topical meeting on advances in human factors in nuclear power systems

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    This book presents the papers given at a conference on the human factors engineering of nuclear power plants. Topics considered at the conference included human modeling, artificial intelligence, expert systems, robotics and teleoperations, organizational issues, innovative applications, testing and evaluation, training systems technology, a modeling framework for crew decisions during reactor accident sequences, intelligent operator support systems, control algorithms for robot navigation, and personnel management

  4. Critical success factors for implementing supply chain information systems : insights from the pork industry

    OpenAIRE

    Denolf, J.M.

    2014-01-01

    Critical success factors for implementing supply chain information systems – Janne M. Denolf Due to intensified competition, companies realize that they should closely collaborate with their supply-chain partners to further cut costs and stay competitive. To do so, supply-chain partners should intensify information sharing, which is often facilitated through supply chain information systems (SCIS). Implementation of such a system is a complex undertaking due to the umpteen technical and organ...

  5. Critical success factors in implementing an e-rostering system in a healthcare organisation.

    Science.gov (United States)

    Soomro, Zahoor A; Ahmed, Javed; Muhammad, Raza; Hayes, Dawn; Shah, Mahmood H

    2017-01-01

    Effective and efficient staff scheduling has always been a challenging issue, especially in health service organisations. Both the extremes of staff shortage and overage have an adverse impact on the performance of healthcare organisations. In this case, an electronic and systematic staff scheduling (e-rostering) system is the often seen as the best solution. Unless an organisation has an effective implementation of such a system, possible cost savings, efficiency, and benefits could be minimal. This study is aimed to research key success factors for the successful effective implementation of an electronic rostering system, especially at healthcare organisations. A case study research method was used to evaluate critical success factors for effectively implementing an e-rostering system. The data were collected through interviews and observations. The findings indicate that technical support, an effective policy, leadership, clear goals and objectives, gradual change, evidence of the advantages of the new system, senior management support, and effective communication are the critical success factors in implementing an e-rostering system in healthcare organisations. Prior to this study, no such factors were grounded in the current context, so this research would help in bridging the gap towards effective implementation of an e-rostering system in the healthcare sector. This research also suggests future studies in different cultures and contexts.

  6. Physical factors that influence patients’ privacy perception toward a psychiatric behavioral monitoring system: a qualitative study

    Science.gov (United States)

    Zakaria, Nasriah; Ramli, Rusyaizila

    2018-01-01

    Background Psychiatric patients have privacy concerns when it comes to technology intervention in the hospital setting. In this paper, we present scenarios for psychiatric behavioral monitoring systems to be placed in psychiatric wards to understand patients’ perception regarding privacy. Psychiatric behavioral monitoring refers to systems that are deemed useful in measuring clinical outcomes, but little research has been done on how these systems will impact patients’ privacy. Methods We conducted a case study in one teaching hospital in Malaysia. We investigated the physical factors that influence patients’ perceived privacy with respect to a psychiatric monitoring system. The eight physical factors identified from the information system development privacy model, a comprehensive model for designing a privacy-sensitive information system, were adapted in this research. Scenario-based interviews were conducted with 25 patients in a psychiatric ward for 3 months. Results Psychiatric patients were able to share how physical factors influence their perception of privacy. Results show how patients responded to each of these dimensions in the context of a psychiatric behavioral monitoring system. Conclusion Some subfactors under physical privacy are modified to reflect the data obtained in the interviews. We were able to capture the different physical factors that influence patient privacy. PMID:29343963

  7. Physical factors that influence patients' privacy perception toward a psychiatric behavioral monitoring system: a qualitative study.

    Science.gov (United States)

    Zakaria, Nasriah; Ramli, Rusyaizila

    2018-01-01

    Psychiatric patients have privacy concerns when it comes to technology intervention in the hospital setting. In this paper, we present scenarios for psychiatric behavioral monitoring systems to be placed in psychiatric wards to understand patients' perception regarding privacy. Psychiatric behavioral monitoring refers to systems that are deemed useful in measuring clinical outcomes, but little research has been done on how these systems will impact patients' privacy. We conducted a case study in one teaching hospital in Malaysia. We investigated the physical factors that influence patients' perceived privacy with respect to a psychiatric monitoring system. The eight physical factors identified from the information system development privacy model, a comprehensive model for designing a privacy-sensitive information system, were adapted in this research. Scenario-based interviews were conducted with 25 patients in a psychiatric ward for 3 months. Psychiatric patients were able to share how physical factors influence their perception of privacy. Results show how patients responded to each of these dimensions in the context of a psychiatric behavioral monitoring system. Some subfactors under physical privacy are modified to reflect the data obtained in the interviews. We were able to capture the different physical factors that influence patient privacy.

  8. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  9. Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two "fatigue" syndromes with overlapping symptoms and possibly related aetiologies.

    Science.gov (United States)

    Rovigatti, Ugo

    2012-12-01

    In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit. Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors. All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Modelling vital success factors in adopting personalized medicine system in healthcare technology and management

    Directory of Open Access Journals (Sweden)

    Subhas C. Misra

    2018-06-01

    Full Text Available Biomedical engineering has grown as a vast field of research that includes many areas of engineering and technology also. Personalized Medicine is an emerging approach in today’s medicare system. It bears a very strong potential to consolidate modern e-health systems fundamentally. Scientists have already discovered some of the personalized drugs that can shift the whole medicare system into a new dimension. However, bringing the change in the whole medicare system is not an easy task. There are several factors that can affect the successful adoption of Personalized Medicine systems in the healthcare management sector. This paper aims at identifying the critical factors with the help of an empirical study. A questionnaire was distributed amongst some clinicians, clinical researchers, practitioners in pharmaceutical industries, regulatory board members, and a larger section of patients. The response data collected thereby were analyzed by using appropriate statistical methods. Based on the statistical analysis, an attempt is made to prepare a list of critical success factors in the adoption of personalized medicine in healthcare management. The study indicates that eight of the thirteen hypothesized factors have statistical relationship with “Success”. The important success factors detected are: data management, team work and composition, privacy and confidentiality, mind-set, return on investment, sufficient time, R&D and alignment. To the best of our knowledge, this is the first academic paper in which an attempt has been made to model the vital critical factors for the successful implementation of Personalized Medicine in healthcare management. The study bears the promise of important applications in healthcare engineering and technology. Keywords: Healthcare management, Personalized medicine, E-health, Success factors, Medicare systems, Regression analysis

  11. Contributory factors in surgical incidents as delineated by a confidential reporting system.

    Science.gov (United States)

    Mushtaq, F; O'Driscoll, C; Smith, Fct; Wilkins, D; Kapur, N; Lawton, R

    2018-05-01

    Background Confidential reporting systems play a key role in capturing information about adverse surgical events. However, the value of these systems is limited if the reports that are generated are not subjected to systematic analysis. The aim of this study was to provide the first systematic analysis of data from a novel surgical confidential reporting system to delineate contributory factors in surgical incidents and document lessons that can be learned. Methods One-hundred and forty-five patient safety incidents submitted to the UK Confidential Reporting System for Surgery over a 10-year period were analysed using an adapted version of the empirically-grounded Yorkshire Contributory Factors Framework. Results The most common factors identified as contributing to reported surgical incidents were cognitive limitations (30.09%), communication failures (16.11%) and a lack of adherence to established policies and procedures (8.81%). The analysis also revealed that adverse events were only rarely related to an isolated, single factor (20.71%) - with the majority of cases involving multiple contributory factors (79.29% of all cases had more than one contributory factor). Examination of active failures - those closest in time and space to the adverse event - pointed to frequent coupling with latent, systems-related contributory factors. Conclusions Specific patterns of errors often underlie surgical adverse events and may therefore be amenable to targeted intervention, including particular forms of training. The findings in this paper confirm the view that surgical errors tend to be multi-factorial in nature, which also necessitates a multi-disciplinary and system-wide approach to bringing about improvements.

