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Sample records for substances specifically modulate

  1. Tumour imaging with non specific substances

    International Nuclear Information System (INIS)

    Pompe, W.B. van der.

    1978-01-01

    A short introduction concerning tumour imaging in nuclear medicine is given as well as the formulation of the problem treated in this thesis. In a literature review the most important tumour imaging radiopharmaceuticals used until now are described together with their clinical significance in the diagnosis of malignancy. The mechanism of uptake and subcellular distribution of most of the radiopharmaceuticals reviewed are discussed in chapter three with special reference to gallium-citrate. An ionic model to explain the distribution patterns of a number of these tumour imaging radiopharmaceuticals in normal and pathological tissues has been proposed. Evidence for the validity of this model is presented with specific reference to the ionic state of the reagents concerned. EXperimental evidence to support the proposed model is presented, with reference to the biologic behaviour of the radiopharmaceuticals in normal and pathological tissues. A limited number of selected case reports demonstrate how the results of the earlier described investigations can be applied to explain phenomena observed in clinical studies with ionic substances. The results obtained are discussed and the validity of the data with respect to the proposed model has been investigated. (Auth.)

  2. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

    2015-01-01

    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module......, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules.......The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent modules...

  3. Sex modulates approach systems and impulsivity in substance dependence.

    Science.gov (United States)

    Perry, Robert I; Krmpotich, Theodore; Thompson, Laetitia L; Mikulich-Gilbertson, Susan K; Banich, Marie T; Tanabe, Jody

    2013-11-01

    Personality traits such as pathological engagement in approach behaviors, high levels of impulsivity and heightened negative affect are consistently observed in substance dependent individuals (SDI). The clinical course of addiction has been shown to differ between sexes. For example, women increase their rates of consumption of some drugs of abuse more quickly than men. Despite the potential influence of personality and sex on features of addiction, few studies have investigated the interaction of these factors in substance dependence. Fifty-one SDI (26 males, 25 females) and 66 controls (41 males, 25 females) completed the Behavioral Inhibition/Behavioral Activation System (BIS/BAS) Scales, the Barratt Impulsiveness Scale, and the Positive and Negative Affect Schedule (PANAS-X). Data were analyzed with 2×2 ANCOVAs testing for main effects of group, sex and group by sex interactions, adjusting for education level. Significant group by sex interactions were observed for BAS scores [F(1,116)=7.03, pImpulsiveness [F(1,116)=6.11, pimpulsivity followed by male SDI, male controls, and finally female controls. SDI scored higher on negative affect [F(1,116)=25.23, pwomen than men [F(1,116)=14.03, pimpulsivity in SDI women relative to SDI men and control women suggest that personality traits that have been previously associated with drug use may be modulated by sex. These factors may contribute to differences in the disease course observed in male compared to female drug users. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Specification of the GummyModule Language

    NARCIS (Netherlands)

    Malakuti Khah Olun Abadi, Somayeh

    2012-01-01

    The GummyModule language is an extension to the Java language and is the successor of the EventReactor language The GummyModule language adopts the linguistic constructs of offered by EventReactor to define event types, events and to publish events. As for EventReactor, GummyModule facilitates

  5. Specific Emissions of Harmful Substances from Small Boilers

    Directory of Open Access Journals (Sweden)

    Horák Jiøí

    1998-09-01

    Full Text Available Coal is on of the most important energy source and its significance will increase in a future. In Czech republic coal is except else widely used as a fuel for combustion in a small boilers (up to 50 kW. Low efficiency of the small boilers which is often below 50% together with high emissions of the harmful substances into near surroundings cause in average 40 – 70% of total local air pollution. The research was performed in a scope of the Grant no. 101/98/0820 of Grant Agency of Czech Republic was focused on quality of combustion process related to combustion efficiency and creation of harmful substances at combustion of domestic fuels. Experiments were performed to compare combustion of brown coal, clack coal, coke and black coal slurry. Extremely high creation of harmful substances (CO, NOX, solid particles and organic substances was measured when the black coal slurry was used as a fuel, measured in kg of emissions per GJ of burned fuel. Combustion of brown coal produced significant emissions of solid particles which bond harmful substances as metals, polyaromatic hydrocarbons and others together with high emissions of SO2 . Strong dependence between emissions of CO and low quality of combustion given by low combustion temperature, shortage of combustion air, not suitable design of after-combustion chamber and short duration of fuel presence in a combustion area was found out. Emissions of wide range of metals were investigated. The results of the research grant project describe and explain the combustion process and creation of harmful substances in small boilers plus give suggestions and recommendations leading to rational operation of the small boilers and lowering their negative impact to environment.

  6. Characterization of an organ-specific differentiator substance

    International Nuclear Information System (INIS)

    Steele, V.E.

    1975-01-01

    The objectives of this research are to characterize a diffusible brain inhibitory substance, to elucidate its role in the maintenance of anterior-posterior polarity during head or tail regeneration, and to utilize its action in measuring the differentiative integrity of the stem cells following x-irradiation. Crude, cell-free homogenates of whole planarians (Dugesia etrusca) were centrifuged, Millipore filtered, ultrafiltered using Dow Hollow Fibers, chromatographed using Sephadex and Bio-Gel gel filtration media, electrophoresed using a continuous flow paper electrophoresis apparatus, digested by various enzymatic procedures, and ion focused using LKB Ampholine Electrofocusing equipment. The activities of the various fractions were assayed by placing decapitated planarians in the fractions, then, after nine days the resultant regenerated brain volumes were measured. In order to measure the effect that this substance has on the post-irradiation survival of both the whole animal and the differentiative integrity of the stem cells, x-irradiated planarians were decapitated and allowed to regenerate with or without addition of the inhibitory substance. The inhibitory activity is destroyed when the extract is treated with Pronase, but remains unaffected when treated with RNase, DNase, or Lipase. The inhibitory substance migrates toward the positive electrode when electrophoresed, and has an isoelectric point of between pH 4.75 and 5.38 when isoelectrically focused

  7. Characterization of an organ-specific differentiator substance

    International Nuclear Information System (INIS)

    Steele, V.E.

    1975-01-01

    Cell regeneration in planaria (Dugesia etrusca) was studied. An attempt was made to characterize a diffusible brain inhibitory substance, to elucidate its role in the maintenance of anterior-posterior polarity during head or tail regeneration, and to utilize its action in measuring the differentiative integrity of the stem cells following x-irradiation. (U.S.)

  8. The substance use risk profile scale: a scale measuring traits linked to reinforcement-specific substance use profiles.

    Energy Technology Data Exchange (ETDEWEB)

    Woicik, P.A.; Stewart, S.H.; Pihl, R.O.; Conrod, P.J.

    2009-12-01

    The Substance Use Risk Profile Scale (SURPS) is based on a model of personality risk for substance abuse in which four personality dimensions (hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) are hypothesized to differentially relate to specific patterns of substance use. The current series of studies is a preliminary exploration of the psychometric properties of the SURPS in two populations (undergraduate and high school students). In study 1, an analysis of the internal structure of two versions of the SURPS shows that the abbreviated version best reflects the 4-factor structure. Concurrent, discriminant, and incremental validity of the SURPS is supported by convergent/divergent relationships between the SURPS subscales and other theoretically relevant personality and drug use criterion measures. In Study 2, the factorial structure of the SURPS is confirmed and evidence is provided for its test-retest reliability and validity with respect to measuring personality vulnerability to reinforcement-specific substance use patterns. In Study 3, the SURPS was administered in a more youthful population to test its sensitivity in identifying younger problematic drinkers. The results from the current series of studies demonstrate support for the reliability and construct validity of the SURPS, and suggest that four personality dimensions may be linked to substance-related behavior through different reinforcement processes. This brief assessment tool may have important implications for clinicians and future research.

  9. Local sleep spindle modulations in relation to specific memory cues

    NARCIS (Netherlands)

    Cox, R.; Hofman, W.F.; de Boer, M.; Talamini, L.M.

    2014-01-01

    Sleep spindles have been connected to memory processes in various ways. In addition, spindles appear to be modulated at the local cortical network level. We investigated whether cueing specific memories during sleep leads to localized spindle modulations in humans. During learning of word-location

  10. Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review.

    Science.gov (United States)

    Moura, Carolina Soares; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Amaya-Farfan, Jaime

    2018-05-28

    Interest in the heat shock proteins (HSPs), as a natural physiological toolkit of living organisms, has ranged from their chaperone function in nascent proteins to the remedial role following cell stress. As part of the defence system, HSPs guarantee cell tolerance against a variety of stressors, including exercise, oxidative stress, hyper and hypothermia, hyper and hypoxia and improper diets. For the past couple of decades, research on functional foods has revealed a number of substances likely to trigger cell protection through mechanisms that involve the induction of HSP expression. This review will summarize the occurrence of the most easily inducible HSPs and describe the effects of dietary proteins, peptides, amino acids, probiotics, high-fat diets and other food-derived substances reported to induce HSP response in animals and humans studies. Future research may clarify the mechanisms and explore the usefulness of this natural alternative of defense and the modulating mechanism of each substance.

  11. Design specifications for manufacturability of MCM-C multichip modules

    Energy Technology Data Exchange (ETDEWEB)

    Allen, C.; Blazek, R.; Desch, J.; Elarton, J.; Kautz, D.; Markley, D.; Morgenstern, H.; Stewart, R.; Warner, L.

    1995-06-01

    The scope of this document is to establish design guidelines for electronic circuitry packaged as multichip modules of the ceramic substrate variety, although many of these guidelines are applicable to other types of multichip modules. The guidelines begin with prerequisite information which must be developed between customer and designer of the multichip module. The core of the guidelines focuses on the many considerations that must be addressed during the multichip module design. The guidelines conclude with the resulting deliverables from the design which satisfy customer requirements and/or support the multichip module fabrication and testing processes. Considerable supporting information, checklists, and design constraints are captured in specific appendices and used as reference information in the main body text. Finally some real examples of multichip module design are presented.

  12. Craving and substance use among patients with alcohol, tobacco, cannabis or heroin addiction: a comparison of substance- and person-specific cues.

    Science.gov (United States)

    Fatseas, Melina; Serre, Fuschia; Alexandre, Jean-Marc; Debrabant, Romain; Auriacombe, Marc; Swendsen, Joel

    2015-06-01

    It is well established that craving increases following exposure to substance-related 'cues', but the role of life-styles or substance use habits that are unique to each person remains poorly understood. This study examines the association of substance-specific and personal cues with craving and substance use in daily life. Ecological momentary assessment was used during a 2-week period. Data were collected in a French out-patient addiction treatment centre. A total of 132 out-patients beginning treatment for alcohol, tobacco, cannabis or opiate addiction were included. Using mobile technologies, participants were questioned four times per day relative to craving, substance use and exposure to either substance-specific cues (e.g. seeing a syringe) or personal cues unique to that individual (e.g. seeing the specific person with whom the substance is used). Craving intensity was associated with the number of concurrently assessed substance-specific cues (t = 4.418, P addictive substances, and the duration of this association may persist longer than for more general substance-specific cues. Mobile technologies provide new opportunities for understanding these person-specific risk factors and for providing individually tailored interventions. © 2015 Society for the Study of Addiction.

  13. Genetic modulation of plasma NPY stress response is suppressed in substance abuse: association with clinical outcomes.

    Science.gov (United States)

    Xu, Ke; Hong, Kwangik Adam; Zhou, Zhifeng; Hauger, Richard L; Goldman, David; Sinha, Rajita

    2012-04-01

    Neuropeptide Y (NPY) is involved in stress regulation. Genetic variations predict plasma NPY and neural correlates of emotion and stress. We examined whether the functional NPY haplotype modulates stress-induced NPY and anxiety responses, and if plasma NPY stress responses are associated with substance dependence outcomes. Thirty-seven treatment-engaged, abstinent substance dependent (SD) patients and 28 healthy controls (HCs) characterized on NPY diplotypes (HH: high expression; HLLL: intermediate/low expression) were exposed to stress, alcohol/drug cues and neutral relaxing cues, using individualized guided imagery, in a 3-session laboratory experiment. Plasma NPY, heart rate and anxiety were assessed. Patients were prospectively followed for 90-days post-treatment to assess relapse outcomes. HH individuals showed significantly lower stress-induced NPY with greater heart rate and anxiety ratings, while the HLLL group showed the reverse pattern of NPY, anxiety and heart rate responses. This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype. Lower NPY predicted subsequent higher number of days and greater amounts of post-treatment drug use. These preliminary findings are the first to document chronic drug abuse influences on NPY diplotype expression where NPY diplotype modulation of stress-related plasma NPY, heart rate and anxiety responses was absent in the substance abuse sample. The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Substance Abuse-Specific Knowledge Transfer or Loss? Treatment Program Turnover versus Professional Turnover among Substance Abuse Clinicians

    Science.gov (United States)

    Eby, Lillian T.; Curtis, Sara L.

    2014-01-01

    This longitudinal study investigated the extent to which substance abuse (SA) clinician turnover is associated with SA-specific knowledge loss due to change in professions (professional turnover) versus SA-specific knowledge transfer due to movement from one SA clinical setting to another (treatment program turnover). For this study, clinicians had to voluntarily leave their current treatment program. Eligible clinicians completed a quantitative survey while employed and a qualitative post-employment exit interview 1 year later. Compared to those that exited the SA profession (N = 99), clinicians who changed treatment programs (N = 120) had greater SA-specific formal knowledge and were more likely to be personally in recovery. No differences were found between the two groups in terms of SA-specific practical knowledge. PMID:25115318

  15. Who sells what? Country specific differences in substance availability on the Agora cryptomarket.

    Science.gov (United States)

    Van Buskirk, Joe; Naicker, Sundresan; Roxburgh, Amanda; Bruno, Raimondo; Burns, Lucinda

    2016-09-01

    To date monitoring of cryptomarkets operating on the dark net has largely focused on market size and substance availability. Less is known of country specific differences in these indicators and how they may corroborate population prevalence estimates for substance use in different countries. All substance listings from the cryptomarket Agora were recorded over seven time points throughout February and March 2015. Agora was chosen due to its size as the second largest cryptomarket operating and the level of detail of information provided in individual substance listings. Data were collated and the number of unique sellers selling each substance by country of origin was analysed. An average of 14,456.7 substance listings were identified across sampled days from 868.7 unique sellers. The top five countries by number of listings were the USA, United Kingdom, Australia, China and the Netherlands, collectively accounting for 61.8% of all identified listings and 68% of all unique sellers. Australia was over represented in terms of sellers per capita, while China was over represented in new psychoactive substance (NPS) listings. When examined by number of listings per seller, the Netherlands and China stood out as particularly large, likely due to these countries' role in the local production of various illicit and new psychoactive substances. Numbers of sellers by country of origin appear to be influenced by several factors. Australia's overrepresentation in sellers per capita may indicate its relative geographical isolation and the potential for profit margins from selling online, while China's overrepresentation in NPS listings may reflect domestic production of these substances. Continued monitoring will provide enhanced understanding of the increasingly complex and globalised nature of illicit drug markets. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

    Science.gov (United States)

    Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

    2014-01-01

    NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

  17. Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

    Directory of Open Access Journals (Sweden)

    Nicole L Nichols

    Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

  18. Substance abuse and criminal thinking: testing the countervailing, mediation, and specificity hypotheses.

    Science.gov (United States)

    Walters, Glenn D

    2012-12-01

    The purpose of this study was to determine (a) which of 2 dimensions of criminal thinking (proactive and/or reactive) correlates with prior substance abuse; (b) whether criminal thinking mediates the relationship between prior substance abuse and recidivism; (c) if a direct relationship exists between specific drugs of abuse and specific criminal thinking styles. First, the reconstructed Proactive (Prc) and Reactive (Rrc) Criminal Thinking scores from the Psychological Inventory of Criminal Thinking Styles (PICTS; Walters, 1995) were correlated with a dichotomous measure of prior substance abuse and a continuous measure of the number of substances abused in a sample of 2877 male federal prisoners (age: M = 34.96, SD = 9.89, range = 18-84; race: 63.6% Black, 17.3% White, 17.6% Hispanic, 1.4% other). The results indicated that only the Rrc score correlated significantly with prior substance abuse when the effect of the alternative measure (Prc in the case of Rrc and Rrc in the case of the Prc) was controlled through partial correlations. Second, reactive criminal thinking was found to mediate the relationship between a history of prior substance abuse and subsequent recidivism in a subsample of 1101 inmates who were released from prison during a 1- to 76-month follow-up. Third, both specific (alcohol with cutoff; marijuana with cognitive indolence) and global (heroin, cocaine, and amphetamine with cutoff, cognitive indolence, and discontinuity) drug-criminal thinking correlations were obtained. These results suggest that reactive criminal thinking plays a potentially important role in the drug-crime relationship.

  19. Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes

    Directory of Open Access Journals (Sweden)

    Joseph Schwager

    2016-04-01

    Full Text Available Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL, carnosic acid (CA, carnosic acid-12-methylether (CAME, 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT in murine macrophages (RAW264.7 cells and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO and prostaglandin E2 (PGE2 production in LPS-stimulated macrophages (i.e., acute inflammation. They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6 and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1β (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1β induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis.

  20. Specific determination of clinical and toxicological important substances in biological samples by LC-MS

    International Nuclear Information System (INIS)

    Mitulovic, G.

    2001-02-01

    This thesis of this dissertation is the specific determination of clinical and toxicological important substances in biological samples by LC-MS. Nicotine was determined in serum after application of nicotine plaster and nicotine nasal spray with HPLC-ESI-MS. Cotinine was determined direct in urine with HPLC-ESI-MS. Short time anesthetics were determined in blood and cytostatics were determined in liquor with HPLC-ESI-MS. (botek)

  1. Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers.

    Science.gov (United States)

    Salerno, Simona; Morelli, Sabrina; Giordano, Francesca; Gordano, Amalia; Bartolo, Loredana De

    2016-10-01

    In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

    Science.gov (United States)

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

    Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Quality control of specific patient in radiotherapy with modulated intensity

    International Nuclear Information System (INIS)

    Aberbuj, P D; Tapia Coca, R C

    2012-01-01

    In this work we comment the details of the patient specific quality controls of the first Intensity Modulated Radiotherapy treatment done at Roffo Institute. These controls consisted in two sets of measurements: absolute dose with ionization chamber and relative dose with two dosimetric systems (Gafchromic EBT2 radiochromic films and the PTW 729 ionization chambers array). Two of the filters did not pass the dosimetrical tests, and they were manufactured again. The new filters passed the tests. For the relative two-dimensional measurements the radiochromic films had a better performance than the array due to their higher spatial resolution (author)

  4. Regulating specific organic substances and heavy metals in industrial wastewater discharged to municipal wastewater treatment plants

    DEFF Research Database (Denmark)

    Grüttner, Henrik; Munk, L.; Pedersen, F.

    1994-01-01

    Due to the extension of wastewater treatment plants to nutrient removal and the development towards reuse of sludge m agriculture, new guidelines for regulating industrial discharges m Denmark were needed. The paper describes how a concept for regulating the discharge of specific organic substances...... substances, present knowledge of fate and effects in biological treatment plants is too scarce to underpin the setting of general standards. Therefore, it has been decided to base the developed priority system on the data used in the EEC-system for classification of hazardous chemicals. This includes ready...... degradability, defined by the OECD-test, bio-sorption and bio-accumulation, defined by the octanol/water distribution coefficient and toxic effects on water organisms. Several potential effects of seven heavy metals have been evaluated, and the most critical effects were found to be the quality criteria...

  5. The Association Between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage versus Ischemic Lacunar Infarction

    Directory of Open Access Journals (Sweden)

    Emma H Kaplan

    2014-09-01

    Full Text Available Background: Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH. Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (eg., cocaine, tobacco is associated with subcortical ICH over ischemia in hypertensive individuals.Methods: Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women, >2 drinks per day (men. Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia.Results: Of the 580 patients included in analysis, 217 (37% presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years. Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25% versus 15%, p=0.02, with the largest effect seen in users ≥65 years old (not statistically significant. Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p=0.29.Conclusions: In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH; while use of illicit/controlled substances appears to be predictive of hemorrhage.

  6. Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype.

    Science.gov (United States)

    Leal, Ermelindo C; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E; Kokkotou, Efi; Mooney, David J; LoGerfo, Frank W; Pradhan-Nabzdyk, Leena; Veves, Aristidis

    2015-06-01

    Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Specific fatty acids as metabolic modulators in the dairy cow

    Directory of Open Access Journals (Sweden)

    J.A.A. Pires

    2008-07-01

    Full Text Available This review summarizes recent developments on the utilization of specific fatty acids to modulate bovine energy metabolism, with emphasis on the periparturient dairy cow. A number of experiments have assessed the effects of polyunsaturated fatty acids on bovine hepatic energy metabolism using in vitro and in vivo models. Treatment of hepatocytes with specific fatty acids altered energy metabolism in vitro. For example, linolenic acid seemed to decrease hepatocyte triacylglycerol accumulation. This effect was confirmed in vivo, using parenteral infusions of emulsions derived from different fat sources to feed-restricted non-lactating cows. Additionally, polyunsaturated fatty acids can increase whole body response to insulin, potentially enhancing antilipolytic effects of insulin and muscle protein anabolism in the bovine. There is limited literature on the effects of feeding fat sources rich in omega-3 polyunsaturated fatty acids, such as fish oil and linseed oil, on metabolism of periparturient dairy cows. Available research has yielded conflicting results which need further clarification. On the other hand, specific isomers of conjugated linoleic acid consistently induce milk fat depression and are able to decrease energy export in milk by periparturient dairy cows. Nonetheless, research is still needed to assess whether these effects will ultimately benefit productivity and health status of periparturient dairy cows. Limitations of available methods to protect fatty acids from ruminal biohydrogenation are also addressed.

  8. The Association between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage Versus Ischemic Lacunar Infarction.

    Science.gov (United States)

    Kaplan, Emma H; Gottesman, Rebecca F; Llinas, Rafael H; Marsh, Elisabeth B

    2014-01-01

    Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH). Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (e.g., cocaine, tobacco) is associated with subcortical ICH over ischemia in hypertensive individuals. Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women), >2 drinks per day (men). Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia. Of the 580 patients included in analysis, 217 (37%) presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years). Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25 versus 15%, p = 0.02), with the largest effect seen in users ≥65 years old (not statistically significant). Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p = 0.29). In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH, while use of illicit/controlled substances appears to be predictive of hemorrhage.

  9. Modulation-Frequency-Specific Adaptation in Awake Auditory Cortex

    Science.gov (United States)

    Beitel, Ralph E.; Vollmer, Maike; Heiser, Marc A.; Schreiner, Christoph E.

    2015-01-01

    Amplitude modulations are fundamental features of natural signals, including human speech and nonhuman primate vocalizations. Because natural signals frequently occur in the context of other competing signals, we used a forward-masking paradigm to investigate how the modulation context of a prior signal affects cortical responses to subsequent modulated sounds. Psychophysical “modulation masking,” in which the presentation of a modulated “masker” signal elevates the threshold for detecting the modulation of a subsequent stimulus, has been interpreted as evidence of a central modulation filterbank and modeled accordingly. Whether cortical modulation tuning is compatible with such models remains unknown. By recording responses to pairs of sinusoidally amplitude modulated (SAM) tones in the auditory cortex of awake squirrel monkeys, we show that the prior presentation of the SAM masker elicited persistent and tuned suppression of the firing rate to subsequent SAM signals. Population averages of these effects are compatible with adaptation in broadly tuned modulation channels. In contrast, modulation context had little effect on the synchrony of the cortical representation of the second SAM stimuli and the tuning of such effects did not match that observed for firing rate. Our results suggest that, although the temporal representation of modulated signals is more robust to changes in stimulus context than representations based on average firing rate, this representation is not fully exploited and psychophysical modulation masking more closely mirrors physiological rate suppression and that rate tuning for a given stimulus feature in a given neuron's signal pathway appears sufficient to engender context-sensitive cortical adaptation. PMID:25878263

  10. Toward the Identification of a Specific Psychopathology of Substance Use Disorders

    Directory of Open Access Journals (Sweden)

    Angelo G. I. Maremmani

    2017-04-01

    Full Text Available Addiction is a mental illness in which psychiatric conditions imply a prominent burden. Psychopathological symptoms in substance use disorder (SUD patients are usually viewed as being assignable to the sphere of a personality trait or of comorbidity, leaving doubts about the presence of a specific psychopathology that could only be related to the toxicomanic process. Our research group at the University of Pisa has shed light on the possible definition of a specific psychopathological dimension in SUDs. In heroin use disorder patients, performing an exploratory principal component factor analysis (PCA on all the 90 items included in the SCL-90 questionnaire led to a five-factor solution. The first factor accounted for a depressive “worthlessness and being trapped” dimension; the second factor picked out a “somatic symptoms” dimension; the third identified a “sensitivity–psychoticism” dimension; the fourth a “panic–anxiety” dimension; and the fifth a “violence–suicide” dimension. These same results were replicated by applying the PCA to another Italian sample of 1,195 heroin addicts entering a Therapeutic Community Treatment. Further analyses confirmed the clusters of symptoms, independently of demographic and clinical characteristics, active heroin use, lifetime psychiatric problems, kind of treatment received, and, especially, other substances used by the patient such as alcohol or cocaine. Moreover, these clusters were able to discriminate patients affected by addiction from those affected by psychiatric diseases such as major depressive disorder. Our studies seem to suggest the trait-dependent, rather than the state-dependent, nature of the introduced psychopathology dimensions of SUDs.

  11. Virtual Library Effluent Volume to Soil Disposal Sites Module Specification; TOPICAL

    International Nuclear Information System (INIS)

    M. A. deLamare

    2001-01-01

    This document provides the design specifications for each of the modules identified in the Virtual Library. The design specifications include design logic, input and output specifications, validation, and error handling

  12. Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet.

    Science.gov (United States)

    Van Wagoner, Ryan M; Eichner, Amy; Bhasin, Shalender; Deuster, Patricia A; Eichner, Daniel

    2017-11-28

    Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels. Web-based searches were performed from February 18, 2016, to March 25, 2016, using the Google search engine on the Chrome and Internet Explorer web browsers to identify suppliers selling selective androgen receptor modulators. The products were purchased and the identities of the compounds and their amounts were determined from April to August 2016 using chain-of-custody and World Anti-Doping Association-approved analytical procedures. Analytical findings were compared against the label information. Products marketed and sold as selective androgen receptor modulators. Chemical identities and the amount of ingredients in each product marketed and sold as selective androgen receptor modulators. Among 44 products marketed and sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An additional 17 products (39%) contained another unapproved drug, including the growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated receptor-δ agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44 tested products, no active compound was detected in 4 (9%) and substances not listed on the label were contained in 11 (25%). In only 18 of the 44 products (41%), the amount of active compound in the product matched that listed on the label. The amount of the compounds listed on the label differed substantially from that found by analysis in 26 of 44 products

  13. Sex-specific substance abuse treatment for female healthcare professionals: implications.

    Science.gov (United States)

    Koos, Erin; Brand, Michael; Rojas, Julio; Li, Ji

    2014-01-01

    Gender plays a significant role in the development and treatment of substance abuse disorders. Sex-specific treatment for girls and women has recurrently proven more effective, with better outcomes than traditional treatment. Research on impaired healthcare professionals (HCPs) has largely focused on men, garnering little attention for women and sex differences. With the increasing numbers of female HCPs, it is imperative to identify potential sex differences that may have implications for treatment. Our study compared a convenience sample of male and female HCPs with substance abuse disorders treated in an outpatient program to identify sex differences that may have implications for treatment. Our sample consisted of 96 HCPs (54 men, 42 women) and 17 non-healthcare professional (N-HCP) women. All of the participants were evaluated using the program's clinical interview and the Personality Assessment Inventory (PAI). Chart review data contained categorical variables, qualitative variables, diagnoses, and psychological test scores. A second analysis was conducted through two separate comparisons: the PAI results of comparing impaired female HCPs with impaired male HCPs and the PAI results of comparing impaired female HCPs with impaired female N-HCPs. Statistically significant differences indicated more male participants received prior treatment and more intensive treatment than female participants. More female subjects reported being diagnosed as having a comorbid psychiatric condition and taking psychotropic medications. Several statistically significant differences in the PAI scores were found. Among female HCPs, elevations were found in anxiety, depression, paranoia, and borderline personality disorder. Substantive differences, although not statistically significant, were elevations in somatic complaints and anxiety disorders in female HCPs. In the comparison of female HCPs and N-HCPs, the only statistically significant difference was the significantly higher

  14. The impact of childhood abuse on inpatient substance users: specific links with risky sex, aggression, and emotion dysregulation.

    Science.gov (United States)

    Banducci, Anne N; Hoffman, Elana M; Lejuez, C W; Koenen, Karestan C

    2014-05-01

    Adults with substance use disorders (SUDs) report a high prevalence of childhood abuse. Research in the general population suggests specific types of abuse lead to particular negative outcomes; it is not known whether this pattern holds for adults with SUDs. We hypothesized that specific types of abuse would be associated with particular behavioral and emotional outcomes among substance users. That is, childhood sexual abuse would be associated with risky sex behaviors, childhood physical abuse with aggression, and childhood emotional abuse with emotion dysregulation. 280 inpatients (M age=43.3; 69.7% male; 88.4% African American) in substance use treatment completed the Childhood Trauma Questionnaire (CTQ), HIV Risk-Taking Behavior Scale, Addiction Severity Index, Difficulties with Emotion Regulation Scale (DERS), Distress Tolerance Scale (DTS), and Affect Intensity and Dimensions of Affiliation Motivation (AIM). Consistent with our hypotheses, the CTQ sexual abuse subscale uniquely predicted exchanging sex for cocaine and heroin, number of arrests for prostitution, engaging in unprotected sex with a casual partner during the prior year, and experiencing low sexual arousal when sober. The physical abuse subscale uniquely predicted number of arrests for assault and weapons offenses. The emotional abuse subscale uniquely predicted the DERS total score, AIM score, and DTS score. Among substance users, different types of abuse are uniquely associated with specific negative effects. Assessment of specific abuse types among substance users may be informative in treatment planning and relapse prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

    Directory of Open Access Journals (Sweden)

    Chen Xiaoyu

    2007-12-01

    Full Text Available Abstract Background In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression. Results We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure. Conclusion Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.

  16. Modulation of DNA binding by gene-specific transcription factors.

    Science.gov (United States)

    Schleif, Robert F

    2013-10-01

    The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

  17. Brief report: Bifactor modeling of general vs. specific factors of religiousness differentially predicting substance use risk in adolescence.

    Science.gov (United States)

    Kim-Spoon, Jungmeen; Longo, Gregory S; Holmes, Christopher J

    2015-08-01

    Religiousness is important to adolescents in the U.S., and the significant link between high religiousness and low substance use is well known. There is a debate between multidimensional and unidimensional perspectives of religiousness (Gorsuch, 1984); yet, no empirical study has tested this hierarchical model of religiousness related to adolescent health outcomes. The current study presents the first attempt to test a bifactor model of religiousness related to substance use among adolescents (N = 220, 45% female). Our bifactor model using structural equation modeling suggested the multidimensional nature of religiousness as well as the presence of a superordinate general religiousness factor directly explaining the covariation among the specific factors including organizational and personal religiousness and religious social support. The general religiousness factor was inversely related to substance use. After accounting for the contribution of the general religiousness factor, high organizational religiousness related to low substance use, whereas personal religiousness and religious support were positively related to substance use. The findings present the first evidence that supports hierarchical structures of adolescent religiousness that contribute differentially to adolescent substance use. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  18. 75 FR 79008 - Proposed Collection; Comment Request; Study of Substance Abuse doc.com Module Project

    Science.gov (United States)

    2010-12-17

    ... referral to treatment for patients who abuse substances. The overall goal of this project is to assess the... provide significant services directly to the public to survey customers to determine the kind and quality of services they want and their level of satisfaction with existing services. The project will...

  19. The National Shipbuilding Research Program. Environmental Training Modules. Module 2 Shipyard Craft Specific Training

    Science.gov (United States)

    1999-05-01

    environmental liability. 4) Insecticides and Hazardous Metals Many antifouling coatings contain insecticides such as Tributyltin ( TBT ), and...of potentially toxic substances from shipyard welding operations. ASBESTOS OPERATIONS IN THE SHIPYARD (10ASBTOS.DOC) OBJECTIVE To ensure that...distillation operations. COOLING TOWERS (6-COOLIN.DOC) OBJECTIVE To minimize the potential for toxic emissions from cooling towers. VARNISH DIP TANKS (7

  20. Technical Specification for the CLIC Two-Beam Module

    CERN Document Server

    Riddone, G; Nousiainen, R; Samoshkin, A; Schulte, D; Syratchev, I; Wuensch, W; Zennaro, R

    2008-01-01

    A high-energy (0.5-3 TeV centre-of-mass), highluminosity Compact Linear Collider (CLIC) is being studied at CERN [1]. The CLIC main linacs, 21-km long each, are composed of 2-m long two beam modules. This paper presents their current layout, the main requirements for the different sub-systems (alignment, supporting, stabilization, cooling and vacuum) as well as the status of their integration.

  1. DSM-5 cannabis use disorder, substance use and DSM-5 specific substance-use disorders: Evaluating comorbidity in a population-based sample.