  12. Study of design factors of vehicle headlamp control systems; Zenshoto seigyo system no hyoka shuho no kento

    Energy Technology Data Exchange (ETDEWEB)

    Kamishima, H; Miwa, T; Sasaki, T; Imai, M [Nissan Motor Co. Ltd., Tokyo (Japan); Sumi, T [Niles Parts Co. Ltd., Tokyo (Japan)

    1997-10-01

    The on-and-off timing of vehicle headlamp control systems varies with weather conditions. Cloudy weather has a wider light energy distribution from visible to infrared radiation than clear weather. Silicon photodiodes, which can detect visible to infrared radiation, have larger output currents on cloudy evenings than on clear evenings under the same brightness conditions. The systems should be designed with such factors in mind as spectral characteristics of windshield, filters, sensor, and eyesight. 4 refs., 9 figs.

  13. An Item Bank to Measure Systems, Services, and Policies: Environmental Factors Affecting People With Disabilities.

    Science.gov (United States)

    Lai, Jin-Shei; Hammel, Joy; Jerousek, Sara; Goldsmith, Arielle; Miskovic, Ana; Baum, Carolyn; Wong, Alex W; Dashner, Jessica; Heinemann, Allen W

    2016-12-01

    To develop a measure of perceived systems, services, and policies facilitators (see Chapter 5 of the International Classification of Functioning, Disability and Health) for people with neurologic disabilities and to evaluate the effect of perceived systems, services, and policies facilitators on health-related quality of life. Qualitative approaches to develop and refine items. Confirmatory factor analysis including 1-factor confirmatory factor analysis and bifactor analysis to evaluate unidimensionality of items. Rasch analysis to identify misfitting items. Correlational and analysis of variance methods to evaluate construct validity. Community-dwelling individuals participated in telephone interviews or traveled to the academic medical centers where this research took place. Participants (N=571) had a diagnosis of spinal cord injury, stroke, or traumatic brain injury. They were 18 years or older and English speaking. Not applicable. An item bank to evaluate environmental access and support levels of services, systems, and policies for people with disabilities. We identified a general factor defined as "access and support levels of the services, systems, and policies at the level of community living" and 3 local factors defined as "health services," "community living," and "community resources." The systems, services, and policies measure correlated moderately with participation measures: Community Participation Indicators (CPI) - Involvement, CPI - Control over Participation, Quality of Life in Neurological Disorders - Ability to Participate, Quality of Life in Neurological Disorders - Satisfaction with Role Participation, Patient-Reported Outcomes Measurement Information System (PROMIS) Ability to Participate, PROMIS Satisfaction with Role Participation, and PROMIS Isolation. The measure of systems, services, and policies facilitators contains items pertaining to health services, community living, and community resources. Investigators and clinicians can measure

  14. Physical factors that influence patients’ privacy perception toward a psychiatric behavioral monitoring system: a qualitative study

    Directory of Open Access Journals (Sweden)

    Zakaria N

    2017-12-01

    Full Text Available Nasriah Zakaria,1,2 Rusyaizila Ramli3 1Research Chair of Health Informatics and Promotion, 2Medical Informatics and E-learning Unit, Medical Education Department, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Advanced Military Maintenance Repair and Overhaul Center (AMMROC, Abu Dhabi, UAE Background: Psychiatric patients have privacy concerns when it comes to technology intervention in the hospital setting. In this paper, we present scenarios for psychiatric behavioral monitoring systems to be placed in psychiatric wards to understand patients’ perception regarding privacy. Psychiatric behavioral monitoring refers to systems that are deemed useful in measuring clinical outcomes, but little research has been done on how these systems will impact patients’ privacy. Methods: We conducted a case study in one teaching hospital in Malaysia. We investigated the physical factors that influence patients’ perceived privacy with respect to a psychiatric monitoring system. The eight physical factors identified from the information system development privacy model, a comprehensive model for designing a privacy-sensitive information system, were adapted in this research. Scenario-based interviews were conducted with 25 patients in a psychiatric ward for 3 months. Results: Psychiatric patients were able to share how physical factors influence their perception of privacy. Results show how patients responded to each of these dimensions in the context of a psychiatric behavioral monitoring system. Conclusion: Some subfactors under physical privacy are modified to reflect the data obtained in the interviews. We were able to capture the different physical factors that influence patient privacy. Keywords: information system development (ISD, physical factor, privacy, psychiatric monitoring system

  15. Time Factor in the Theory of Anthropogenic Risk Prediction in Complex Dynamic Systems

    Science.gov (United States)

    Ostreikovsky, V. A.; Shevchenko, Ye N.; Yurkov, N. K.; Kochegarov, I. I.; Grishko, A. K.

    2018-01-01

    The article overviews the anthropogenic risk models that take into consideration the development of different factors in time that influence the complex system. Three classes of mathematical models have been analyzed for the use in assessing the anthropogenic risk of complex dynamic systems. These models take into consideration time factor in determining the prospect of safety change of critical systems. The originality of the study is in the analysis of five time postulates in the theory of anthropogenic risk and the safety of highly important objects. It has to be stressed that the given postulates are still rarely used in practical assessment of equipment service life of critically important systems. That is why, the results of study presented in the article can be used in safety engineering and analysis of critically important complex technical systems.

  16. Hybrid PV/diesel solar power system design using multi-level factor analysis optimization

    Science.gov (United States)

    Drake, Joshua P.

    Solar power systems represent a large area of interest across a spectrum of organizations at a global level. It was determined that a clear understanding of current state of the art software and design methods, as well as optimization methods, could be used to improve the design methodology. Solar power design literature was researched for an in depth understanding of solar power system design methods and algorithms. Multiple software packages for the design and optimization of solar power systems were analyzed for a critical understanding of their design workflow. In addition, several methods of optimization were studied, including brute force, Pareto analysis, Monte Carlo, linear and nonlinear programming, and multi-way factor analysis. Factor analysis was selected as the most efficient optimization method for engineering design as it applied to solar power system design. The solar power design algorithms, software work flow analysis, and factor analysis optimization were combined to develop a solar power system design optimization software package called FireDrake. This software was used for the design of multiple solar power systems in conjunction with an energy audit case study performed in seven Tibetan refugee camps located in Mainpat, India. A report of solar system designs for the camps, as well as a proposed schedule for future installations was generated. It was determined that there were several improvements that could be made to the state of the art in modern solar power system design, though the complexity of current applications is significant.