    Science.gov (United States)

    Hayley, Amie C; Stough, Con; Downey, Luke A

    2017-08-01

    Cannabis use disorder (CUD) is frequently associated with concurrent substance use and/or comorbid substance use disorders (SUDs); however there is little specificity with regard to commonly abused individual drug types/classes. This study therefore aimed to provide insight into the degree of these co-occurring relationships across several specific newer and older generation illicit and prescription drugs. 36,309 adults aged 18+ from wave 3 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) were assessed. Weighted cross-tabulations and multivariable logistic regression analyses were used to evaluate comorbidity between current DSM-5 CUD, substance use and DSM-5 SUD. Current DSM-5 CUD is associated with greater lifetime use of all examined drug classes, and previous 12-month use of several newer-class illicit and prescription stimulant-based substances (all pDSM-5 CUD was similarly associated with increased incidence of a range of DSM-5 SUDs and was independently associated with concurrently reporting current DSM-5; sedative (Adjusted OR= 5.1, 95%CI 2.9-9.0), cocaine (AOR= 9.3, 95%CI 5.6-15.5), stimulant (AOR= 4.3, 95%CI 2.3-7.9), club drug (AOR= 16.1, 95%CI 6.3-40.8), opioid (AOR= 4.6, 95%CI 3.0-6.8) and alcohol-use disorder (AOR= 3.0, 95%CI 2.5-3.7); but not heroin or 'other' drug use disorder (both p>0.05). High comorbidity exists between DSM-5 CUD and many specific DSM-5 SUDs. Newer-class illicit and prescription stimulant-based drug use disorders are overrepresented among those with DSM-5 CUD. These findings underscore the need for tailored treatment programs for those presenting with DSM-5 CUD, and for greater treatment specification where poly-drug use is evident. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  2. Substance use disorder and ADHD: is ADHD a particularly "specific" risk factor?

    Science.gov (United States)

    Kousha, Maryam; Shahrivar, Zahra; Alaghband-Rad, Javad

    2012-05-01

    To assess the pattern of substance use disorder (SUD) in adolescents with and without history of attention - deficit / hyperactivity disorder (ADHD) using an Iranian sample in the context of a cultural background and drug availability is differing from Western countries. In this case- control study, the participants were interviewed by a child psychiatrist and the measures included: kiddie Schedule for Affective Disorder and Schizophrenia for school age children (K-SADS), Opium Treatment Index (OTI) and Global Assessment Functioning (GAF). Data were analyzed with chi square test and T test and fisher exact test by EPI.6 soft ware. Adolescents with ADHD were younger at the time of starting cigarette smoking, substance use, abuse and dependency (p = 0.0001), a shorter period between their first-time substance use and substance dependence or abuse (p = 0.0001), more severe substance use (for cannabis, heroine, cigarette and drugs such as benzodiazepines p ADHD group. (p = 0.03) Although the pattern and type of substance use may be different in Iranian culture, our findings about the relationship between ADHD and SUD are similar to other western and non western countries. The presence of ADHD may over-ride cultural barriers and lower availability of drugs to the development of SUD in Iranian adolescents. Early diagnosis and treatment of ADHD may propose with better prognosis of SUD and subsequent decrease in the prevalence of SUD and the costs of SUD-related pathology in this population.

  3. Euglena gracilis Z and its carbohydrate storage substance relieve arthritis symptoms by modulating Th17 immunity.

    Directory of Open Access Journals (Sweden)

    Kengo Suzuki

    Full Text Available Euglena gracilis Z is a microorganism classified as a microalga and is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of E. gracilis Z, is reported to affect the immunological system. This study evaluated the symptom-relieving effects of E. gracilis Z and paramylon in rheumatoid arthritis in a collagen-induced arthritis mouse model. The efficacy of both substances was assessed based on clinical arthritis signs, as well as cytokine (interleukin [IL]-17, IL-6, and interferon [IFN]-γ levels in lymphoid tissues. Additionally, the knee joints were harvested and histopathologically examined. The results showed that both substances reduced the transitional changes in the visual assessment score of arthritis symptoms compared with those in the control group, indicating their symptom-relieving effects on rheumatoid arthritis. Furthermore, E. gracilis Z and paramylon significantly reduced the secretion of the cytokines, IL-17, IL-6, and IFN-γ. The histopathological examination of the control group revealed edema, inflammation, cell hyperplasia, granulation tissue formation, fibrosis, and exudate in the synovial membrane, as well as pannus formation and articular cartilage destruction in the femoral trochlear groove. These changes were suppressed in both treatment groups. Particularly, the E. gracilis Z group showed no edema, inflammation, and fibrosis of the synovial membrane, or pannus formation and destruction of articular cartilage in the femoral trochlear groove. Furthermore, E. gracilis Z and paramylon exhibited symptom-relieving effects on rheumatoid arthritis and suppressed the secretion of cytokines IL-17, IL-6, and IFN-γ. These effects were likely mediated by the regulatory activities of E. gracilis Z and paramylon on Th17 immunity. In addition, the symptom-relieving effects of both substances were comparable, which suggests that paramylon is the active component of Euglena gracilis Z.

  4. Reliability Evaluation of Concentrator Photovoltaic Modules per IEC Qualification Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Tamizhmani, Govindasamy

    2012-12-05

    This project is related to the qualification testing of new generation CPV (concentrator photovoltaics) modules at lower testing costs and lower turnaround time. In this project, the first testing program was completed for two CPV manufacturers, the second testing program was completed for two manufacturers at 65% of the actual testing cost and at less than 3 months of testing turnaround time and the third testing program was completed for two manufacturers at 65% of the actual testing cost and at less than 3 months of testing turnaround time. Due to their financial situation and restructuring, Amonix (one of the CPV manufacturers) intermittently terminated the test programs.

  5. Development of Ethnoscience Approach in The Module Theme Substance Additives to Improve the Cognitive Learning Outcome and Student’s entrepreneurship

    Science.gov (United States)

    Sudarmin; Febu, R.; Nuswowati, M.; Sumarni, W.

    2017-04-01

    Ethnoscience approach is an interesting research today. The purpose of this research is to develop approaches ethnoscience and modules ethnoscience theme additives based ethnoscience; as well as assess the feasibility and effectiveness of module theme additives based ethnoscience to improve learning outcomes and the entrepreneurial character of students. This type of research is the Research and Development (R & D). In this research consist of four stages, namely define, design, development and implementation. The subjects of this study were students of the School of MTs Maarif NU Brebes. Data were analyzed by descriptive qualitative and quantitative. The results showed that ethnoscience approach and the module theme substance additives used declared worthy of National Education Standards Agency (BNSP) with an average percentage of validation on the feasibility aspect of the content, language feasibility, and feasibility of presenting respectively for 94.3%, 86 % and 92% and a very decent entry criteria. The effect of the application modules substance additive based ethnoscience can improve on the cognitive learning classical amounted to 90.63%, and increased learning outcomes category was based on the scores of N-gain. Influence ethnoscience approach application and module theme substances additives based ethnoscience able to improve the entrepreneurial character of students. Based on the results of this study concluded that the ethnoscience approach and module theme substance additives based ethnoscience effective to improve learning outcomes and students’ entrepreneurship.

  6. Symbiont modulates expression of specific gene categories in Angomonas deanei

    Directory of Open Access Journals (Sweden)

    Luciana Loureiro Penha

    Full Text Available Trypanosomatids are parasites that cause disease in humans, animals, and plants. Most are non-pathogenic and some harbor a symbiotic bacterium. Endosymbiosis is part of the evolutionary process of vital cell functions such as respiration and photosynthesis. Angomonas deanei is an example of a symbiont-containing trypanosomatid. In this paper, we sought to investigate how symbionts influence host cells by characterising and comparing the transcriptomes of the symbiont-containing A. deanei (wild type and the symbiont-free aposymbiotic strains. The comparison revealed that the presence of the symbiont modulates several differentially expressed genes. Empirical analysis of differential gene expression showed that 216 of the 7625 modulated genes were significantly changed. Finally, gene set enrichment analysis revealed that the largest categories of genes that downregulated in the absence of the symbiont were those involved in oxidation-reduction process, ATP hydrolysis coupled proton transport and glycolysis. In contrast, among the upregulated gene categories were those involved in proteolysis, microtubule-based movement, and cellular metabolic process. Our results provide valuable information for dissecting the mechanism of endosymbiosis in A. deanei.

  7. Disgust-specific modulation of early attention processes

    NARCIS (Netherlands)

    van Hooff, J.C.; van Buuringen, M.; El M’rabet, L.; de Gier, M.; van Zalingen, L.

    2014-01-01

    Although threatening images are known to attract and keep our attention, little is known about the existence of emotion-specific attention effects. In this study (N. = 46), characteristics of an anticipated, disgust-specific effect were investigated by means of a covert orienting paradigm

  8. Development Modules for Specification of Requirements for a System of Verification of Parallel Algorithms

    Directory of Open Access Journals (Sweden)

    Vasiliy Yu. Meltsov

    2012-05-01

    Full Text Available This paper presents the results of the development of one of the modules of the system verification of parallel algorithms that are used to verify the inference engine. This module is designed to build the specification requirements, the feasibility of which on the algorithm is necessary to prove (test.

  9. Rapid limb-specific modulation of vestibular contributions to ankle muscle activity during locomotion

    NARCIS (Netherlands)

    Forbes, P.A.; Vlutters, M; Dakin, CJ; van der Kooij, H.; Blouin, JS; Schouten, A.C.

    2017-01-01

    During walking, the vestibular influence on locomotor activity is phase-dependent and modulated in both limbs with changes in velocity. It is unclear, however, whether this bilateral modulation is due to a coordinated mechanism between both limbs or instead through limb-specific processes that

  10. Characterization of an organ-specific differentiator substance in the planarian Dugesia etrusca

    Energy Technology Data Exchange (ETDEWEB)

    Steele, V.E.; Lange, C.S.

    1977-01-01

    A substance which inhibits brain formation in decapitated regenerating planarians (Dugesia etrusca) was characterized and partially purified. The substance's inhibitory activity was followed during each purification procedure by adding freshly decapitated animals of a standard size to each fraction, and later measuring the resultant regenerated brain volume. The inhibitory activity remained in the supernatant after a 10000 g centrifugation of a cell-free homogenate. Most of the activity sedimented when the 10000 g supernatant was centrifuged at 32000 g. The degree of inhibitory activity increased with increased numbers of animals in the initial homogenate. The substance has an apparent molecular weight between 2 x 10/sup 5/ and 4 x 10/sup 5/ daltons. Digestion by pronase destroyed the activity, but treatment with RNase, DNase I, or lipase had no significant effect. The inhibiting substance has an isoelectric point (pI) of between 4.75 and 5.38 and migrates to the anode when electrophorezed in pH 6.8 buffer.

  11. Disgust-specific modulation of early attention processes.

    Science.gov (United States)

    van Hooff, Johanna C; van Buuringen, Melanie; El M'rabet, Ihsane; de Gier, Margot; van Zalingen, Lilian

    2014-10-01

    Although threatening images are known to attract and keep our attention, little is known about the existence of emotion-specific attention effects. In this study (N=46), characteristics of an anticipated, disgust-specific effect were investigated by means of a covert orienting paradigm incorporating pictures that were either disgust-evoking, fear-evoking, happiness-evoking or neutral. Attention adhesion to these pictures was measured by the time necessary to identify a peripheral target, presented 100, 200, 500, or 800 ms after picture onset. Main results showed that reaction times were delayed for targets following the disgust-evoking pictures by 100 and 200 ms, suggesting that only these pictures temporarily grabbed hold of participants' attention. These delays were similar for ignore- and attend-instructions, and they were not affected by the participants' anxiety levels or disgust sensitivity. The disgust-specific influence on early attention processes thus appeared very robust, occurring in the majority of participants and without contribution of voluntary- and strategic-attention processes. In contrast, a smaller and less reliable effect of all emotional (arousing) pictures was present in the form of delayed responding in the 100 ms cue-target interval. This effect was more transitory and apparent only in participants with relatively high state-anxiety scores. Practical and theoretical consequences of these findings are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Software requirements specification for the program analysis and control system risk management module

    International Nuclear Information System (INIS)

    SCHAEFER, J.C.

    1999-01-01

    TWR Program Analysis and Control System Risk Module is used to facilitate specific data processes surrounding the Risk Management program of the Tank Waste Retrieval environment. This document contains the Risk Management system requirements of the database system

  13. Unique aspects of impulsive traits in substance use and overeating: specific contributions of common assessments of impulsivity.

    Science.gov (United States)

    Beaton, Derek; Abdi, Hervé; Filbey, Francesca M

    2014-11-01

    Abstract Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Identify unique impulsivity traits specific to substance use and overeating. Impulsive Sensation Seeking (ImpSS) and Barratt's Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n = 37). A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm Overeating: lacks focus, but plans (short and long term). Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories - instead of categories - of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies.

  14. Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments

    Science.gov (United States)

    Gifford, Miriam L.; Banta, Joshua A.; Katari, Manpreet S.; Hulsmans, Jo; Chen, Lisa; Ristova, Daniela; Tranchina, Daniel; Purugganan, Michael D.; Coruzzi, Gloria M.; Birnbaum, Kenneth D.

    2013-01-01

    Plant development is remarkably plastic but how precisely can the plant customize its form to specific environments? When the plant adjusts its development to different environments, related traits can change in a coordinated fashion, such that two traits co-vary across many genotypes. Alternatively, traits can vary independently, such that a change in one trait has little predictive value for the change in a second trait. To characterize such “tunability” in developmental plasticity, we carried out a detailed phenotypic characterization of complex root traits among 96 accessions of the model Arabidopsis thaliana in two nitrogen environments. The results revealed a surprising level of independence in the control of traits to environment – a highly tunable form of plasticity. We mapped genetic architecture of plasticity using genome-wide association studies and further used gene expression analysis to narrow down gene candidates in mapped regions. Mutants in genes implicated by association and expression analysis showed precise defects in the predicted traits in the predicted environment, corroborating the independent control of plasticity traits. The overall results suggest that there is a pool of genetic variability in plants that controls traits in specific environments, with opportunity to tune crop plants to a given environment. PMID:24039603

  15. Substance P reduces apoptotic cell death possibly by modulating the immune response at the early stage after spinal cord injury.

    Science.gov (United States)

    Jiang, Mei Hua; Lim, Ji Eun; Chi, Guang Fan; Ahn, Woosung; Zhang, Mingzi; Chung, Eunkyung; Son, Youngsook

    2013-10-23

    Previously, we have reported that substance P (SP) enhanced functional recovery from spinal cord injury (SCI) possibly by the anti-inflammatory modulation associated with the induction of M2-type macrophages at the injured lesion. In this study, we explored the cytokine expression profiles and apoptotic cell death in the lesion site of the SCI after an immediate intravenous injection of SP. SP injection increased the levels of interleukin-4 (IL-4), IL-6, and IL-10 at day 1 after the SCI approximately by 2-, 9-, and 10-folds when compared with the control SCI, respectively. On the basis of double immunofluorescence staining with IL-10 and CD11b, activated macrophages or microglia expressing IL-10 appeared in the margin of the lesion site at day 1 only after the SP injection. This SP-mediated alteration in the lesion microenvironment was shown to be associated with the lower cell death of neuronal cells at day 1 and oligodendrocytes at day 5 by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which was also accompanied by a decrease in caspase-3 activation. These findings suggest that SP may reduce the inflammation-induced secondary cell death, possibly through immune modulation at an early stage after the SCI.

  16. Culturally Specific Youth Substance Abuse Resistance Skills: Applicability across the U.S.-Mexico Border.

    Science.gov (United States)

    Marsiglia, Flavio F; Kulis, Stephen; Rodriguez, Gregorio Martinez; Becerra, David; Castillo, Jason

    2009-03-01

    This study tests the applicability among adolescents in Mexico of the keepin' it REAL (refuse, explain, avoid, and leave) strategies that are common and effective ways that U.S. youth resist substance use. Following a social learning, communication competence and ecological theory integrated approach, the study draws on self-reported questionnaire data from a non-probability sample of 327 adolescents attending two public high schools in Monterrey, Nuevo León. Multivariate regressions were used to test whether the respondents' use of the REAL strategies by the participants could be predicted by key demographic variables. Separate models were estimated for the frequency of use of each strategy and for different substances. Findings indicate that most adolescents in this sample utilized each of the REAL strategies as well as other strategies to respond to offers of alcohol, cigarettes, or marijuana. Mexican and U.S. youth residing close to the US border appear to use similar drug resistance strategies. Use of the strategies varied considerably by the level of exposure to offers, but only minimally by gender and age. There were no notable differences by socioeconomic status or academic performance. Implications for prevention science, social work practice and social work research are discussed in the context of the bi-national border region and the applicability and prospect for dissemination of U.S. evidence based youth substance use prevention interventions.

  17. Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice.

    Science.gov (United States)

    Xu, J; Xu, F; Barrett, E

    2008-07-01

    Metalloelastase (MMP-12), mainly produced by macrophages, has been shown to play a key role in the pathogenesis of emphysema in animal models. Chronic cigarette smoke increases pulmonary MMP-12, which is closely correlated with an elevation of pulmonary substance P (SP). Because alveolar macrophages (AMs) contain the neurokinin-1 receptor (NK1R), we tested whether SP was able to trigger the upregulation of MMP-12 synthesis in AMs by acting on the NK1R. AMs isolated from bronchoalveolar lavage cells in C3H/HeN mice were cultured with control medium or SP that was coupled without or with NK1R antagonists (CP-99,994 or aprepitant) for 24 h. We found that SP significantly increased the mRNA of MMP-12 and NK1R by 11-fold and 82%, respectively, in AMs (PNCAP) to degenerate PCFs, respectively. Our results show that NCAP treatment significantly decreased mRNA and protein levels of SP associated with a reduction NK1R and MMP-12 in the lungs and AMs. These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs.

  18. Improvement of stability of Nb3 Sn superconductors by introducing high specific heat substances

    Energy Technology Data Exchange (ETDEWEB)

    Xu, X. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Li, P. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Zlobin, A. V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Peng, X. [Unlisted, US, OH

    2018-01-24

    High-Jc Nb3Sn conductors have low stability against perturbations, which accounts for the slow training rates of high-field Nb3Sn magnets. While it is known that adding substances with high specific heat (C) into Nb3Sn wires can increase their overall specific heat and thus improve their stability, there has not been a practical method that is compatible with the fabrication of long-length conductors. In this work, we put forward a scheme to introduce such substances to distributed-barrier Nb3Sn wires, which adds minimum difficulty to the wire manufacturing process. Multifilamentary wires using a mixture of Cu and high-C Gd2O3 powders have been successfully fabricated along this line. Measurements showed that addition of Gd2O3 had no negative effects on residual resitivity ratio or non-Cu Jc, and that flux jumps were remarkably reduced, and minimum quench energy values at 4.2 K, 14 T were increased by a factor of three, indicating that stability was significantly improved. We also discussed the influences of the positioning of high-C substances and their thermal diffusivity on their effectiveness in reducing the superconductor temperature rise against perturbations. Based on these results, we proposed an optimized conductor architecture to maximize the effectiveness of this approach.

  19. Substance-specific importance of EGFR for vascular smooth muscle cells motility in primary culture.

    Science.gov (United States)

    Schreier, Barbara; Schwerdt, Gerald; Heise, Christian; Bethmann, Daniel; Rabe, Sindy; Mildenberger, Sigrid; Gekle, Michael

    2016-07-01

    Besides their importance for the vascular tone, vascular smooth muscle cells (VSMC) also contribute to pathophysiological vessel alterations. Various G-protein coupled receptor ligands involved in vascular dysfunction and remodeling can transactivate the epidermal growth factor receptor (EGFR) of VSMC, yet the importance of EGFR transactivation for the VSMC phenotype is incompletely understood. The aims of this study were (i) to characterize further the importance of the VSMC-EGFR for proliferation, migration and marker gene expression for inflammation, fibrosis and reactive oxygen species (ROS) homeostasis and (ii) to test the hypothesis that vasoactive substances (endothelin-1, phenylephrine, thrombin, vasopressin and ATP) rely differentially on the EGFR with respect to the abovementioned phenotypic alterations. In primary, aortic VSMC from mice without conditional deletion of the EGFR, proliferation, migration, marker gene expression (inflammation, fibrosis and ROS homeostasis) and cell signaling (ERK 1/2, intracellular calcium) were analyzed. VSMC-EGFR loss reduced collective cell migration and single cell migration probability, while no difference between the genotypes in single cell velocity, chemotaxis or marker gene expression could be observed under control conditions. EGF promoted proliferation, collective cell migration, chemokinesis and chemotaxis and leads to a proinflammatory gene expression profile in wildtype but not in knockout VSMC. Comparing the impact of five vasoactive substances (all reported to transactivate EGFR and all leading to an EGFR dependent increase in ERK1/2 phosphorylation), we demonstrate that the importance of EGFR for their action is substance-dependent and most apparent for crowd migration but plays a minor role for gene expression regulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

    Science.gov (United States)

    LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

    2006-03-15

    The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

  1. The impact of oral health conditions, socioeconomic status and use of specific substances on quality of life of addicted persons.

    Science.gov (United States)

    Marques, Tais Cristina Nascimento; Sarracini, Karin Luciana Migliato; Cortellazzi, Karine Laura; Mialhe, Fábio Luiz; de Castro Meneghim, Marcelo; Pereira, Antonio Carlos; Ambrosano, Glaucia Maria Bovi

    2015-03-20

    The aim of this cross-sectional study was to evaluate the impact of oral health conditions, socioeconomic status and use of specific substances on quality of life of alcohol and drug addicted persons, receiving care at outpatient treatment facilities in Brazil. A random sample of 262 participants, mean age 37 years, from Psychosocial Care Centers for Alcohol and Drugs (CAPS AD) located in three cities in the state of São Paulo, Brazil, were clinically examined for caries experience (DMFT index) by a calibrated examiner. They were asked to complete a series of questionnaires, including the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), socioeconomic characteristics, and the World Health Organization Quality of Life assessment (WHOQOL), which were considered the outcome variables of the study. Associations between oral health status, socioeconomic characteristics, substance involvement with WHOQOL were investigated by means of the chi-square test and multiple logistic regression analysis with a level of significance α 14 (OR = 2.25; CI 95% = 1.30-3.89); low-income (OR = 2.41; CI 95% = 1.22-4.77) and users of cocaine/crack (OR = 2.02; CI 95% = 1.15-3.59) were more likely to have poor general quality of life. This study demonstrated that the general quality of life of addicted persons was associated with caries experience, low income and cocaine/crack use.

  2. Study of specific pharmacological activity of standardized composition of bee product substances for treatment of urogenital system

    Directory of Open Access Journals (Sweden)

    V. M. Koval

    2017-10-01

    Full Text Available Introduction. The work presents review of the data literature, which indicate the prospects of creation new highly efficient drugs for the treatment of chronic prostatitis and prostate gland adenoma based bioactive standardized substances of bee products, including powdered honey (PH, propolis phenolic hydrophobic drug (PPHD and bee pollen (BP. Materials and methods. Results of discussion of preclinical pharmacological studies of standardized substances of bee products composition – PH, PPHD and BP for the treatment of specified pathology is given in the experimental part. Results. It was found that the most pronounced anti-inflammatory effect on the level 40 % the mixture of APIs (PH, PPHD and BP detects at a dose of 100 mg/kg in relation to the reference drug – trianom capsules in doses of 100 and 130 mg/kg. Conclusions. Usage of bee products is grounded in creation of the new drug on their basis in the form of standardized substances of bee products composition –PH, PPHD and BP for chronic prostatitis and prostate gland adenoma. It was found that the most pronounced anti-inflammatory effect on 40 % the mixture of APIs (PH, PPHD and BP detects at a dose of 100 mg/kg. It was established that the composition of standard substances of bee products – PH, PPHD and BP at a dose of 100 mg/kg shows a more pronounced specific pharmacological effect in comparison to the reference product – trianom capsules at doses of 100 and 130 mg/kg, which positively affect the course of the pilot prostatitis in male rats caused by dichloroethyl.

  3. Rules specific to nuclear incidence occurring in installations or during transport of nuclear substances

    International Nuclear Information System (INIS)

    Rocamora, P.

    1976-01-01

    International nuclear third party liability conventions deal in depth with the liability system governing the transport of nuclear substances. Without appropriate legislation, international transport would be likely to meet very serious legal difficulties. The rule of nuclear conventions apply the same system to transport as to nuclear installations and mainly enable a determination of the operator liable. They also allow the person responsible for transport to assume liability therefor in place of the operator who whould normally have been liable. These nuclear conventions do not affect application of international transport conventions and this provision has been the cause of serious difficulties regarding maritime transport. This resulted in the adoption in 1971 in Brussels of a convention relating to civil liability in the field of maritime carriage of nuclear material. The purpose of this convention is to establish in the field of maritime transport, the priority of the system of absolute, exclusive and limited liability in the nuclear conventions. (NEA) [fr

  4. Specific activity isolation and determination of radioactive Estrogenic Substances in White Clover

    International Nuclear Information System (INIS)

    Pupiales T, G.; Mejia M, G.

    1986-01-01

    Due to high number of leguminous that exhibit estrogenic activity, subterranean clover between others, which causes infertility in sheep that eat it. It has been considered that white clover (Trifolium repens, variety Ladino, is an specie of low estrogenic activity, however at Bogota City (Colombia) it has high estrogenic activity and may cause reduction in the dairy cattle fertility. Research done in the IAN (today Ingeominas) over this clover variety, showed that the radioactivity substances presents in the white clover have high activity for stradiol, affecting organs from mouse females; Isoflavonoids from vegetables have an anabolism and utero tropic action; estrogenic activity of clover leaves, was exponentially proportional to the amount of ultraviolet radioactivity, falling upon plants during leaves development stage

  5. Organic solar cell modules for specific applications-From energy autonomous systems to large area photovoltaics

    International Nuclear Information System (INIS)

    Niggemann, M.; Zimmermann, B.; Haschke, J.; Glatthaar, M.; Gombert, A.

    2008-01-01

    We report on the development of two types of organic solar cell modules one for energy autonomous systems and one for large area energy harvesting. The first requires a specific tailoring of the solar cell geometry and cell interconnection in order to power an energy autonomous system under its specific operating conditions. We present an organic solar cell module with 22 interconnected solar cells. A power conversion efficiency of 2% under solar illumination has been reached on the active area of 46.2 cm 2 . A voltage of 4 V at the maximum power point has been obtained under indoor illumination conditions. Micro contact printing of a self assembling monolayer was employed for the patterning of the polymer anode. Large area photovoltaic modules have to meet the requirements on efficiency, lifetime and costs simultaneously. To minimize the production costs, a suitable concept for efficient reel-to-reel production of large area modules is needed. A major contribution to reduce the costs is the substitution of the commonly used indium tin oxide electrode by a cheap material. We present the state of the art of the anode wrap through concept as a reel-to-reel suited module concept and show comparative calculations of the module interconnection of the wrap through concept and the standard ITO-based cell architecture. As a result, the calculated overall module efficiency of the anode wrap through module exceeds the overall efficiency of modules based on ITO on glass (sheet resistance 15 Ω/square) and on foils (sheet resistance 60 Ω/square)

  6. Frequency-specific corticofugal modulation of the dorsal cochlear nucleus in mice.

    Science.gov (United States)

    Kong, Lingzhi; Xiong, Colin; Li, Liang; Yan, Jun

    2014-01-01

    The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.

  7. Sensitivity and specificity of a brief personality screening instrument in predicting future substance use, emotional, and behavioral problems: 18-month predictive validity of the Substance Use Risk Profile Scale.

    Science.gov (United States)

    Castellanos-Ryan, Natalie; O'Leary-Barrett, Maeve; Sully, Laura; Conrod, Patricia

    2013-01-01

    This study assessed the validity, sensitivity, and specificity of the Substance Use Risk Profile Scale (SURPS), a measure of personality risk factors for substance use and other behavioral problems in adolescence. The concurrent and predictive validity of the SURPS was tested in a sample of 1,162 adolescents (mean age: 13.7 years) using linear and logistic regressions, while its sensitivity and specificity were examined using the receiver operating characteristics curve analyses. Concurrent and predictive validity tests showed that all 4 brief scales-hopelessness (H), anxiety sensitivity (AS), impulsivity (IMP), and sensation seeking (SS)-were related, in theoretically expected ways, to measures of substance use and other behavioral and emotional problems. Results also showed that when using the 4 SURPS subscales to identify adolescents "at risk," one can identify a high number of those who developed problems (high sensitivity scores ranging from 72 to 91%). And, as predicted, because each scale is related to specific substance and mental health problems, good specificity was obtained when using the individual personality subscales (e.g., most adolescents identified at high risk by the IMP scale developed conduct or drug use problems within the next 18 months [a high specificity score of 70 to 80%]). The SURPS is a valuable tool for identifying adolescents at high risk for substance misuse and other emotional and behavioral problems. Implications of findings for the use of this measure in future research and prevention interventions are discussed. Copyright © 2012 by the Research Society on Alcoholism.

  8. Frequency-specific attentional modulation in human primary auditory cortex and midbrain.

    Science.gov (United States)

    Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

    2018-07-01

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Specific binding of an immunoreactive and biologically active 125I-labeled substance P derivative to mouse mesencephalic cells in primary culture

    International Nuclear Information System (INIS)

    Beaujouan, J.C.; Torrens, Y.; Herbet, A.; Daguet, M.C.; Glowinski, J.; Prochiantz, A.

    1982-01-01

    Binding characteristics of 125 I-labeled Bolton-Hunter substance P ([ 125 I]BHSP), a radioactive analogue of substance P, were studied with mesencephalic primary cultures prepared from embryonic mouse brain. Nonspecific binding represented no more than 20% of the total binding observed on the cells. In contrast, significant specific binding--saturable, reversible, and temperature-dependent--was demonstrated. Scatchard analysis of concentration-dependent binding saturation indicates a single population of noninteracting sites with a high affinity (Kd . 169 pM). Substance P and different substance P analogues were tested for their competitive potencies with regard to [ 125 I]BHSP binding. BHSP itself, substance P, (Tyr8)-substance P, and (nor-Leu11)-substance P strongly inhibited the binding. Good inhibition was also obtained with physalaemin and eledoisin, two peptides structurally related to substance P. When substance P C-terminal fragments were tested for their ability to compete with [ 125 I]BHSP binding, a good relationship was found between competitive activity and peptide length. Regional distribution of [ 125 I]BHSP binding sites was found using primary cultures obtained from different regions of embryonic mouse brain. Mesencephalic, hypothalamic, and striatal cultures had the highest [ 125 I]BHSP binding capacities, whereas cortical, hippocampal, and cerebellar cells shared only little binding activity. Finally, when mesencephalic cells were grown under conditions impairing glial development, [ 125 I]BHSP binding was not affected, demonstrating that binding sites are located on neuronal cells

  10. EORTC radiation proctitis-specific quality of life module - Pretesting in four European countries

    International Nuclear Information System (INIS)

    Halkett, Georgia; Aoun, Samar; Hayne, Dickon; Lund, Jo-Asmund; Gruen, Arne; Villa, Julie; Livi, Lorenzo; Arcangeli, Stefano; Velikova, Galina; Spry, Nigel

    2010-01-01

    Background and purpose: Radiation proctitis is a side effect which can occur after pelvic radiation therapy. Currently available questionnaires do not comprehensively assess the range of problems, nor impact on quality of life associated with proctitis. This article reports on the cultural testing phase of an EORTC module (QLQ-PRT21) developed to assess radiation proctitis specific issues and designed to be used in conjunction with the EORTC core quality of life questionnaire (QLQ-C30). Methods: The previously developed 21-item module, pre-tested in Australia, was translated into Norwegian, German, French and Italian. Patients completed the EORTC QLQ-C30 and module questionnaires towards the end of their radical pelvic radiation treatment to target acute side effects. Patients experiencing chronic proctitis were also surveyed. Patients also participated in structured interviews to determine issues of comprehensibility, coverage and relevance. Results were compared with Australian data. Results: Questionnaires were completed by 64 European patients. The module was found to be relevant and culturally acceptable to participants. Feedback has led to minor translation modifications and the inclusion of two additional questions. Conclusion: This module is ready for Phase IV testing which will consist of large scale field testing with the aim to perform psychometric analysis and finalise a module that will be suitable in the assessment of radiation induced proctitis.

  11. Niger Republic Mineral Planning : Part IV - first volume : Main mineral substances specific study and their geological context

    International Nuclear Information System (INIS)

    Franconi, Antoine; Joo', Julien; Zibo, Idde

    1981-01-01

    This volume contains the detailed study of mineral substances industrially exploited to date : uranium, coal, non metallic building materials and public activities, and non conventionally exploited substances, that are : tin, columbite-tantalite, tungsten, gold, phosphates and evaporates [fr

  12. 41 CFR 102-75.130 - If hazardous substance activity took place on the property, what specific information must an...

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If hazardous substance... Utilization of Excess Real Property Title Report § 102-75.130 If hazardous substance activity took place on... quantity of such hazardous substance and the time at which such storage, release, or disposal took place...