  17. Influence of physical factors on sexual function and pituitary gland-gonads system. Chapter 3

    International Nuclear Information System (INIS)

    2000-01-01

    In the Chapter 3 it is noted, that different physical factors even with low intensity (vibration, noise, electromagnetic oscillations of s.h.f. and u.h.f range, laser radiation, temperature changes) predictably lead to spermatogenesis dysfunctions and functional shift in hypothalamus-pituitary gland-gonads system with examined animals and man. The sexual function of men changing in the result of contact with unfavourable physical factors arise early and quite often they preceding the manifestation of occupational diseases pattern

  18. Structure of Political Success Factors as an Indicator of Political Direction in Electoral System Development

    OpenAIRE

    Panina, Nataliia

    2005-01-01

    The article presents a conceptual model of democratic electoral system development and analysis of empirical data on factors of political success in the electoral situation. Various participants of the electoral process (population, politicians, journalists, government employees, analysts-politologists) evaluated the political success factors; and comparative analysis of these evaluations made it possible to determine the main vectors (“reverse” and “manipulative-mystifying”) affecting deviat...

  19. Factors influencing intentions to use social recommender systems: a social exchange perspective.

    Science.gov (United States)

    Chang, Tsung-Sheng; Hsiao, Wei-Hung

    2013-05-01

    This study employs the perspective of social exchange theory and seeks to understand users' intentions to use social recommender systems (SRS) through three psychological factors: trust, shared values, and reputation. We use structural equation modeling to analyze 221 valid questionnaires. The results show that trust has a direct positive influence on the intention to use SRS, followed by shared values, whereas reputation has an indirect influence on SRS use. We further discuss specific recommendations concerning these factors for developing SRS.

  20. Factors Influencing the Job Satisfaction of Health System Employees in Tabriz, Iran

    OpenAIRE

    Bagheri, Shokoufe; Kousha, Ahmad; Janati, Ali; Asghari-Jafarabadi, Mohammad

    2012-01-01

    Background: Employees can be counseled on how they feel about their job. If any particular dimension of their job is causing them dissatisfaction, they can be assisted to appropriately change it. In this study, we investigated the factors affecting job satisfaction from the perspective of employees working in the health system and thereby a quantitative measure of job satisfaction.Methods: Using eight focus group discussions (n=70), factors affecting job satisfaction of the employees were dis...

  1. Motivational Factors Affecting the Integration of a Learning Management System by Faculty

    Directory of Open Access Journals (Sweden)

    Cynthia Gautreau

    2011-01-01

    Full Text Available Online courses taught using a learning management system are common in higher education. Teaching online requires a new set of skills, knowledge, and professional growth. Faculty development programs often overlook factors that promote or inhibit the use of technologies among professors. This study identified the motivation factors that faculty consider relevant to their personal decision to adopt a learning management system. A needs assessment evaluation methodology was applied to investigate two research questions. The first question analyzed the demographics of the participants in this study including gender, age, tenure status, department, and years of experience using a technology and using an LMS. The second research question investigated the intrinsic and extrinsic factors that motivate faculty to adopt a learning management system in their instruction. Participants (N = 42 were tenured and tenure track faculty instructing at a four-year public university in California.

  2. Specific factors influencing information system/information and communication technology sourcing strategies in healthcare facilities.

    Science.gov (United States)

    Potančok, Martin; Voříšek, Jiří

    2016-09-01

    Healthcare facilities use a number of information system/information and communication technologies. Each healthcare facility faces a need to choose sourcing strategies most suitable to ensure provision of information system/information and communication technology services, processes and resources. Currently, it is possible to observe an expansion of sourcing possibilities in healthcare informatics, which creates new requirements for sourcing strategies. Thus, the aim of this article is to identify factors influencing information system/information and communication technology sourcing strategies in healthcare facilities. The identification was based on qualitative research, namely, a case study. This study provides a set of internal and external factors with their impact levels. The findings also show that not enough attention is paid to these factors during decision-making. © The Author(s) 2015.

  3. Factors affecting the appreciation generated through applying human factors/ergonomics (HFE) principles to systems of work.

    Science.gov (United States)

    So, R H Y; Lam, S T

    2014-01-01

    This retrospective study examined the levels of appreciation (applause) given by clients to Human Factors/Ergonomic (HFE) specialists after they have modified the systems of work. Thirteen non-academic projects were chosen because the HFE interventions involved changed the way workers work at their workplaces. Companies involved range from multi-national corporations and military organizations with thousands of employees to small trading companies with less than 10 employees. In 5 cases the HFE recommendations were fully adopted and well appreciated. In 4 they were largely ignored and not appreciated, with partial adoption and some appreciation in the other 4 cases. Three factors that predict appreciation were identified: (i) alignment between the benefits HFE can provide and the project's key performance indices; (ii) awareness of HFE among the client's senior management; and (iii) a team organization appropriate for applying HFE recommendations. Having an HFE specialist on the client's side can greatly increase levels of appreciation, but lack of such a specialist will not affect levels of appreciation. A clear contractual requirement for HFE intervention does not promote appreciation significantly, but its absence can greatly reduce levels of appreciation. These relationships are discussed using the Kano's model of quality. Means to generate greater appreciation of the benefits of HFE are discussed. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  4. Implementing factors on finance information systems: How do they influence usage?

    Directory of Open Access Journals (Sweden)

    David Kiwana

    2018-04-01

    Full Text Available Finance information systems (FISs store and provide timely, accurate and consistent financial data for management and decision-making. Many organizations especially in developing world however fail to attain desired success during implementation and usage of the FISs despite the fact that many success factors for implementation have been suggested. This study thus investigated the usage of FISs with the aim of finding out how factors presumed to influence implementation impact usage. The presumed factors included; top management support, effective communication, evaluation of staff performance, technical support, project management, change management program, effectiveness of IT unit and flexibility of consultants. The study focused on universities in Uganda, which is a developing country. Out of the nine factors that were investigated only top management support, technical training and flexibility of consultants exhibited a positive impact with only top management support being significant. The rest of the factors exhibited negative impact and only effective IT unit being significant.

  5. System Dynamics Modeling of interactive cost factors for small modular reactors

    International Nuclear Information System (INIS)

    Ahn, Nam Sung; Lee, Keun Dae; Yoon, Suk Ho

    2011-01-01

    As a part of the Study on Economic Efficiency and Marketability of small modular reactors project, we at Nemo partners NEC consulting corporation were studying the various cost factors on small modular reactors (SMRs). To have a better knowledge of the interaction between the cost factors, System Dynamics Modeling has been developed. This model will contribute to our understanding of the interaction on the major factors effecting on the unit cost of SMRs to the SMRs' market share in the market economics as competition

  6. A quantitative assessment of organizational factors affecting safety using system dynamics model

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jae Kook; Ahn, Nam Sung [Korea Electric Power Research Institute, Taejon (Korea, Republic of); Jae, Moo Sung [Hanyang Univ., Seoul (Korea, Republic of)

    2004-02-01

    The purpose of this study is to develop a system dynamics model for the assessment of the organizational and human factors in a nuclear power plant which contribute to nuclear safety. Previous studies can be classified into two major approaches. One is the engineering approach using tools such as ergonomics and Probability Safety Assessment (PSA). The other is the socio-psychology approach. Both have contributed to find organizational and human factors and to present guidelines to lessen human error in plants. However, since these approaches assume that the relationship among factors is independent they do not explain the interactions among the factors or variables in nuclear power plants. To overcome these restrictions, a system dynamics model, which can show cause and effect relationships among factors and quantify the organizational and human factors, has been developed. Handling variables such as the degree of leadership, the number of employees, and workload in each department, users can simulate various situations in nuclear power plant organization. Through simulation, users can get insights to improve safety in plants and to find managerial tools in both organizational and human factors.

  7. A quantitative assessment of organizational factors affecting safety using system dynamics model

    International Nuclear Information System (INIS)

    Yu, Jae Kook; Ahn, Nam Sung; Jae, Moo Sung

    2004-01-01

    The purpose of this study is to develop a system dynamics model for the assessment of the organizational and human factors in a nuclear power plant which contribute to nuclear safety. Previous studies can be classified into two major approaches. One is the engineering approach using tools such as ergonomics and Probability Safety Assessment (PSA). The other is the socio-psychology approach. Both have contributed to find organizational and human factors and to present guidelines to lessen human error in plants. However, since these approaches assume that the relationship among factors is independent they do not explain the interactions among the factors or variables in nuclear power plants. To overcome these restrictions, a system dynamics model, which can show cause and effect relationships among factors and quantify the organizational and human factors, has been developed. Handling variables such as the degree of leadership, the number of employees, and workload in each department, users can simulate various situations in nuclear power plant organization. Through simulation, users can get insights to improve safety in plants and to find managerial tools in both organizational and human factors

  8. A computational intelligent approach to multi-factor analysis of violent crime information system

    Science.gov (United States)

    Liu, Hongbo; Yang, Chao; Zhang, Meng; McLoone, Seán; Sun, Yeqing

    2017-02-01

    Various scientific studies have explored the causes of violent behaviour from different perspectives, with psychological tests, in particular, applied to the analysis of crime factors. The relationship between bi-factors has also been extensively studied including the link between age and crime. In reality, many factors interact to contribute to criminal behaviour and as such there is a need to have a greater level of insight into its complex nature. In this article we analyse violent crime information systems containing data on psychological, environmental and genetic factors. Our approach combines elements of rough set theory with fuzzy logic and particle swarm optimisation to yield an algorithm and methodology that can effectively extract multi-knowledge from information systems. The experimental results show that our approach outperforms alternative genetic algorithm and dynamic reduct-based techniques for reduct identification and has the added advantage of identifying multiple reducts and hence multi-knowledge (rules). Identified rules are consistent with classical statistical analysis of violent crime data and also reveal new insights into the interaction between several factors. As such, the results are helpful in improving our understanding of the factors contributing to violent crime and in highlighting the existence of hidden and intangible relationships between crime factors.

  9. Consideration for solar system exploration - A system to Mars. [biomedical, environmental, and psychological factors

    Science.gov (United States)

    Nicogossian, Arnauld E.; Garshnek, Victoria

    1989-01-01

    Biomedical issues related to a manned mission to Mars are reviewed. Consideration is given to cardiovascular deconditioning, hematological and immunological changes, bone and muscle changes, nutritional issues, and the development of physiological countermeasures. Environmental issues are discussed, including radiation hazards, toxic chemical exposure, and the cabin environment. Also, human factors, performance and behavior, medical screening of the crew, disease prediction, and health maintenance are examined.

  10. Human factors and systems engineering approach to patient safety for radiotherapy.

    Science.gov (United States)

    Rivera, A Joy; Karsh, Ben-Tzion

    2008-01-01

    The traditional approach to solving patient safety problems in healthcare is to blame the last person to touch the patient. But since the publication of To Err is Human, the call has been instead to use human factors and systems engineering methods and principles to solve patient safety problems. However, an understanding of the human factors and systems engineering is lacking, and confusion remains about what it means to apply their principles. This paper provides a primer on them and their applications to patient safety.

  11. Cyberknife Relative Output Factor measurements using fiber-coupled luminescence, MOSFETS and RADPOS dosimetry system

    DEFF Research Database (Denmark)

    Ploquin, N.; Kertzscher Schwencke, Gustavo Adolfo Vladimir; Vandervoort, E.

    2012-01-01

    from 5 to 60 mm. ROFs were also measured using a mobileMOSFET system (Best Medical Canada) and EBT1 and EBT2 GAFCHROMIC® (ISP, Ashland) radiochromic films. For cone sizes 12.5–60 mm all detector results were in agreement within the measurement uncertainty. The microMOSFET/RADPOS measurements (published.......3% and 0.865 ± 0.3% for 5, 7.5 and 10 mm cones. Our study shows that the microMOSFET/RADPOS and optical fiber‐coupled RL dosimetry system are well suited for Cyberknife cone output factors measurements over the entire range of field sizes, provided that appropriate correction factors are applied...

  12. Human Factors and Systems Engineering Approach to Patient Safety for Radiotherapy

    International Nuclear Information System (INIS)

    Rivera, A. Joy; Karsh, Ben-Tzion

    2008-01-01

    The traditional approach to solving patient safety problems in healthcare is to blame the last person to touch the patient. But since the publication of To Err is Human, the call has been instead to use human factors and systems engineering methods and principles to solve patient safety problems. However, an understanding of the human factors and systems engineering is lacking, and confusion remains about what it means to apply their principles. This paper provides a primer on them and their applications to patient safety

  13. EFFECTIVE FACTORS AND MODEL SYSTEMS IN THE INDUSTRIAL PRODUCTION OF NISIN

    Directory of Open Access Journals (Sweden)

    Ömer ŞİMŞEK

    2007-01-01

    Full Text Available Nisin is the first bacteriocin identified in Lactococcus lactis and belongs to type 1 lanthibiotic group. High nisin production in cultured media is related with the composition of fermentation medium, pH, produced nisin concentration and most importantly growth amount of cell. For industrial purpose, batch, fed-batch and continue fermentation systems were developed by regarding these factors. Maintaining efficient production of nisin having important potential at preservation of foods is important for both industrial production and using as starter culture. In this review the fermentation factors at nisin production were outlined and constructed model systems were compared.

  14. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    Science.gov (United States)

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  15. Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats.