  13. Dynamics of growth/mature-related substances in vegetables using specific triple labeled compound

    International Nuclear Information System (INIS)

    Yamato, Yoichi; Hamano, Megumi; Yamazaki, Hiroko; Miura, Hiroyuki

    2000-01-01

    To progress physiological studies of vegetables, development of biosynthetic method for production of triple labeled compounds was attempted in this study and such method for vegetables using specifically labeled sugars was examined. As a sugar compound, 6-C 14 -glucose (14-CG) and 1-H 3 -glucose (3-HG) were given to culture medium for cells derived from tomato embryonic axis and the changes of these compounds were monitored. Tomato embryonic cells were harvested 20 and 44 hours after the addition of 14-CG or 3-CG into the culture medium the cells. The cells were homogenized and the supernatant after centrifugation was applied onto HPLC. Radio analyzer revealed major two peaks in the chromatography of the sugar fraction from the cells after 20 hours from the addition of 14-CG. One was the peak of glucose, itself and the other was estimated to be that of fructose based on the retention time. Whereas in the elution pattern of the sugar fraction after 44 hours from the addition, a peak of sucrose was found along with the peak of glucose. These results indicate that C 14 in 14-CG but not H 3 in 3-HG was transferred into fructose after the metabolism in tomato. Moreover, in both elution patterns, there was a peak positioned at the same retention time, indicating that the compound in this peak was produced from either of 14-CG or 3-HG. Therefore, it is thought that H 3 and C 14 double-labeled compound could be produced from the cell culture added with both labeled compounds; 14-CG and 3-HG. (M.N.)

  14. Antibody-mediated modulation of cytokinins in tobacco: Organ-specific changes in cytokinin homeostasis

    Czech Academy of Sciences Publication Activity Database

    Gelová, Z.; Hoopen, P.; Novák, Ondřej; Motyka, Václav; Pernisová, M.; Dabravolski, S.; Didi, V.; Tillack, F.; Oklešťková, Jana; Strnad, Miroslav; Hause, B.; Haruštiaková, D.; Conrad, U.; Janda, L.; Hejátko, J.

    2018-01-01

    Roč. 69, č. 3 (2018), s. 441-454 ISSN 0022-0957 R&D Projects: GA MŠk(CZ) LQ1601; GA MŠk(CZ) LO1204; GA MŠk(CZ) LM2015062; GA ČR(CZ) GA16-14649S Institutional support: RVO:61389030 Keywords : Antibody-mediated modulation * biosynthesis * ckx * cytokinin * homeostasis * organ specificity * tobacco Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 5.830, year: 2016

  15. Nrf2 pathway modulates Substance P-induced human mast cell activation and degranulation in the hair follicle.

    Science.gov (United States)

    Jadkauskaite, Laura; Bahri, Rajia; Farjo, Nilofer; Farjo, Bessam; Jenkins, Gail; Bhogal, Ranjit; Haslam, Iain; Bulfone-Paus, Silvia; Paus, Ralf

    2018-05-30

    Activation of Nrf2 in primary human mast cells exposed to oxidative stress induced by substance P suppresses pro-inflammatory gene transcription, activation and degranulation. Copyright © 2018. Published by Elsevier Inc.

  16. Specificity of the Human Frequency Following Response for Carrier and Modulation Frequency Assessed Using Adaptation.

    Science.gov (United States)

    Gockel, Hedwig E; Krugliak, Alexandra; Plack, Christopher J; Carlyon, Robert P

    2015-12-01

    The frequency following response (FFR) is a scalp-recorded measure of phase-locked brainstem activity to stimulus-related periodicities. Three experiments investigated the specificity of the FFR for carrier and modulation frequency using adaptation. FFR waveforms evoked by alternating-polarity stimuli were averaged for each polarity and added, to enhance envelope, or subtracted, to enhance temporal fine structure information. The first experiment investigated peristimulus adaptation of the FFR for pure and complex tones as a function of stimulus frequency and fundamental frequency (F0). It showed more adaptation of the FFR in response to sounds with higher frequencies or F0s than to sounds with lower frequency or F0s. The second experiment investigated tuning to modulation rate in the FFR. The FFR to a complex tone with a modulation rate of 213 Hz was not reduced more by an adaptor that had the same modulation rate than by an adaptor with a different modulation rate (90 or 504 Hz), thus providing no evidence that the FFR originates mainly from neurons that respond selectively to the modulation rate of the stimulus. The third experiment investigated tuning to audio frequency in the FFR using pure tones. An adaptor that had the same frequency as the target (213 or 504 Hz) did not generally reduce the FFR to the target more than an adaptor that differed in frequency (by 1.24 octaves). Thus, there was no evidence that the FFR originated mainly from neurons tuned to the frequency of the target. Instead, the results are consistent with the suggestion that the FFR for low-frequency pure tones at medium to high levels mainly originates from neurons tuned to higher frequencies. Implications for the use and interpretation of the FFR are discussed.

  17. Niger Republic mineral planning : Part four Second volume : Main mineral substances specific study and their geological context

    International Nuclear Information System (INIS)

    Franconi, Antoine; Joo', Julien; Zibo, Idde

    1981-01-01

    This volume describes Niger Republic mineral substances capable of rising economic interest. After relating minerals occurrence , indices and deposits types, conclusions and recommendations have been made for mineral prospecting. Mineral substances described are : Copper, lead and zinc, molybdena, iron, manganese, titanium, vanadium, nickel and chrome ( cobalt and platinoid ), lithium, lignite, diamond and diverse substances rare earth, beryllium, silver, bismuth arsenic and antimony, barytine, alunite, talc and asbestos ( graphite and diatomite) [fr

  18. Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Christopher W Pohlmeyer

    Full Text Available Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.

  19. Research and development of system to utilize photovoltaic energy. Survey on the specific purpose modules; Taiyoko hatsuden riyo system no kenkyu kaihatsu. Taiyoto module ni kansuru chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Tatsuta, M [New Energy and Industrial Technology Development Organization, Tokyo (Japan)

    1994-12-01

    This paper reports the survey results on the specific purpose modules for photovoltaic power generation in fiscal 1994. (1) On the feasibility survey on new application fields, it was clarified that photovoltaic power generation is applicable to extensive areas such as farmland, road, railway and public facility as latent demand sites. (2) On the optimum modules for various specific purposes, the structure, production method, cost estimation and issues of various modules were studied for desert, wasteland, coast, ocean, river, embankment, railway, road, mobile facility and arcade. (3) On the survey on new materials and material development, various conventional materials and materials promising for required performance were surveyed for every application. (4) On the survey on technology trends, the survey members participated in the first international photovoltaic energy conversion conference and the photovoltaic power generation workshop, while the members held the 1st-5th specific purpose module subcommittees. 1 tab.

  20. Activated human nasal epithelial cells modulate specific antibody response against bacterial or viral antigens.

    Directory of Open Access Journals (Sweden)

    Chiou-Yueh Yeh

    Full Text Available Nasal mucosa is an immune responsive organ evidenced by eliciting both specific local secretory IgA and systemic IgG antibody responses with intra-nasal administration of antigens. Nevertheless, the role of nasal epithelial cells in modulating such responses is unclear. Human nasal epithelial cells (hNECs obtained from sinus mucosa of patients with chronic rhinosinusitis were cultured in vitro and firstly were stimulated by Lactococcus lactis bacterium-like particles (BLPs in order to examine their role on antibody production. Secondly, both antigens of immunodominant protein IDG60 from oral Streptococcus mutans and hemagglutinin (HA from influenza virus were tested to evaluate the specific antibody response. Stimulated hNECs by BLPs exhibited a significant increase in the production of interleukin-6 (IL-6, and thymic stromal lymphopoietin (TSLP. Conditioned medium of stimulated hNECs has effects on enhancing the proliferation of CD4+ T cells together with interferon-γ and IL-5 production, increasing the costimulatory molecules on dendritic cells and augmenting the production of IDG60 specific IgA, HA specific IgG, IgA by human peripheral blood lymphocytes. Such production of antigen specific IgG and IgA is significantly counteracted in the presence of IL-6 and TSLP neutralizing antibodies. In conclusion, properly stimulated hNECs may impart immuno-modulatory effects on the antigen-specific antibody response at least through the production of IL-6 and TSLP.

  1. Brief Report: Bifactor Modeling of General vs. Specific Factors of Religiousness Differentially Predicting Substance Use Risk in Adolescence

    OpenAIRE

    Kim-Spoon, Jungmeen; Longo, Gregory S.; Holmes, Christopher J.

    2015-01-01

    Religiousness is important to adolescents in the U.S., and the significant link between high religiousness and low substance use is well known. There is a debate between multidimensional and unidimensional perspectives of religiousness (Gorsuch, 1984); yet, no empirical study has tested this hierarchical model of religiousness related to adolescent health outcomes. The current study presents the first attempt to test a bifactor model of religiousness related to substance use among adolescents...

  2. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons

    Science.gov (United States)

    Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel

    2014-01-01

    SUMMARY Human imaging studies have revealed that intranasal administration of the “prosocial” hormone oxytocin (OT) activates the frontal cortex, and that this action of OT correlates with enhanced brain function in autism. Here we report the discovery of a population of somatostatin (Sst) positive, regular spiking interneurons that express the oxytocin receptor (OxtrINs). Silencing of OxtrINs in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice specifically during the sexually receptive phase of the estrous cycle. This sociosexual deficit was also present in mice in which the Oxtr gene was conditionally deleted from the mPFC, and in control mice infused with an Oxtr antagonist. Our data demonstrate a gender, cell type and state specific role for OT/Oxtr signaling in the mPFC, and identify a latent cortical circuit element that may modulate other complex social behaviors in response to OT. PMID:25303526

  3. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.

    Directory of Open Access Journals (Sweden)

    Martin H Schaefer

    2014-06-01

    Full Text Available Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors and the output (transcription factors layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.

  4. A validated specific stability-indicating RP-HPLC assay method for Ambrisentan and its related substances.

    Science.gov (United States)

    Narayana, M B V; Chandrasekhar, K B; Rao, B M

    2014-09-01

    A validated specific stability-indicating reverse-phase liquid chromatographic method was developed for the quantitative determination of Ambrisentan as well as its related substances in bulk samples, pharmaceutical dosage forms in the presence of degradation products and its related impurities. Forced degradation studies were performed on bulk samples of Ambrisentan as per the ICH-prescribed stress conditions using acid, base, oxidative, thermal stress and photolytic degradation to show the stability-indicating power of the LC method. Significant degradation in acidic, basic stress conditions was observed and no degradation was observed in other stress conditions. The chromatographic method was optimized using the samples generated from the forced degradation studies and the impurity-spiked solution. Good resolution between the peaks corresponds to Ambrisentan-related impurities and degradation products from the analyte were achieved on a SunFire C18 column using a mobile phase consisting of a mixture of potassium dihydrogen orthophosphate at a pH adjusted to 2.5 with ortho-phosphoric acid in water and a mixture of acetonitrile:methanol using a simple linear gradient. The detection was carried out at 225 nm. The limit of detection and the limit of quantification for the Ambrisentan and its related impurities were established. The stressed test solutions were assayed against the qualified working standard of Ambrisentan and the mass balance in each case was between 98.9 and 100.3%, indicating that the developed LC method was stability indicating. Validation of the developed LC method was carried out as per the ICH requirements. The developed method was found to be suitable to check the quality of bulk samples of Ambrisentan at the time of batch release and also during its storage (long-term and accelerated stability). © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. THE OPPORTUNITIES AND SPECIFICS OF THE POLYMERS APPLICATION AS AUXILIARY SUBSTANCE IN THE COSMETICS COMPOSITIONS BASED ON NATURAL MINERAL SALTS

    Directory of Open Access Journals (Sweden)

    B. B. Sysuev

    2017-01-01

    Full Text Available These days Natural mineral salts (biologically active ingredients, which are the components of thermal springs, sea water, brine lakes, minerals (bischofite are widely used in the composition of cosmetic products. The ability to influence the formulations stability and the sensory properties of cosmetics products is the specificity of this materials group, which creates certain difficulties in the development of a composition. The polymers’ use as gelling agents and thickeners is one of the means of formulations stability improving.The aim was scientific and technical literature review of the polymers assortment used in cosmetics with natural mineral salts, their application in the cosmetic compositions and the influence of mineral salts on the properties of polymers solutions.Materials and methods. Resources such as eLIBRARY, PubMed, Cyberleninca, as well as the websites of the manufacturers and suppliers of auxiliary materials, and finished cosmetic products were used to obtain the data.Results and discussion. Analysis of literature data and technical information suggests that cellulose derivatives, xanthan gum, and polyvinylpyrrolidone and carbomer are the most commonly used polymers in cosmetic compositions with natural mineral salts. These substances carry out functions of gelling agents, stabilizers, emulsifiers, binders, sensorial modifier agents. There is insufficient information about the interaction of polymers with the natural mineral salts and their influence on polymers properties in scientific and technical literature. The complexity and uniqueness of the composition of natural salts also represents certain difficulty in the evaluation of the interaction.Conclusion. Thus, regularities and peculiarities of natural mineral salts influence on the stability of solutions of polymers used in cosmetics as thickeners and gelling agents, is a promising direction of modern pharmaceutical practices study. 

  6. Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor

    International Nuclear Information System (INIS)

    Tahri-Joutei, A.; Pointis, G.

    1988-01-01

    Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. ( 3 H)-AVP was found to bind to a single class of sites with high affinity and low capacity. Binding displacements with specific selection analogs of AVP indicated the presence of V 1 subtype receptors on Leydig cells. The ability of AVP to displace ( 3 H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace ( 3 H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells. This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation. AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation. This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels

  7. Alkylglycerols modulate the proliferation and differentiation of non-specific agonist and specific antigen-stimulated splenic lymphocytes.

    Directory of Open Access Journals (Sweden)

    Linxi Qian

    Full Text Available Alkylglycerols (AKGs are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed that oral AKGs administration significantly increased the immune response in mice. The aim of the present study was to investigate the in vitro immunomodulatory effect of AKGs on stimulating splenic lymphocyte responses. C57BL/6 mice were immunized with hepatitis B surface antigen (HBsAg. Splenic B cells were purified and stimulated with anti-BCR and anti-CD38. Meanwhile, splenic CD4+ T cells were purified and stimulated with anti-CD3 and anti-CD28. For antigen specific stimulation, the purified CD4+ T cells were cocultured with HBsAg -pulsed dendritic cells. The stimulated lymphocytes were treated with different concentrations of AKGs. The cell proliferation was assessed by [3H]-thymidine incorporation assay. The maturation of B cells was assessed by examining the germline (GL transcription of IgG (γ1 mRNA expression, and the surface expressions of CD80/CD86 markers were examined by flow cytometry analysis. Th1/Th2 polarity was assessed by T-BET (Th1/GATA-3 (Th2 flow cytometry assay and by characteristic cytokines ELISA assay (TNF-α and IFN-γ for Th1; IL-4 and IL-10 for Th2. It was found that AKGs significantly increased the BCR/CD38 -stimulated B cell proliferation. The T cell proliferation in response to CD3/CD28 or specific antigen stimulation was also increased by AKGs. The transcriptional level of IgG (γ1 and the expressions of CD80/CD86 molecules were markedly increased by AKGs in BCR/CD38 -stimulated B cells. Meanwhile, the results showed that AKGs increased the expression of T-BET transcriptional factor and the production of Th1 cytokines (TNF-α and IFN-γ upon CD3/CD28 stimulation; whereas, levels of Th2 cytokines (IL-4 and IL-10 were decreased by AKGs. Our study demonstrated that AKGs can modulate immune responses by boosting the proliferation and maturation of murine lymphocytes in vitro.

  8. Atomic force microscopy study on specificity and non-specificity of interaction forces between Enterococcus faecalis cells with and without aggregation substance

    NARCIS (Netherlands)

    Waar, Karola; van der Mei, Henderina; Harmsen, Hermie JM; de Vries, Jacob; Atema-Smit, Jelly; Degener, John E; Busscher, Hendrik

    Enterococcus faecalis is one of the leading causes of hospital-acquired infections, and indwelling medical devices are especially prone to infection. E faecalis expressing aggregation substance (Agg) adheres to biomaterial surfaces by means of positive cooperativity, i.e. the ability of one adhering

  9. Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

    Directory of Open Access Journals (Sweden)

    María Cecilia Albareda

    2015-05-01

    Full Text Available The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th1 and interleukin (IL-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

  10. Gender-specific associations between involvement in team sport culture and canadian adolescents’ substance-use behavior

    Directory of Open Access Journals (Sweden)

    Randy Boyes

    2017-12-01

    While team sport participation confers only a small increased risk for substance use, the prevalence of sport participation results in a large population impact. Given this fact, interventions such as education for parents and coaches and policies encouraging engagement in a variety of extracurricular activities should be explored.