    Directory of Open Access Journals (Sweden)

    Nicholas W Gilpin

    Full Text Available Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (~postnatal days 28-42 in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF cell in the lateral portion of the central amygdala (CeA, a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity, an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects

  16. A systems biology perspective on the role of WRKY transcription factors in drought responses in plants.

    Science.gov (United States)

    Tripathi, Prateek; Rabara, Roel C; Rushton, Paul J

    2014-02-01

    Drought is one of the major challenges affecting crop productivity and yield. However, water stress responses are notoriously multigenic and quantitative with strong environmental effects on phenotypes. It is also clear that water stress often does not occur alone under field conditions but rather in conjunction with other abiotic stresses such as high temperature and high light intensities. A multidisciplinary approach with successful integration of a whole range of -omics technologies will not only define the system, but also provide new gene targets for both transgenic approaches and marker-assisted selection. Transcription factors are major players in water stress signaling and some constitute major hubs in the signaling webs. The main transcription factors in this network include MYB, bHLH, bZIP, ERF, NAC, and WRKY transcription factors. The role of WRKY transcription factors in abiotic stress signaling networks is just becoming apparent and systems biology approaches are starting to define their places in the signaling network. Using systems biology approaches, there are now many transcriptomic analyses and promoter analyses that concern WRKY transcription factors. In addition, reports on nuclear proteomics have identified WRKY proteins that are up-regulated at the protein level by water stress. Interactomics has started to identify different classes of WRKY-interacting proteins. What are often lacking are connections between metabolomics, WRKY transcription factors, promoters, biosynthetic pathways, fluxes and downstream responses. As more levels of the system are characterized, a more detailed understanding of the roles of WRKY transcription factors in drought responses in crops will be obtained.

  17. Human factors, system safety, and systems engineering in the transportation of U.S. high-level waste

    International Nuclear Information System (INIS)

    Price, D.L.; Chu, S.C.

    1993-01-01

    The U.S. Nuclear Waste Technical Review Board is an independent agency charged with evaluating the technical and scientific validity of the U.S. Department of Energy's program to manage the disposal of spent fuel and defense high-level waste. The Board has continued to emphasize the importance of using a true system approach in designing the waste management system. The Board has recommended the application of basic design disciplines such as human factors, system safety, and systems engineering. A top-level system study needs to be undertaken that focuses on minimizing handling. The analysis must be well done, in a timely manner, and without the inclusion in the analysis of arbitrary and artificial constraints. (author)

  18. Factors Influencing the Job Satisfaction of Health System Employees in Tabriz, Iran

    Directory of Open Access Journals (Sweden)

    Shokoufe Bagheri

    2012-12-01

    Full Text Available Background: Employees can be counseled on how they feel about their job. If any particular dimension of their job is causing them dissatisfaction, they can be assisted to appropriately change it. In this study, we investigated the factors affecting job satisfaction from the perspective of employees working in the health system and thereby a quantitative measure of job satisfaction.Methods: Using eight focus group discussions (n=70, factors affecting job satisfaction of the employees were discussed. The factors identified from literature review were categorized in four groups: structural and managerial, social, work in it-self, environmental and welfare factors.Results: The findings confirmed the significance of structural and managerial, social, work in it-self, environmental and welfare factors in the level of job satisfaction. In addition, a new factor related to individual characteristics such as employee personal characteristics and development was identified.Conclusion: In order to improve the quality and productivity of work, besides, structural and managerial, social, work in it-self, environmental and welfare factors, policy makers should be taken into account individual characteristics of the employee as a factor affecting job satisfaction.

  19. Factors influencing the job satisfaction of health system employees in tabriz, iran.

    Science.gov (United States)

    Bagheri, Shokoufe; Kousha, Ahmad; Janati, Ali; Asghari-Jafarabadi, Mohammad

    2012-01-01

    Employees can be counseled on how they feel about their job. If any particular dimension of their job is causing them dissatisfaction, they can be assisted to appropriately change it. In this study, we investigated the factors affecting job satisfaction from the perspective of employees working in the health system and thereby a quantitative measure of job satisfaction. Using eight focus group discussions (n=70), factors affecting job satisfaction of the employees were discussed. The factors identified from literature review were categorized in four groups: structural and managerial, social, work in it-self, environmental and welfare factors. The findings confirmed the significance of structural and managerial, social, work in it-self, environmental and welfare factors in the level of job satisfaction. In addition, a new factor related to individual characteristics such as employee personal characteristics and development was identified. In order to improve the quality and productivity of work, besides, structural and managerial, social, work in it-self, environmental and welfare factors, policy makers should be taken into account individual characteristics of the employee as a factor affecting job satisfaction.

  20. Platelet-derived growth factor-C and -D in the cardiovascular system and diseases.

    Science.gov (United States)

    Lee, Chunsik; Li, Xuri

    2018-08-01

    The cardiovascular system is among the first organs formed during development and is pivotal for the formation and function of the rest of the organs and tissues. Therefore, the function and homeostasis of the cardiovascular system are finely regulated by many important molecules. Extensive studies have shown that platelet-derived growth factors (PDGFs) and their receptors are critical regulators of the cardiovascular system. Even though PDGF-C and PDGF-D are relatively new members of the PDGF family, their critical roles in the cardiovascular system as angiogenic and survival factors have been amply demonstrated. Understanding the functions of PDGF-C and PDGF-D and the signaling pathways involved may provide novel insights into both basic biomedical research and new therapeutic possibilities for the treatment of cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Factors affecting management accounting and control systems. A critical review of empirical studies

    Directory of Open Access Journals (Sweden)

    Joanna Dyczkowska

    2015-12-01

    Full Text Available Knowledge of management accounting & control systems and factors which may affect the design of such systems has become crucial due to emerging changes both in the external and internal business environment. Therefore it is necessary to conduct comprehensive, long-term basic research in order to prove previously formulated hypotheses in new conditions and fulfil the research gap. Based on critical review of empirical studies published in prestigious scientific journals this paper aims at validating the assumed hypotheses and at generalising research findings on impacts of various determinants on man-agement accounting & control systems. The predominant contingent factors include: type of strategy implemented, national culture, perceived environment uncertainty and integrated information system.

  2. Effects off system factors on the economics of and demand for small solar thermal power systems

    Science.gov (United States)

    1981-09-01

    Market penetration as a function time, SPS performance factors, and market/economic considerations was estimated, and commercialization strategies were formulated. A market analysis task included personal interviews and supplemental mail surveys to acquire statistical data and to identify and measure attitudes, reactions and intentions of prospective SPS users. Interviews encompassed three ownership classes of electric utilities and industrial firms in the SIC codes for energy consumption. A market demand model was developed which utilized the data base developed, and projected energy price and consumption data to perform sensitivity analyses and estimate potential market for SPS.

  3. Factors influencing the performance and efficiency of solar water pumping systems:  a review

    OpenAIRE

    Gouws, Rupert; Lukhwareni, Thendo

    2012-01-01

    The world is having an energy crisis and currently there is a strong drive towards renewable energy. A renewable energy option is solar energy, where by means of photovoltaic (PV) modules electrical energy can be produced. A residential as well as industrial application for these PV modules is solar water pumping systems. Disadvantages of solar water pumping systems are low performance and low energy efficiency. This paper provides a review on the factors that influence the performance and ef...

  4. Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis.

    Science.gov (United States)

    Ziemann, Alexandra; Fouillet, Anne; Brand, Helmut; Krafft, Thomas

    2016-01-01

    Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings.

  5. A 3-Factor Model Relating Communication to Risk Mitigation of Extended Information System Failover

    Directory of Open Access Journals (Sweden)

    Athanasios Podaras

    2015-06-01

    Full Text Available This paper aims to analyse the relation between timely and effective communication and risk mitigation of late recovery after an unexpected information system outage in enterprises. An unforeseen information system failure in modern enterprise units, may result to significant operational and financial damage. In such a critical incident, effective communication between the team leaders and the recovery team involved, can minimize or even eliminate this negative impact. An extended information system outage can be perceived as a time deviation from the Maximum Accepted Outage (ΜΑΟ timeframe, proposed by the business continuity management, according to the value of which dependent business functions may be interrupted without any serious effects to the company. The paper examines the relation between 3 basic factors and the efficient communication between team members. The factors are: timely information distribution, staff availability and network availability. Through the current paper, the author proposes a risk analysis model, based on the Composite Risk Index theory of Risk Management, which can significantly diminish the possibility of an extended information system outage, as well as calculate the extended time required to recover a system when the aforementioned factors emerge in their worst form. The precise calculation of recovery time can be achieved via the execution of business continuity tests which include scenarios, according to which an unexpected system outage coexists with delayed information distribution as well as low staff and network availability.

  6. Decomposition of Factors and Criteria for Evaluating the Process of Intellectualization of Enterprise Management Systems

    Directory of Open Access Journals (Sweden)

    Kuzmin Oleh Ye.

    2017-03-01

    Full Text Available The article presents the author’s vision of solving the scientific problem of determining factors of influence and forming criteria for evaluating the process of intellectualization of enterprise management systems. It is found that diagnostic evaluation of the process of intellectualization of enterprise management systems depends on the influence of factors of the internal environment of the management systems, personal motivation factors, and the external environment. There carried out decomposition of the process of intellectualization of management systems into separate constituents and group criteria for diagnosing and their detailed indicators are selected. The basic group criteria for evaluating the process of intellectualization of management systems include: knowledge potential of carriers of intelligence; human capital; intellectual competence level of the management personnel; motivation of carriers of intelligence; state of the management development; scientific and research potential; development of information and communication technologies; intellectual and economic activity; formation of intellectual capital; institutional development of the management system, formation of knowledge and innovation prospects; complexity of the intellectualization process.

  7. Human factors certification in the development of future air traffic control systems

    Science.gov (United States)

    Evans, Alyson E.

    1994-01-01

    If human factors certification of aviation technologies aims to encompass the wide range of issues which need to be addressed for any new system, then human factors involvement must be present throughout the whole design process in a manner which relates to final certification. A certification process cannot simply be applied to the final product of design. Standards and guidelines will be required by designers at the outset of design for reference in preparing for certification. The most effective use of human factors principles, methods, and measures is made as part of an iterative design process, leading to a system which reflects these as far as possible. This particularly applies where the technology is complex and may be represented by a number of components or sub-systems. Some aspects of the system are best certified during early prototyping, when there is still scope to make changes to software or hardware. At this stage in design, financial and/or time pressures will not rule out the possibility of necessary changes, as may be the case later. Other aspects of the system will be best certified during the final phases of design when the system is in a more complete form and in a realistic environment.

  8. A quantitative assessment of organizational factors affecting safety using a system dynamics model

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, J. K. [Systemix Company, Seoul (Korea, Republic of); Yoon, T. S. [Korea Electric Power Research Institute (Korea, Republic of)

    2003-07-01

    The purpose of this study is to develop a system dynamics model for the assessment of organizational and human factors in the nuclear power plant safety. Previous studies are classified into two major approaches. One is the engineering approach such as ergonomics and Probabilistic Safety Assessment (PSA). The other is socio-psychology one. Both have contributed to find organizational and human factors and increased nuclear safety However, since these approaches assume that the relationship among factors is independent they do not explain the interactions between factors or variables in NPP's. To overcome these restrictions, a system dynamics model, which can show causal relations between factors and quantify organizational and human factors, has been developed. Operating variables such as degree of leadership, adjustment of number of employee, and workload in each department, users can simulate various situations in nuclear power plants in the organization side. Through simulation, user can get an insight to improve safety in plants and to find managerial tools in the organization and human side.

  9. A quantitative assessment of organizational factors affecting safety using a system dynamics model

    International Nuclear Information System (INIS)

    Yoo, J. K.; Yoon, T. S.

    2003-01-01

    The purpose of this study is to develop a system dynamics model for the assessment of organizational and human factors in the nuclear power plant safety. Previous studies are classified into two major approaches. One is the engineering approach such as ergonomics and Probabilistic Safety Assessment (PSA). The other is socio-psychology one. Both have contributed to find organizational and human factors and increased nuclear safety However, since these approaches assume that the relationship among factors is independent they do not explain the interactions between factors or variables in NPP's. To overcome these restrictions, a system dynamics model, which can show causal relations between factors and quantify organizational and human factors, has been developed. Operating variables such as degree of leadership, adjustment of number of employee, and workload in each department, users can simulate various situations in nuclear power plants in the organization side. Through simulation, user can get an insight to improve safety in plants and to find managerial tools in the organization and human side

  10. Understanding Interactions between Hydrogeologic Factors, Design Variables, and System Operations for Multi-Well Aquifer Storage and Recovery Systems

    Science.gov (United States)

    Majumdar, S.; Miller, G. R.; Smith, B.; Sheng, Z.

    2017-12-01

    Aquifer Storage and Recovery (ASR) system is a powerful tool for managing our present and future freshwater supplies. It involves injection of excess water into an aquifer, storing and later recovering it when needed, such as in a drought or during peak demand periods. Multi-well ASR systems, such as the Twin Oaks Facility in San Antonio, consist of a group of wells that are used for simultaneous injection and extraction of stored water. While significant research has gone into examining the effects of hydraulic and operational factors on recovery efficiency for single ASR well, little is known about how multi-well systems respond to these factors and how energy uses may vary. In this study, we created a synthetic ASR model in MODFLOW to test a range of multi-well scenarios. We altered design parameters (well spacing, pumping capacity, well configuration), hydrogeologic factors (regional hydraulic gradient, hydraulic conductivity, dispersivity), and operational variables (injection and withdrawal durations; pumping rates) to determine the response of the system across a realistic range of interrelated parameters. We then computed energy use for each simulation, based on the hydraulic head in each well and standard pump factors, as well as recovery efficiency, based on tracer concentration in recovered water from the wells. The tracer concentration in the groundwater was determined using MT3DMS. We observed that the recovery and energy efficiencies for the Multi-well ASR system decrease with the increase in well spacing and hydraulic gradient. When longitudinal dispersivity was doubled, the recovery and energy efficiencies were nearly halved. Another finding from our study suggests that we can recover nearly 90% of the water after two successive cycles of operation. The results will be used to develop generalized operational guidelines for meeting freshwater demands and also optimise the energy consumed during pumping.

  11. Glycans Flanking the Hypervariable Connecting Peptide between the A and B Strands of the V1/V2 Domain of HIV-1 gp120 Confer Resistance to Antibodies That Neutralize CRF01_AE Viruses

    Science.gov (United States)

    O’Rourke, Sara M.; Sutthent, Ruengpung; Phung, Pham; Mesa, Kathryn A.; Frigon, Normand L.; To, Briana; Horthongkham, Navin; Limoli, Kay; Wrin, Terri; Berman, Phillip W.