  11. Species-specific chitin-binding module 18 expansion in the amphibian pathogen Batrachochytrium dendrobatidis.

    Science.gov (United States)

    Abramyan, John; Stajich, Jason E

    2012-01-01

    Batrachochytrium dendrobatidis is the causative agent of chytridiomycosis, which is considered one of the driving forces behind the worldwide decline in populations of amphibians. As a member of the phylum Chytridiomycota, B. dendrobatidis has diverged significantly to emerge as the only pathogen of adult vertebrates. Such shifts in lifestyle are generally accompanied by various degrees of genomic modifications, yet neither its mode of pathogenicity nor any factors associated with it have ever been identified. Presented here is the identification and characterization of a unique expansion of the carbohydrate-binding module family 18 (CBM18), specific to B. dendrobatidis. CBM (chitin-binding module) expansions have been likened to the evolution of pathogenicity in a variety of fungus species, making this expanded group a prime candidate for the identification of potential pathogenicity factors. Furthermore, the CBM18 expansions are confined to three categories of genes, each having been previously implicated in host-pathogen interactions. These correlations highlight this specific domain expansion as a potential key player in the mode of pathogenicity in this unique fungus. The expansion of CBM18 in B. dendrobatidis is exceptional in its size and diversity compared to other pathogenic species of fungi, making this genomic feature unique in an evolutionary context as well as in pathogenicity. Amphibian populations are declining worldwide at an unprecedented rate. Although various factors are thought to contribute to this phenomenon, chytridiomycosis has been identified as one of the leading causes. This deadly fungal disease is cause by Batrachochytrium dendrobatidis, a chytrid fungus species unique in its pathogenicity and, furthermore, its specificity to amphibians. Despite more than two decades of research, the biology of this fungus species and its deadly interaction with amphibians had been notoriously difficult to unravel. Due to the alarming rate of worldwide

  12. Preservatives and neutralizing substances in milk: analytical sensitivity of official specific and nonspecific tests, microbial inhibition effect, and residue persistence in milk

    Directory of Open Access Journals (Sweden)

    Livia Cavaletti Corrêa da Silva

    2015-09-01

    Full Text Available Milk fraud has been a recurring problem in Brazil; thus, it is important to know the effect of most frequently used preservatives and neutralizing substances as well as the detection capability of official tests. The objective of this study was to evaluate the analytical sensitivity of legislation-described tests and nonspecific microbial inhibition tests, and to investigate the effect of such substances on microbial growth inhibition and the persistence of detectable residues after 24/48h of refrigeration. Batches of raw milk, free from any contaminant, were divided into aliquots and mixed with different concentrations of formaldehyde, hydrogen peroxide, sodium hypochlorite, chlorine, chlorinated alkaline detergent, or sodium hydroxide. The analytical sensitivity of the official tests was 0.005%, 0.003%, and 0.013% for formaldehyde, hydrogen peroxide, and hypochlorite, respectively. Chlorine and chlorinated alkaline detergent were not detected by regulatory tests. In the tests for neutralizing substances, sodium hydroxide could not be detected when acidity was accurately neutralized. The yogurt culture test gave results similar to those obtained by official tests for the detection of specific substances. Concentrations of 0.05% of formaldehyde, 0.003% of hydrogen peroxide and 0.013% of sodium hypochlorite significantly reduced (P

  13. The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex.

    Science.gov (United States)

    Chavez, Candice M; McGaugh, James L; Weinberger, Norman M

    2009-05-01

    Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1-28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cortex (A1) to the frequency of a conditioned stimulus (CS), and the greater the level of CS importance, the larger the area of representational gain [Weinberger, N. M. (2007). Associative representational plasticity in the auditory cortex: A synthesis of two disciplines. Learning & Memory, 14(1-2), 1-16]. The two lines of research suggest that BLA strengthening of memory might be accomplished in part by increasing the representation of an environmental stimulus. The present study investigated whether stimulation of the BLA can affect cortical memory representations. In male Sprague-Dawley rats studied under urethane general anesthesia, frequency receptive fields were obtained from A1 before and up to 75min after the pairing of a tone with BLA stimulation (BLAstm: 100 trials, 400ms, 100Hz, 400microA [+/-16.54]). Tone started before and continued after BLAstm. Group BLA/1.0 (n=16) had a 1s CS-BLAstm interval while Group BLA/1.6 (n=5) has a 1.6s interval. The BLA/1.0 group did develop specific tuning shifts toward and to the CS, which could change frequency tuning by as much as two octaves. Moreover, its shifts increased over time and were enduring, lasting 75min. However, group BLA/1.6 did not develop tuning shifts, indicating that precise CS-BLAstm timing is important in the anesthetized animal. Further, training in the BLA/1.0 paradigm but stimulating outside of the BLA did not produce tuning shifts. These findings demonstrate that the BLA is capable of exerting highly specific

  14. Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules.

    Science.gov (United States)

    Zhu, Jinwei; Shang, Yuan; Xia, Caihao; Wang, Wenning; Wen, Wenyu; Zhang, Mingjie

    2011-11-25

    Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tissue developments, cell-cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. Here we show that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner. The structure of the DLG1 SH3-GK tandem in complex with a phospho-LGN peptide reveals that the GMP-binding site of GK has evolved into a specific pSer/pThr-binding pocket. Residues both N- and C-terminal to the pSer are also critical for the specific binding of the phospho-LGN peptide to GK. We further demonstrate that the previously reported GK domain-mediated interactions of DLGs with other targets, such as GKAP/DLGAP1/SAPAP1 and SPAR, are also phosphorylation dependent. Finally, we provide evidence that other MAGUK GKs also function as phospho-peptide-binding modules. The discovery of the phosphorylation-dependent MAGUK GK/target interactions indicates that MAGUK scaffold-mediated signalling complex organizations are dynamically regulated.

  15. Auditory-visual integration modulates location-specific repetition suppression of auditory responses.

    Science.gov (United States)

    Shrem, Talia; Murray, Micah M; Deouell, Leon Y

    2017-11-01

    Space is a dimension shared by different modalities, but at what stage spatial encoding is affected by multisensory processes is unclear. Early studies observed attenuation of N1/P2 auditory evoked responses following repetition of sounds from the same location. Here, we asked whether this effect is modulated by audiovisual interactions. In two experiments, using a repetition-suppression paradigm, we presented pairs of tones in free field, where the test stimulus was a tone presented at a fixed lateral location. Experiment 1 established a neural index of auditory spatial sensitivity, by comparing the degree of attenuation of the response to test stimuli when they were preceded by an adapter sound at the same location versus 30° or 60° away. We found that the degree of attenuation at the P2 latency was inversely related to the spatial distance between the test stimulus and the adapter stimulus. In Experiment 2, the adapter stimulus was a tone presented from the same location or a more medial location than the test stimulus. The adapter stimulus was accompanied by a simultaneous flash displayed orthogonally from one of the two locations. Sound-flash incongruence reduced accuracy in a same-different location discrimination task (i.e., the ventriloquism effect) and reduced the location-specific repetition-suppression at the P2 latency. Importantly, this multisensory effect included topographic modulations, indicative of changes in the relative contribution of underlying sources across conditions. Our findings suggest that the auditory response at the P2 latency is affected by spatially selective brain activity, which is affected crossmodally by visual information. © 2017 Society for Psychophysiological Research.

  16. Gender-specific associations between involvement in team sport culture and canadian adolescents' substance-use behavior.

    Science.gov (United States)

    Boyes, Randy; O'Sullivan, Dylan E; Linden, Brooke; McIsaac, Michael; Pickett, William

    2017-12-01

    Canadian adolescents have some of the highest rates of substance use in the world. The etiology of this phenomenon has not been fully explored, and one possible contextual determinant is involvement in sport activities that foster risk-taking behaviors through physical and social mechanisms. Using the 2013-14 Health Behaviour in School Aged Children (HBSC) study we therefore examined this hypothesis in a contemporary national sample of Canadian adolescents. The strength and direction of the relationship between sport and substance use varied by gender and substance, with team sport participation associated with increased binge drinking (RR 1.33 [95% CI 1.13-1.56] for boys, RR 1.21 [1.06-1.38] for girls) and use of smokeless tobacco (RR 1.68 [1.34-2.10] for boys, RR 1.32 [1.01-1.72] for girls), but with lower prevalence levels of cannabis use (RR 0.73 [95% CI 0.61-0.88]) and cigarette smoking (RR 0.79 [95% CI 0.70-0.89]) in girls alone. We also compared team sport athletes with high social involvement (sports team as primary peer group) and physical involvement (higher number of days/week physically active) to those with low involvement. For boys, the combination of high physical and high social involvement was associated with the highest risk, while high social involvement alone was associated with the greatest risk for girls. While team sport participation confers only a small increased risk for substance use, the prevalence of sport participation results in a large population impact. Given this fact, interventions such as education for parents and coaches and policies encouraging engagement in a variety of extracurricular activities should be explored.

  17. D-Zero detector electronics Run IIb upgrade project: VME LVDS SERDES buff (VLSB) module specification

    Energy Technology Data Exchange (ETDEWEB)

    Rapisarda, Stefano M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Rubinov, Paul M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Wilcer, Neal G. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2011-03-09

    The D0 VME64 LVDS SERDES Buffer (D0 VLSB) is a VME64 [Ref. ] single wide 6U module used for testing the Analog Front-End boards system [Ref. ]. The module is a custom LVDS SERDES Buffer with 4 LVDS inputs channels and can be operated stand-alone with minimal additional hardware. The current testing needs require only a 4 channel D0 VLSB module but the design allows system expansion to multiple modules. A D0 VLSB module can receive/generate trigger signals over two Lemo© [Ref. ] connectors on the module front panel. A normal test system configuration consist of a VME 64 subrack were slot 1 is occupied by a VME subrack controller and the D0 VLSB cards will occupy one or more of the remaining slots.

  18. Electro-acupuncture at different acupoints modulating the relative specific brain functional network

    Science.gov (United States)

    Fang, Jiliang; Wang, Xiaoling; Wang, Yin; Liu, Hesheng; Hong, Yang; Liu, Jun; Zhou, Kehua; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing

    2010-11-01

    Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

  19. Standard Specification for Steel Blades Used with the Photovoltaic Module Surface Cut Test

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2009-01-01

    1.1 This specification specifies the recommended physical characteristics of the steel blades required for the surface cut test described in ANSI/UL 1703 (Section 24) and IEC 61730-2 (Paragraph 10.3). 1.2 ANSI/UL 1703 and IEC 61730-2 are standards for photovoltaic module safety testing. 1.3 This standard provides additional fabrication details for the surface cut test blades that are not provided in ANSI/UL 1703 or IEC 61730-2. Surface cut test blades that have out-of-tolerance corner radii or burrs are known to cause erroneous test results, either passes or failures. 1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.5 This standard does not purport to address all of the safety problems, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

  20. Rapid limb-specific modulation of vestibular contributions to ankle muscle activity during locomotion

    NARCIS (Netherlands)

    Forbes, Patrick A.; Vlutters, Mark; Dakin, Christopher J.; van der Kooij, Herman; Blouin, Jean Sébastien; Schouten, Alfred C.

    2017-01-01

    Key points: -The vestibular influence on human walking is phase-dependent and modulated across both limbs with changes in locomotor velocity and cadence. -Using a split-belt treadmill, we show that vestibular influence on locomotor activity is modulated independently in each limb. -The independent

  1. Intensity modulated radiation therapy: Analysis of patient specific quality control results, experience of Rene-Gauducheau Centre

    International Nuclear Information System (INIS)

    Chiavassa, S.; Brunet, G.; Gaudaire, S.; Munos-Llagostera, C.; Delpon, G.; Lisbona, A.

    2011-01-01

    Purpose. - Systematic verifications of patient's specific intensity-modulated radiation treatments are usually performed with absolute and relative measurements. The results constitute a database which allows the identification of potential systematic errors. Material and methods. - We analyzed 1270 beams distributed in 232 treatment plans. Step-and-shoot intensity-modulated radiation treatments were performed with a Clinac (6 and 23 MV) and sliding window intensity-modulated radiation treatments with a Novalis (6 MV). Results. - The distributions obtained do not show systematic error and all the control meet specified tolerances. Conclusion. - These results allow us to reduce controls specific patients for treatments performed under identical conditions (location, optimization and segmentation parameters of treatment planning system, etc.). (authors)

  2. A retrospective analysis for patient-specific quality assurance of volumetric-modulated arc therapy plans

    International Nuclear Information System (INIS)

    Li, Guangjun; Wu, Kui; Peng, Guang; Zhang, Yingjie; Bai, Sen

    2014-01-01

    Volumetric-modulated arc therapy (VMAT) is now widely used clinically, as it is capable of delivering a highly conformal dose distribution in a short time interval. We retrospectively analyzed patient-specific quality assurance (QA) of VMAT and examined the relationships between the planning parameters and the QA results. A total of 118 clinical VMAT cases underwent pretreatment QA. All plans had 3-dimensional diode array measurements, and 69 also had ion chamber measurements. Dose distribution and isocenter point dose were evaluated by comparing the measurements and the treatment planning system (TPS) calculations. In addition, the relationship between QA results and several planning parameters, such as dose level, control points (CPs), monitor units (MUs), average field width, and average leaf travel, were also analyzed. For delivered dose distribution, a gamma analysis passing rate greater than 90% was obtained for all plans and greater than 95% for 100 of 118 plans with the 3%/3-mm criteria. The difference (mean ± standard deviation) between the point doses measured by the ion chamber and those calculated by TPS was 0.9% ± 2.0% for all plans. For all cancer sites, nasopharyngeal carcinoma and gastric cancer have the lowest and highest average passing rates, respectively. From multivariate linear regression analysis, the dose level (p = 0.001) and the average leaf travel (p < 0.001) showed negative correlations with the passing rate, and the average field width (p = 0.003) showed a positive correlation with the passing rate, all indicating a correlation between the passing rate and the plan complexity. No statistically significant correlation was found between MU or CP and the passing rate. Analysis of the results of dosimetric pretreatment measurements as a function of VMAT plan parameters can provide important information to guide the plan parameter setting and optimization in TPS

  3. A retrospective analysis for patient-specific quality assurance of volumetric-modulated arc therapy plans

    Energy Technology Data Exchange (ETDEWEB)

    Li, Guangjun [Radiation Physics Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan (China); Wu, Kui [Department of Radiotherapy, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province (China); Peng, Guang; Zhang, Yingjie [Radiation Physics Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan (China); Bai, Sen, E-mail: baisen@scu.edu.cn [Radiation Physics Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan (China)

    2014-01-01

    Volumetric-modulated arc therapy (VMAT) is now widely used clinically, as it is capable of delivering a highly conformal dose distribution in a short time interval. We retrospectively analyzed patient-specific quality assurance (QA) of VMAT and examined the relationships between the planning parameters and the QA results. A total of 118 clinical VMAT cases underwent pretreatment QA. All plans had 3-dimensional diode array measurements, and 69 also had ion chamber measurements. Dose distribution and isocenter point dose were evaluated by comparing the measurements and the treatment planning system (TPS) calculations. In addition, the relationship between QA results and several planning parameters, such as dose level, control points (CPs), monitor units (MUs), average field width, and average leaf travel, were also analyzed. For delivered dose distribution, a gamma analysis passing rate greater than 90% was obtained for all plans and greater than 95% for 100 of 118 plans with the 3%/3-mm criteria. The difference (mean ± standard deviation) between the point doses measured by the ion chamber and those calculated by TPS was 0.9% ± 2.0% for all plans. For all cancer sites, nasopharyngeal carcinoma and gastric cancer have the lowest and highest average passing rates, respectively. From multivariate linear regression analysis, the dose level (p = 0.001) and the average leaf travel (p < 0.001) showed negative correlations with the passing rate, and the average field width (p = 0.003) showed a positive correlation with the passing rate, all indicating a correlation between the passing rate and the plan complexity. No statistically significant correlation was found between MU or CP and the passing rate. Analysis of the results of dosimetric pretreatment measurements as a function of VMAT plan parameters can provide important information to guide the plan parameter setting and optimization in TPS.

  4. A retrospective analysis for patient-specific quality assurance of volumetric-modulated arc therapy plans.

    Science.gov (United States)

    Li, Guangjun; Wu, Kui; Peng, Guang; Zhang, Yingjie; Bai, Sen

    2014-01-01

    Volumetric-modulated arc therapy (VMAT) is now widely used clinically, as it is capable of delivering a highly conformal dose distribution in a short time interval. We retrospectively analyzed patient-specific quality assurance (QA) of VMAT and examined the relationships between the planning parameters and the QA results. A total of 118 clinical VMAT cases underwent pretreatment QA. All plans had 3-dimensional diode array measurements, and 69 also had ion chamber measurements. Dose distribution and isocenter point dose were evaluated by comparing the measurements and the treatment planning system (TPS) calculations. In addition, the relationship between QA results and several planning parameters, such as dose level, control points (CPs), monitor units (MUs), average field width, and average leaf travel, were also analyzed. For delivered dose distribution, a gamma analysis passing rate greater than 90% was obtained for all plans and greater than 95% for 100 of 118 plans with the 3%/3-mm criteria. The difference (mean ± standard deviation) between the point doses measured by the ion chamber and those calculated by TPS was 0.9% ± 2.0% for all plans. For all cancer sites, nasopharyngeal carcinoma and gastric cancer have the lowest and highest average passing rates, respectively. From multivariate linear regression analysis, the dose level (p = 0.001) and the average leaf travel (p < 0.001) showed negative correlations with the passing rate, and the average field width (p = 0.003) showed a positive correlation with the passing rate, all indicating a correlation between the passing rate and the plan complexity. No statistically significant correlation was found between MU or CP and the passing rate. Analysis of the results of dosimetric pretreatment measurements as a function of VMAT plan parameters can provide important information to guide the plan parameter setting and optimization in TPS. Copyright © 2014 American Association of Medical Dosimetrists. Published by

  5. The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex

    OpenAIRE

    Chavez, Candice M.; McGaugh, James L.; Weinberger, Norman M.

    2008-01-01

    Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cor...

  6. Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

    Science.gov (United States)

    Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

    2016-01-01

    Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

  7. Application of the modulated temperature differential scanning calorimetry technique for the determination of the specific heat of copper nanofluids

    International Nuclear Information System (INIS)

    De Robertis, E.; Cosme, E.H.H.; Neves, R.S.; Kuznetsov, A.Yu.; Campos, A.P.C.; Landi, S.M.; Achete, C.A.

    2012-01-01

    The purpose of this work is to investigate the applicability of the modulated temperature differential scanning calorimetry technique to measure specific heat of copper nanofluids by using the ASTM E2719 standard procedure, which is generally applied to thermally stable solids and liquids. The one-step method of preparation of copper nanofluid samples is described. The synthesized nanoparticles were separated from the base fluid and examined by X-ray diffraction and transmission electron microscopy in order to evaluate their structure, morphology and chemical nature. The presence of copper nanoparticles in the base fluid alters the characteristics of crystallization and melting processes and reduces the specific heat values of nanofluids in the whole studied temperature range. - Highlights: ► Copper nanofluids prepared by one-step method. ► Methodology of synthesis improved nanofluid stability. ► Specific heat determinations using modulated temperature differential scanning calorimetry. ► Good agreement between theoretical and experimental values.

  8. English for Specific Purposes (ESP Modules in the Self-Access Learning Center (SALC for Success in the Global Workplace

    Directory of Open Access Journals (Sweden)

    Kevin Knight

    2010-09-01

    Full Text Available University students must prepare themselves to be successful members of the global workforce, and this paper introduces one way for a self-access center to support such preparation by students outside of the formal classroom environment. In this paper, it is proposed that the Self-Access Learning Center (SALC at Kanda University of International Studies (KUIS provide ESP (English for specific purposes modules intended to prepare students for their future careers. Within these self-study modules, the following should be recognized and incorporated: 1. The principles of ESP 2. Elements of outcome-based education 3. The relationship between leadership, learning, and teachingIn describing such ESP modules, this paper also proposes the development of self-access materials that could be made available to facilitate the independent study.

  9. Species-specific profiles and risk assessment of perfluoroalkyl substances in coral reef fishes from the South China Sea.

    Science.gov (United States)

    Pan, Chang-Gui; Yu, Ke-Fu; Wang, Ying-Hui; Zhang, Rui-Jie; Huang, Xue-Yong; Wei, Chao-Shuai; Wang, Wei-Quan; Zeng, Wei-Bin; Qin, Zhen-Jun

    2018-01-01

    The contamination profiles of sixteen perfluoroalkyl substances (PFAS) were examined in coral reef fish samples collected from the South China Sea (SCS) where no information about this topic was available in the literature. The results revealed that six PFAS were found in coral reef fish samples from the SCS. Perfluorooctane sulfonate (PFOS) was the most predominant PFAS contaminant detected in most of the samples, with the highest concentration value of 27.05 ng/g wet weight (ww) observed in Cephalopholis urodelus. Perfluoroundecanoic acid (PFUnDA) and Perfluorotridecanoic acid (PFTrDA) were the second and third dominant PFAS, respectively. Mean PFOS concentrations in muscle of seven coral reef fish varied from 0.29 ng/g ww in Lethrinus olivaceus to 10.78 ng/g ww in Cephalopholis urodelus. No significant linear relationship was observed between PFOS levels and coral reef fish traits (length, weight) collected in this region. Average daily intake of PFOS for the seven coral reef fishes ranged from 0.79 ng/kg/d for Lethrinus olivaceus to 29.53 ng/kg/d for Cephalopholis urodelus. The hazard ratio (HR) values for human consumption of PFOS-contaminated coral reef fishes ranged from 0.04 to 1.48, with Cephalopholis urodelus having the highest HR value of 1.18 (higher than 1) among the species, indicating frequent consumption of Cephalopholis urodelus might pose potential health risk to local population. The present work have provided the first hand data of PFAS in coral reef fishes in the SCS and indirectly demonstrated the existence of low level PFAS pollution in the SCS in China. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Horticultural therapy: a pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans.

    Science.gov (United States)

    Detweiler, Mark B; Self, Jennifer A; Lane, Sandra; Spencer, Luise; Lutgens, Brian; Kim, Dong-Yun; Halling, Mary H; Rudder, Tammie C; Lehmann, Lauren P

    2015-01-01

    Horticultural therapy (HT) is a subgroup of occupational therapy (OT). Both HT and OT have been successful as adjunctive treatment modalities in substance abuse treatment. Studies have indicated that gardening promotes neuroendocrine and affective restoration from stress. The study intended to assess the effect of HT versus nonhorticultural OT on cortisol levels, depression, symptoms of posttraumatic stress disorder (PTSD), alcohol cravings, and quality of life. The research team designed a randomized pilot study. The study was open for participation from July 2012-October 2012. It took place during multiple occurrences of a 28-d treatment programs for substance use disorder at a Veterans Affairs medical center. Participants • Participants were 49 veterans, averaging 46.4 y old (SD = 11.9); the dropout rate was 37%. Participants were randomly assigned to the HT or the OT group. They attended supervised HT and OT groups 5 h/d for 3 wk. Outcome Measures • Pre- and posttreatment, participants completed the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), the Alcohol Craving Questionnaire (ACQ-NOW), the Posttraumatic Stress Disorder Checklist Civilian Version (PCLC), and the Center for Epidemiologic Studies Depression Scale (CES-D). Salivary cortisol samples were taken at wk 1, 2, and 3. A repeated measures analysis of variance (ANOVA) (F2,20 = 0.878) revealed that the HT performed was associated with a 12% reduction in salivary cortisol levels from wk 1 to wk 3, but the difference was not statistically significant (P = .43). Separate 1-way analyses of covariance (ANCOVAs) revealed no statistically significant differences in the self-administered tests, although both the Q-LES-Q-SF and CES-D showed a trend toward improving quality of life and depressive symptoms in the HT group compared with the OT group. Additional analysis of the nonbiologic tests suggests that most participants in the HT and OT had some benefit from the

  11. The impact of pediatric-specific dose modulation curves on radiation dose and image quality in head computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Joana; Paulo, Graciano [Instituto Politecnico de Coimbra, ESTESC, DMIR, Coimbra (Portugal); Foley, Shane; Rainford, Louise [University College Dublin, School of Medicine and Medical Science, Health Science Centre, Dublin 4 (Ireland); McEntee, Mark F. [The University of Sydney, Faculty of Health Sciences, Cumberland Campus, Sydney (Australia)

    2015-11-15

    The volume of CT examinations has increased with resultant increases in collective dose values over the last decade. To analyze the impact of the tube current and voltage modulation for dose values and image quality of pediatric head CT examinations. Head CT examinations were performed on anthropomorphic phantoms and four pediatric age categories before and after the introduction of dedicated pediatric curves for tube voltage and current modulation. Local diagnostic reference levels were calculated. Visual grading characteristic image quality evaluation was performed by four pediatric neuroradiologists and image noise comparisons were performed. Pediatric-specific modulation curves demonstrated a 49% decrease in mean radiation dose for phantom examinations. The local diagnostic reference levels (CTDIvol) for clinical examinations decreased by 52%, 41%, 46% and 40% for newborn, 5-, 10- and 15-year-old patients, respectively. Visual grading characteristic image quality was maintained for the majority of age categorizations (area under the curve = 0.5) and image noise measurements did not change (P = 0.693). Pediatric-specific dose modulation curves resulted in an overall mean dose reduction of 45% with no significant differences in subjective or objective image quality findings. (orig.)

  12. The impact of pediatric-specific dose modulation curves on radiation dose and image quality in head computed tomography

    International Nuclear Information System (INIS)

    Santos, Joana; Paulo, Graciano; Foley, Shane; Rainford, Louise; McEntee, Mark F.

    2015-01-01

    The volume of CT examinations has increased with resultant increases in collective dose values over the last decade. To analyze the impact of the tube current and voltage modulation for dose values and image quality of pediatric head CT examinations. Head CT examinations were performed on anthropomorphic phantoms and four pediatric age categories before and after the introduction of dedicated pediatric curves for tube voltage and current modulation. Local diagnostic reference levels were calculated. Visual grading characteristic image quality evaluation was performed by four pediatric neuroradiologists and image noise comparisons were performed. Pediatric-specific modulation curves demonstrated a 49% decrease in mean radiation dose for phantom examinations. The local diagnostic reference levels (CTDIvol) for clinical examinations decreased by 52%, 41%, 46% and 40% for newborn, 5-, 10- and 15-year-old patients, respectively. Visual grading characteristic image quality was maintained for the majority of age categorizations (area under the curve = 0.5) and image noise measurements did not change (P = 0.693). Pediatric-specific dose modulation curves resulted in an overall mean dose reduction of 45% with no significant differences in subjective or objective image quality findings. (orig.)

  13. Category Specific Knowledge Modulate Capacity Limitations of Visual Short-Term Memory

    DEFF Research Database (Denmark)

    Dall, Jonas Olsen; Watanabe, Katsumi; Sørensen, Thomas Alrik

    2016-01-01

    We explore whether expertise can modulate the capacity of visual short-term memory, as some seem to argue that training affects capacity of short-term memory [13] while others are not able to find this modulation [12]. We extend on a previous study [3] demonstrating expertise effects by investiga...... are in line with the theoretical interpretation that visual short-term memory reflects the sum of the reverberating feedback loops to representations in long-term memory.......We explore whether expertise can modulate the capacity of visual short-term memory, as some seem to argue that training affects capacity of short-term memory [13] while others are not able to find this modulation [12]. We extend on a previous study [3] demonstrating expertise effects......), and expert observers (Japanese university students). For both the picture and the letter condition we find no performance difference in memory capacity, however, in the critical hiragana condition we demonstrate a systematic difference relating expertise differences between the groups. These results...

  14. Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules

    OpenAIRE

    Zhu, Jinwei; Shang, Yuan; Xia, Caihao; Wang, Wenning; Wen, Wenyu; Zhang, Mingjie

    2011-01-01

    Membrane-associated guanylate kinases (MAGUK) family proteins contain an inactive guanylate kinase (GK) domain, whose function has been elusive. Here, this domain is revealed as a new type of phospho-peptide-binding module, in which the GMP-binding site has evolved to accommodate phospho-serines or -threonines.

  15. Niger Republic Mineral Planning : Part IV - first volume : Main mineral substances specific study and their geological context; Plan Mineral de la Republique du Niger : Tome IV - 1er volume : Etude specifique des principales substances minerals et leur contexte geologique

    Energy Technology Data Exchange (ETDEWEB)

    Franconi, Antoine; Joo' , Julien; Zibo, Idde

    1981-07-01

    This volume contains the detailed study of mineral substances industrially exploited to date : uranium, coal, non metallic building materials and public activities, and non conventionally exploited substances, that are : tin, columbite-tantalite, tungsten, gold, phosphates and evaporates. [French] Ce volume contient l'etude detaillee des substances minerals exploitees industriellement a ce jour : l'uranium, le charbon, les materiaux non metalliques de construction et de travaux publics et les substances exploitees artisanalement qui sont : l'etain, la Colombo-tantalite, le tungstene, l'or, les phosphates et les evaporates.

  16. Attack in a subway by an explosive containing radioactive substance. Specificities of the taking charge and assistance organization

    International Nuclear Information System (INIS)

    Curet, P.M.

    1999-01-01

    The use of explosives with radioactive material in them during an attack in the subway obliges several specificities in the help organisation, in the taking charge of victims and in the environmental management for the broadest meaning. That is the purpose of this article. (N.C.)

  17. Waste Receiving and Processing Facility Module 1 Data Management System software requirements specification

    International Nuclear Information System (INIS)

    Rosnick, C.K.

    1996-01-01

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-0126). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  18. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    International Nuclear Information System (INIS)

    Brann, E.C. II.

    1994-01-01

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  19. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    Brann, E.C. II

    1994-09-09

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal.

  20. Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

    Science.gov (United States)

    Pripfl, Jürgen; Lamm, Claus

    2015-02-01

    Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  1. Validation of the PedsQL Epilepsy Module: A pediatric epilepsy-specific health-related quality of life measure.

    Science.gov (United States)

    Modi, Avani C; Junger, Katherine F; Mara, Constance A; Kellermann, Tanja; Barrett, Lauren; Wagner, Janelle; Mucci, Grace A; Bailey, Laurie; Almane, Dace; Guilfoyle, Shanna M; Urso, Lauryn; Hater, Brooke; Hustzi, Heather; Smith, Gigi; Herrmann, Bruce; Perry, M Scott; Zupanc, Mary; Varni, James W

    2017-11-01

    To validate a brief and reliable epilepsy-specific, health-related quality of life (HRQOL) measure in children with various seizure types, treatments, and demographic characteristics. This national validation study was conducted across five epilepsy centers in the United States. Youth 5-18 years and caregivers of youth 2-18 years diagnosed with epilepsy completed the PedsQL Epilepsy Module and additional questionnaires to establish reliability and validity of the epilepsy-specific HRQOL instrument. Demographic and medical data were collected through chart reviews. Factor analysis was conducted, and internal consistency (Cronbach's alphas), test-retest reliability, and construct validity were assessed. Questionnaires were analyzed from 430 children with epilepsy (M age = 9.9 years; range 2-18 years; 46% female; 62% white: non-Hispanic; 76% monotherapy, 54% active seizures) and their caregivers. The final PedsQL Epilepsy Module is a 29-item measure with five subscales (i.e., Impact, Cognitive, Sleep, Executive Functioning, and Mood/Behavior) with parallel child and caregiver reports. Internal consistency coefficients ranged from 0.70-0.94. Construct validity and convergence was demonstrated in several ways, including strong relationships with seizure outcomes, antiepileptic drug (AED) side effects, and well-established measures of executive, cognitive, and emotional/behavioral functioning. The PedsQL Epilepsy Module is a reliable measure of HRQOL with strong evidence of its validity across the epilepsy spectrum in both clinical and research settings. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  2. Specification and development of the sharing memory data management module for a nuclear processes simulator

    International Nuclear Information System (INIS)

    Telesforo R, D.

    2003-01-01

    Actually it is developed in the Engineering Faculty of UNAM a simulator of nuclear processes with research and teaching purposes. It consists of diverse modules, included the one that is described in the present work that is the shared memory module. It uses the IPC mechanisms of the UNIX System V operative system, and it was codified with C language. To model the diverse components of the simulator the RELAP code is used. The function of the module is to generate locations of shared memory for to deposit in these the necessary variables for the interaction among the diverse ones processes of the simulator. In its it will be able read and to write the information that generate the running of the simulation program, besides being able to interact with the internal variables of the code in execution time. The graphic unfolding (mimic, pictorials, tendency graphics, virtual instrumentation, etc.) they also obtain information of the shared memory. In turn, actions of the user in interactive unfolding, they modify the segments of shared memory, and the information is sent to the RELAP code to modify the simulation course. The program has two beginning modes: automatic and manual. In automatic mode taking an enter file of RELAP (indta) and it joins in shared memory, the control variables that in this appear. In manual mode the user joins, he reads and he writes the wanted control variables, whenever they exist in the enter file (indta). This is a dynamic mode of interacting with the simulator in a direct way and of even altering the values as when its don't exist in the board elements associated to the variables. (Author)

  3. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

    Science.gov (United States)

    Bredewold, Remco; Smith, Caroline J. W.; Dumais, Kelly M.; Veenema, Alexa H.

    2014-01-01

    We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me2)AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior. PMID:24982623

  4. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

    Directory of Open Access Journals (Sweden)

    Remco eBredewold

    2014-06-01

    Full Text Available We recently demonstrated that vasopressin (AVP in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage as opposed to familiar (home cage social environments. Administration of the specific AVP V1a receptor (V1aR antagonist (CH25Tyr(Me2AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH25-[Tyr(Me2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze, but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

  5. Task-specific modulation of human auditory evoked responses in a delayed-match-to-sample task

    Directory of Open Access Journals (Sweden)

    Feng eRong

    2011-05-01

    Full Text Available In this study, we focus our investigation on task-specific cognitive modulation of early cortical auditory processing in human cerebral cortex. During the experiments, we acquired whole-head magnetoencephalography (MEG data while participants were performing an auditory delayed-match-to-sample (DMS task and associated control tasks. Using a spatial filtering beamformer technique to simultaneously estimate multiple source activities inside the human brain, we observed a significant DMS-specific suppression of the auditory evoked response to the second stimulus in a sound pair, with the center of the effect being located in the vicinity of the left auditory cortex. For the right auditory cortex, a non-invariant suppression effect was observed in both DMS and control tasks. Furthermore, analysis of coherence revealed a beta band (12 ~ 20 Hz DMS-specific enhanced functional interaction between the sources in left auditory cortex and those in left inferior frontal gyrus, which has been shown to involve in short-term memory processing during the delay period of DMS task. Our findings support the view that early evoked cortical responses to incoming acoustic stimuli can be modulated by task-specific cognitive functions by means of frontal-temporal functional interactions.