    2015-01-01

    Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01_AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partially successful RV144 HIV vaccine trial, where the two CRF01_AE immunogens (derived from the A244 and TH023 isolates) both possessed glycosylation sites at N136 and N149. PMID:25793890

  12. Risk factor assessment and counselling for 12 months reduces metabolic and cardiovascular risk in overweight or obese patients with schizophrenia spectrum disorders: The CRESSOB study.

    Science.gov (United States)

    Gutiérrez-Rojas, Luis; Pulido, Susana; Azanza, Jose R; Bernardo, Miguel; Rojo, Luis; Mesa, Francisco J; Martínez-Ortega, Jose M

    2016-01-01

    Metabolic syndrome (MS) and cardiovascular risk factors (CRF) have been associated with patients with schizophrenia. The main objective is to assess the evolution of CRF and prevalence of MS for 12 months in a cohort of overweight patients diagnosed with schizophrenia schizophreniform disorder or schizoaffective disorder in which the recommendations for the assessment and control of metabolic and cardiovascular risk were applied. The Control of Metabolic and Cardiovascular Risk in Patients with Schizophrenia and Overweight (CRESSOB) study is a 12-month, observational, prospective, open-label, multicentre, naturalistic study including 109 community mental health clinics of Spain. The study included a total of 403 patients, of whom we could collect all variables related to CRF and MS in 366 patients. Of these 366 patients, 286 completed the follow-up, (baseline, months 3, 6 and 12) where they underwent a complete physical examination and a blood test (glucose, cholesterol and triglycerides), they were asked about their health-related habits (smoking, diet and exercise) and they were given a series of recommendations to prevent cardiovascular risk and MS. A total of 403 patients were included, 63% men, mean age (mean; (SD)) 40.5 (10.5) years. After 12 months, the study showed statistically significant decrease in weight (prisk of heart disease at 10 years (p=0.0353). Overweight patients with schizophrenia who receive appropriate medical care, including CRF monitoring and control of health-related habits experience improvements with regard to most CRFs.

  13. Project PANK: Rationale, study protocol and baseline results of a multidisciplinary school based intervention in children with cardiovascular and metabolic risk factors

    Directory of Open Access Journals (Sweden)

    Rui Batalau

    2017-05-01

    Full Text Available Abstract Aims: Cardiovascular disease risk factors occur more frequently in children with obesity. Project PANK is a multidisciplinary school-based intervention lasting 6 months to improve BMI z-score, waist circumference (WC, waist-to-height ratio (WHtR, blood pressure (BP, nutrition, physical activity (PA, sedentary behaviour (SB, cardiorespiratory fitness (CRF, glucose, cholesterol, and triglycerides (TG. Methods/DesignA total of 77 children (7-10 years were recruited from an urban school. The protocol includes PA and SB individual meetings for children/parents; increasing school exercise; PA and SB lessons for children; A goal in the number of steps/day to accomplish in and after school. In nutrition, the protocol includes three individual meetings for children/parents and six lessons for children. ResultsPositive associations were found between the BMI Z-score, WC, and WHtR with TG; the BMI Z-score and WHtR with glucose; the light PA time and HDL-C; the vigorous and moderate-to-vigorous PA with CRF; the caloric intake and lipids with LDL-C, BMI z-score, WC, and WHtR. A negative association was found between CRF and TG. ConclusionBaseline results stress the importance of multidisciplinary school-based interventions. We hypothesized that PANK will improve blood variables, anthropometric measures, and BP, by changing food intake, enhancing PA and CRF, and decreasing SB.

  14. Form factor of relativistic two-particle system and covariant hamiltonian formulation of quantum field theory

    International Nuclear Information System (INIS)

    Skachkov, N.; Solovtsov, I.

    1979-01-01

    Based on the hamiltonian formulation of quantum field theory proposed by Kadyshevsky the three-dimensional relativistic approach is developed for describing the form factors of composite systems. The main features of the diagram technique appearing in the covariant hamiltonian formulation of field theory are discussed. The three-dimensional relativistic equation for the vertex function is derived and its connection with that for the quasipotential wave function is found. The expressions are obtained for the form factor of the system through equal-time two-particle wave functions both in momentum and relativistic configurational representations. An explicit expression for the form factor is found for the case of two-particle interaction through the Coulomb potential

  15. Factors influencing workers to follow food safety management systems in meat plants in Ontario, Canada.

    Science.gov (United States)

    Ball, Brita; Wilcock, Anne; Aung, May

    2009-06-01

    Small and medium sized food businesses have been slow to adopt food safety management systems (FSMSs) such as good manufacturing practices and Hazard Analysis Critical Control Point (HACCP). This study identifies factors influencing workers in their implementation of food safety practices in small and medium meat processing establishments in Ontario, Canada. A qualitative approach was used to explore in-plant factors that influence the implementation of FSMSs. Thirteen in-depth interviews in five meat plants and two focus group interviews were conducted. These generated 219 pages of verbatim transcripts which were analysed using NVivo 7 software. Main themes identified in the data related to production systems, organisational characteristics and employee characteristics. A socio-psychological model based on the theory of planned behaviour is proposed to describe how these themes and underlying sub-themes relate to FSMS implementation. Addressing the various factors that influence production workers is expected to enhance FSMS implementation and increase food safety.

  16. Community characteristics and implementation factors associated with effective systems of care.

    Science.gov (United States)

    Lunn, Laurel M; Heflinger, Craig Anne; Wang, Wei; Greenbaum, Paul E; Kutash, Krista; Boothroyd, Roger A; Friedman, Robert M

    2011-07-01

    How are characteristics of communities associated with the implementation of the principles of systems of care (SOC)? This study uses multilevel modeling with a stratified random sample (N = 225) of US counties to explore community-level predictors of the implementation factors of the System of Care Implementation Survey. A model composed of community-level social indicators fits well with 5 of 14 factors identified as relevant for effective SOCs. As hypothesized, community disadvantage was negatively and residential stability positively associated with the implementation of SOC principles. Designation as a mental health professional shortage area was positively related to some implementation scores, as was the percentage of minority residents, while rurality was not significantly associated with any of the factors. Given the limitations of the study, the results should be interpreted with caution, but suggest that further research is merited to clarify these relationships that could inform efforts directed at promoting SOCs.

  17. International classifications of accounting systems as a result of influence of various environmental factors

    Directory of Open Access Journals (Sweden)

    Ivo Mijoč

    2012-12-01

    Full Text Available Activities of various environmental factors resulted in the emergence of accounting clusters that in- clude equal or similar countries, observed through evaluation (measurement criteria and publishing, which has led to group formation, i.e. clusterisation of accounting systems within similar or equal groups, subgroups and clusters. The key principle of group formation of accounting systems within certain clusters implies similar accounting practices, primarily the practice of measuring (evaluating positions and publishing information in financial reports. The measurement level and the quantity of published information is related to the environmental factors, primarily to cultural heritage, which, according to claims of numerous authors, is of crucial importance. If accounting practices of the com- pared countries are observed according to this factor, then it is possible to form at least two or more clusters, which is significant in the world of financial reporting as there are some controversies in the relation between IASB and FASB even today.

  18. Factors affecting the sustainability of solid waste management system-the case of Palestine.

    Science.gov (United States)

    Al-Khateeb, Ammar J; Al-Sari, Majed I; Al-Khatib, Issam A; Anayah, Fathi

    2017-02-01

    Understanding the predictors of sustainability in solid waste management (SWM) systems can significantly contribute to eliminate many waste management problems. In this paper, the sustainability elements of SWM systems of interest are (1) attitudes toward separation at the source, (2) behaviour regarding reuse and/or recycling and (3) willingness to pay for an improved service of SWM. The predictors affecting these three elements were studied in two Palestinian cities: Ramallah and Jericho. The data were collected via structured questionnaires and direct interviews with the respondents, and the analysis utilized a logistic regression model. The results showed that the place of residence and dwelling premises are the significant factors influencing attitudes toward separation at the source; the place of residence and age are the significant factors explaining behaviour regarding reuse and/or recycling; while the dwelling premises, gender, level of education and being received education on waste management are the significant factors affecting willingness to pay for an improved service of SWM.

  19. ERP system implementation costs and selection factors of an implementation approach

    DEFF Research Database (Denmark)

    Johansson, Björn; Sudzina, Frantisek; Newman, Mike

    2011-01-01

    , which influence the implementation approach in an ERP project, cause also an increase of the project cost in a European context? Our survey was conducted in Denmark, Slovakia and Slovenia and focused on this issue. Our main findings are that: 1) the number of implemented modules influences selection......Different approaches on implementation of enterprise resource planning (ERPs) systems exist. In this article, we investigate relationship between factors influencing selection of implementation approach and companies' ability to stay within budget when implementing ERPs. The question is: do factors...... of an implementation approach; 2) companies with information strategies are more likely to stay within budget regarding ERP systems implementation. However, we also found that: 3) implementation approach does not significantly influence ability to stay within budget; 4) a clear relationship between factors influencing...

  20. Curtailment in a Highly Renewable Power System and Its Effect on Capacity Factors

    Directory of Open Access Journals (Sweden)

    Alexander Kies

    2016-06-01

    Full Text Available The capacity factor of a power plant is the ratio of generation over its potential generation. It is an important measure to describe wind and solar resources. However, the fluctuating nature of renewable power generation makes it difficult to integrate all generation at times. Whenever generation exceeds the load, curtailment or storage of energy is required. With increasing renewable shares in the power system, the level of curtailment will further increase. In this work, the influence of the curtailment on the capacity factors for a highly renewable German power system is studied. An effective capacity factor is introduced, and the implications for the distribution of renewable power plants are discussed. Three years of highly-resolved weather data were used to model wind and solar power generation. Together with historical load data and a transmission model, a possible future German power system was simulated. It is shown that effective capacity factors for unlimited transmission are strongly reduced by up to 60% (wind and 70% (photovoltaics and therefore of limited value in a highly renewable power system. Furthermore, the results demonstrate that wind power benefits more strongly from a reinforced transmission grid than photovoltaics (PV does.

  1. Environmental Factors Affecting Computer Assisted Language Learning Success: A Complex Dynamic Systems Conceptual Model

    Science.gov (United States)

    Marek, Michael W.; Wu, Wen-Chi Vivian

    2014-01-01

    This conceptual, interdisciplinary inquiry explores Complex Dynamic Systems as the concept relates to the internal and external environmental factors affecting computer assisted language learning (CALL). Based on the results obtained by de Rosnay ["World Futures: The Journal of General Evolution", 67(4/5), 304-315 (2011)], who observed…

  2. Analysis Testing of Sociocultural Factors Influence on Human Reliability within Sociotechnical Systems: The Algerian Oil Companies

    Directory of Open Access Journals (Sweden)

    Abdelbaki Laidoune

    2016-09-01

    Conclusion: The explored sociocultural factors influence the human reliability both in qualitative and quantitative manners. The proposed model shows how reliability can be enhanced by some measures such as experience feedback based on, for example, safety improvements, training, and information. With that is added the continuous systems improvements to improve sociocultural reality and to reduce negative behaviors.

  3. Critical Success Factors for Adoption of Web-Based Learning Management Systems in Tanzania

    Science.gov (United States)

    Lwoga, Edda Tandi

    2014-01-01

    This paper examines factors that predict students' continual usage intention of web-based learning content management systems in Tanzania, with a specific focus at Muhimbili University of Health and Allied Science (MUHAS). This study sent a questionnaire surveys to 408 first year undergraduate students, with a rate of return of 66.7. This study…

  4. Organizational Factors and the Implementation of Family to Family: Contextual Elements of Systems Reform

    Science.gov (United States)

    Crea, Thomas M.; Crampton, David S.; Knight, Nelson; Paine-Wells, Lisa

    2011-01-01

    In efforts to reform the child welfare system, agency leaders must involve staff at all levels; yet, little research has been done to determine which organizational factors encourage or inhibit staff engagement. Employees from an urban child welfare agency were invited to complete a survey regarding organizational effectiveness and its influence…

  5. Influences of lifestyle factors on cardiac autonomic nervous system activity over time

    NARCIS (Netherlands)

    Hu, Mandy Xian; Lamers, Femke; de Geus, Eco J C; Penninx, Brenda W J H

    Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in

  6. Critical success factors for implementing supply chain information systems : insights from the pork industry

    NARCIS (Netherlands)

    Denolf, J.M.

    2014-01-01

    Critical success factors for implementing supply chain information systems – Janne M. Denolf

    Due to intensified competition, companies realize that they should closely collaborate with their supply-chain partners to further cut costs and stay competitive. To do so,

  7. Towards a framework of critical success factors for implementing supply-chain information systems

    NARCIS (Netherlands)

    Denolf, J.M.; Wognum, P.M.; Trienekens, J.H.; Vorst, van der J.G.A.J.; Omta, S.W.F.

    2015-01-01

    Supply chain information systems (SCISs) have emerged as the core of successful management in supply chains. However, the difficulties of SCIS implementations have been widely cited in the literature. Research on the critical success factors (CSFs) for SCIS implementation is rather scarce and

  8. An Empirical Examination of Factors Affecting Group Effectiveness in Information Systems Projects

    Science.gov (United States)

    Hasan, Bassam; Ali, Jafar

    2007-01-01

    Although group project concepts and skills have become a major component in most information systems (IS) academic programs, very little research has attempted to examine factors that may improve or undermine effectiveness of IS group projects. Accordingly, based on relevant literatures, this study develops and empirically tests a model of factors…

  9. Human factors study of driver assistance systems to reduce lane departures and side collision accidents.

    Science.gov (United States)

    2008-07-01

    This study investigated the human factors issues related to the implementation of lane departure warning systems (LDWS) to reduce side collision and run-off-road crashes for heavy trucks. Lane departures can be either intentional (e.g., to pass anoth...