  6. Iodide- and bromide-specific electron-capture/photodetachment-modulated detector for the trace analysis of halocarbon mixtures

    International Nuclear Information System (INIS)

    Mock, R.S.; Grimsrud, E.P.

    1988-01-01

    The use of photodetachment (PD) of electrons from negative ions in a pulsed electron capture detector (ECD) is described. By passing a chopped light beam through the ECD and amplification of the modulated component of the ECD signal, the photodetachment-modulated (PDM) pulsed ECD can be made to respond selectively and sensitively to iodine- containing hydrocarbons alone, or to iodine- and bromine-containing hydrocarbons in the presence of chlorinated hydrocarbons. The detection limit of the iodide/bromide-specific mode of the PDM-ECD to CH 3 I is shown to be competitive with that of the normal mode of the pulsed ECD. This detection mode of the ECD is shown to be of great assistance in the gas chromatographic analysis of organobromides and organoiodides in complex mixtures which contain a large number of organochlorides

  7. Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg

    2016-01-01

    mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT...... injections, or SLIT tablets or neither. PBMC were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG peptide pools. Phenotypic characterization of cytokine producing cells was performed by FACS. RESULTS: In the SCIT group, decreased IL-5 production...

  8. Reliability and validity of the Norwegian child and parent versions of the DISABKIDS Chronic Generic Module (DCGM-37 and Diabetes-Specific Module (DSM-10

    Directory of Open Access Journals (Sweden)

    Frøisland Dag

    2012-02-01

    Full Text Available Abstract Background International guidelines on type 1 diabetes advocate routine screening of health-related quality of life (HRQOL. DISABKIDS questionnaires are the first instruments developed across cultures and nations to provide age-appropriate measures of HRQOL in children with chronic diseases. DISABKIDS includes a Chronic Generic Module 37 (DCGM-37 and disease-specific modules. The purpose of this study was to examine reliability and validity of the Norwegian versions of the DISABKIDS questionnaires in children and adolescents with type 1 diabetes. Methods The DCGM-37 and the Diabetes Specific Module-10 (DDM-10 were translated into Norwegian using standard forward-backward translation. Eight to 19 year old children and adolescents with type 1 diabetes scheduled for routine follow-up at three diabetic clinics in Norway and one of their parents were invited to complete the DCGM-37 and the DDM-10. Internal consistency was determined using Cronbach's alpha. Results were compared with those of the Child Health Questionnaire Children Form-87 (CHQ-CF87 and Child Health Questionnaire Parent Form-50 which are established generic questionnaires. DISABKIDS results were related to age, gender, duration of diabetes, mode of insulin delivery and metabolic control. Clinical data were obtained from the Norwegian Childhood Diabetes Registry. Results Of 198 eligible child-parent dyads, 103 (52% completed the questionnaires. Mean age was 13.6 (2.6, range 8-19 yrs, 52% were boys. Cronbach's alpha was > 0.70 for all the DISABKIDS sub-scales except two (physical ability and social inclusion. There were moderate to high correlations (0.65-0.81 between the DISABKIDS scales and mental/emotional sub-scales of CHQ-CF87. Increasing age and higher HbA1c were significantly associated with reduced HRQOL scores. Parents tended to score their child's HRQOL lower than the children/adolescents themselves. Conclusions The study shows that the DISABKIDS instruments are

  9. GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

    Science.gov (United States)

    Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

    2015-07-29

    The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

  10. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    Science.gov (United States)

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  11. Niger Republic mineral planning : Part four Second volume : Main mineral substances specific study and their geological context; Plan mineral de la Republique du Niger : Tome IV : 2e Volume : Etude specifique des principales substances minerales et leur contexte geologique

    Energy Technology Data Exchange (ETDEWEB)

    Franconi, Antoine; Joo' , Julien; Zibo, Idde

    1981-07-01

    This volume describes Niger Republic mineral substances capable of rising economic interest. After relating minerals occurrence , indices and deposits types, conclusions and recommendations have been made for mineral prospecting. Mineral substances described are : Copper, lead and zinc, molybdena, iron, manganese, titanium, vanadium, nickel and chrome ( cobalt and platinoid ), lithium, lignite, diamond and diverse substances rare earth, beryllium, silver, bismuth arsenic and antimony, barytine, alunite, talc and asbestos ( graphite and diatomite) [French] Ce volume decrit les substances susceptibles de presenter un interet economique au Niger. Apres avoir relate leurs occurrences , indices et types de gisement auxquels elles appartiennent des conclusions et recommendations ont ete faites pour la prospection. Les substances ainsi decrites sont : le cuivre, le plomb et le zinc, le molybdene, le fer, le manganese, le titane et le vanadium, le nickel et le chrome (Cobalt et platinoides), le lithium, le lignite, le diamant et les substances diverses ( terres rares, beryllium), argent, bismuth, arsenic et antimoine, barytine, alunite, talc et amiante (graphite et diatomite)

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

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

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

  13. SPECIFICS OF ELABORATING METHODOLOGY TO TEACH INNOVATIVE COMPETENCE USING EMBEDDABLE MODULE

    Directory of Open Access Journals (Sweden)

    Nikolai I. Naumkin

    2016-12-01

    Full Text Available Introduction: the article is concerned with the development of competence when teaching students innovative activity. The analysis of bachelor’s degree programmes in engineering and technology demonstrates the absence of competencies for innovation training. The curricula of the Russian universities do not contain any academic disciplines for teaching innovation as well as there is no definition of “engineering activities”, and “innovation”. Nethertheless the qualification requirements describe some separate components such as R&D, implementation and use of technical and technological innovations implying management of intellectual activity and its results for all occupations, hence mandatory training of bachelor degree students in innovative activities. Materials and Methods: the authors used: a theoretical methods: analysis of philosophical, scientific, technical, engineering, psychological and educational literature; analysis and extrapolation of the research results and teaching experience; modeling of pedagogical situations, analysis of educational standards, foreign and domestic programs of technical training, textbooks and manuals; b scientific methods: generalization, classification, ordering, compare, comparison, modeling; c methods of special research: a system-element method, system-structural and system-functional analysis of the training content, analysis and generalization of pedagogical experience in teaching courses at universities; d experimental and psychology diagnostic methods. Results: the authors developed and implemented the method of teaching engineering students innovative activities based on adding flexible module to core curriculum, a case study of the National Research Mordovia State University. Discussion and Conclusions: the results of the research underscore the significance of the innovation competence by including innovative training module into structure of technical disciplines, as well as specify the

  14. Preliminary design for the Waste Receiving And Processing Facility Module 1: Volume 3, Outline specifications

    International Nuclear Information System (INIS)

    1992-03-01

    This report presents specifications related to the buildings and equipment of the wrap facility. The facility will retrieve, process, and certify transuranic, mixed, and low-level radioactive wastes for disposal

  15. Frequency-specific attentional modulation in human primary auditory cortex and midbrain

    NARCIS (Netherlands)

    Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

    2018-01-01

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning,

  16. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  17. Modulation of ovomucoid-specific oral tolerance in mice fed plant extracts containing lectins

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    We investigated the effect of feeding extracts of four different legumes (red kidney bean (Phaseolus vulgaris), peanut (Arachis hypogaea), soyabean (Glycine max) and pea (Pisum sativum) on the specific immune response against a food protein. Mice were fed ovomucoid and the specific immune response...... influenced the immune response against ovomucoid; however, this was not as pronounced as for kidney bean and was only significant (Ppea extract was fed and peanut extract had a non-significant effect on induction of oral tolerance...... and on the general immune response. Plasma antibodies against kidney-bean lectin, but not against the three other legume lectins, were detected. Our current findings show that other dietary components can influence the specific immune response against food proteins. Various dietary components may thus contribute...

  18. Association of the OPRM1 variant rs1799971 (A118G) with non-specific liability to substance dependence in a collaborative de novo meta-analysis of European-ancestry cohorts

    Science.gov (United States)

    Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M.; Culverhouse, Robert C.; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M.; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N.; Maher, Brion S.; Melroy, Whitney E.; Nelson, Elliot C.; Reid, Mark W.; Robinson, Jason D.; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A.; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A.; Cannon, Dale S.; Cichon, Sven; Corley, Robin P.; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J.; Grucza, Richard A.; Hardin, Jill; Hartmann, Annette M.; Heath, Andrew C.; Herms, Stefan; Hodgkinson, Colin A.; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O.; Johnstone, Elaine; Kaneva, Radka P.; Kendler, Kenneth S.; Kiefer, Falk; Kranzler, Henry R.; Krauter, Ken S.; Levran, Orna; Lucae, Susanne; Lynskey, Michael T.; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G.; Mattheisen, Manuel; Montgomery, Grant W.; Müller-Myhsok, Bertram; Murphy, Michael F.; Neale, Michael C.; Nikolov, Momchil A.; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L.; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J.; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C.; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L.; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W.; Chen, Jingchun; Cinciripini, Paul M.; Edenberg, Howard J; Ehringer, Marissa A.; Ferrell, Robert E.; Gelernter, Joel; Goldman, David; Hewitt, John K.; Hopfer, Christian J.; Iacono, William G.; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M.; Madden, Pamela A.F.; McGue, Matt; Munafò, Marcus R.; Philibert, Robert A.; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T.; Swan, Gary E.; Todorov, Alexandre A.; Vanyukov, Michael M.; Weiss, Robert B.; Bierut, Laura J.; Saccone, Nancy L.

    2015-01-01

    The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for “general” substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day > 20 versus ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83–0.97], p-value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses. PMID:26392368

  19. Social interaction with a tutor modulates responsiveness of specific auditory neurons in juvenile zebra finches.

    Science.gov (United States)

    Yanagihara, Shin; Yazaki-Sugiyama, Yoko

    2018-04-12

    Behavioral states of animals, such as observing the behavior of a conspecific, modify signal perception and/or sensations that influence state-dependent higher cognitive behavior, such as learning. Recent studies have shown that neuronal responsiveness to sensory signals is modified when animals are engaged in social interactions with others or in locomotor activities. However, how these changes produce state-dependent differences in higher cognitive function is still largely unknown. Zebra finches, which have served as the premier songbird model, learn to sing from early auditory experiences with tutors. They also learn from playback of recorded songs however, learning can be greatly improved when song models are provided through social communication with tutors (Eales, 1989; Chen et al., 2016). Recently we found a subset of neurons in the higher-level auditory cortex of juvenile zebra finches that exhibit highly selective auditory responses to the tutor song after song learning, suggesting an auditory memory trace of the tutor song (Yanagihara and Yazaki-Sugiyama, 2016). Here we show that auditory responses of these selective neurons became greater when juveniles were paired with their tutors, while responses of non-selective neurons did not change. These results suggest that social interaction modulates cortical activity and might function in state-dependent song learning. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a.

    Science.gov (United States)

    Yelin-Bekerman, Laura; Elbaz, Idan; Diber, Alex; Dahary, Dvir; Gibbs-Bar, Liron; Alon, Shahar; Lerer-Goldshtein, Tali; Appelbaum, Lior

    2015-10-01

    Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\\wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a (kcnh4a(-/-)) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep.

  1. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

    Science.gov (United States)

    Hay, Colin W; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J; MacKenzie, Alasdair

    2014-09-01

    Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex.

    Science.gov (United States)

    Endo, Toshiaki; Yanagawa, Yuchio; Komatsu, Yukio

    2016-02-01

    To understand the functions of the neocortex, it is essential to characterize the properties of neurons constituting cortical circuits. Here, we focused on a distinct group of GABAergic neurons that are defined by a specific colocalization of intense labeling for both neuronal nitric oxide synthase (nNOS) and substance P (SP) receptor [neurokinin 1 (NK1) receptors]. We investigated the mechanisms of the SP actions on these neurons in visual cortical slices obtained from young glutamate decarboxylase 67-green fluorescent protein knock-in mice. Bath application of SP induced a nonselective cation current leading to depolarization that was inhibited by the NK1 antagonists in nNOS-immunopositive neurons. Ruthenium red and La(3+), transient receptor potential (TRP) channel blockers, suppressed the SP-induced current. The SP-induced current was mediated by G proteins and suppressed by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), but not by inhibitors of phosphatidylinositol-specific PLC, adenylate cyclase or Src tyrosine kinases. Ca(2+) imaging experiments under voltage clamp showed that SP induced a rise in intracellular Ca(2+) that was abolished by removal of extracellular Ca(2+) but not by depletion of intracellular Ca(2+) stores. These results suggest that SP regulates nNOS neurons by activating TRP-like Ca(2+)-permeable nonselective cation channels through a PC-PLC-dependent signaling pathway. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. 41 CFR 102-75.135 - If no hazardous substance activity took place on the property, what specific information must an...

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If no hazardous... DISPOSAL Utilization of Excess Real Property Title Report § 102-75.135 If no hazardous substance activity... hazardous substance activity took place, the reporting agency must include the following statement: The...

  4. Association between alcohol and substance use disorders and all-cause and cause-specific mortality in schizophrenia, bipolar disorder, and unipolar depression

    DEFF Research Database (Denmark)

    Hjorthøj, Carsten; Østergaard, Marie Louise Drivsholm; Benros, Michael Eriksen

    2015-01-01

    BACKGROUND: People with severe mental illness have both increased mortality and are more likely to have a substance use disorder. We assessed the association between mortality and lifetime substance use disorder in patients with schizophrenia, bipolar disorder, or unipolar depression. METHODS: In...

  5. An Estrogen-Responsive Module in the Ventromedial Hypothalamus Selectively Drives Sex-Specific Activity in Females

    Directory of Open Access Journals (Sweden)

    Stephanie M. Correa

    2015-01-01

    Full Text Available Estrogen-receptor alpha (ERα neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

  6. Layer- and Cell Type-Specific Modulation of Excitatory Neuronal Activity in the Neocortex

    Directory of Open Access Journals (Sweden)

    Gabriele Radnikow

    2018-01-01

    Full Text Available From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits.

  7. Modulation of the electrophysiological correlates of retrieval cue processing by the specificity of task demands.

    Science.gov (United States)

    Johnson, Jeffrey D; Rugg, Michael D

    2006-02-03

    Retrieval orientation refers to the differential processing of retrieval cues according to the type of information sought from memory (e.g., words vs. pictures). In the present study, event-related potentials (ERPs) were employed to investigate whether the neural correlates of differential retrieval orientations are sensitive to the specificity of the retrieval demands of the test task. In separate study-test phases, subjects encoded lists of intermixed words and pictures, and then undertook one of two retrieval tests, in both of which the retrieval cues were exclusively words. In the recognition test, subjects performed 'old/new' discriminations on the test items, and old items corresponded to only one class of studied material (words or pictures). In the exclusion test, old items corresponded to both classes of study material, and subjects were required to respond 'old' only to test items corresponding to a designated class of material. Thus, demands for retrieval specificity were greater in the exclusion test than during recognition. ERPs elicited by correctly classified new items in the two types of test were contrasted according to whether words or pictures were the sought-for material. Material-dependent ERP effects were evident in both tests, but the effects onset earlier and offset later in the exclusion test. The findings suggest that differential processing of retrieval cues, and hence the adoption of differential retrieval orientations, varies according to the specificity of the retrieval goal.

  8. From specificity to sensitivity: affective states modulate visual working memory for emotional expressive faces.

    Science.gov (United States)

    Maran, Thomas; Sachse, Pierre; Furtner, Marco

    2015-01-01

    Previous findings suggest that visual working memory (VWM) preferentially remembers angry looking faces. However, the meaning of facial actions is construed in relation to context. To date, there are no studies investigating the role of perceiver-based context when processing emotional cues in VWM. To explore the influence of affective context on VWM for faces, we conducted two experiments using both a VWM task for emotionally expressive faces and a mood induction procedure. Affective context was manipulated by unpleasant (Experiment 1) and pleasant (Experiment 2) IAPS pictures in order to induce an affect high in motivational intensity (defensive or appetitive, respectively) compared to a low arousal control condition. Results indicated specifically increased sensitivity of VWM for angry looking faces in the neutral condition. Enhanced VWM for angry faces was prevented by inducing affects of high motivational intensity. In both experiments, affective states led to a switch from specific enhancement of angry expressions in VWM to an equally sensitive representation of all emotional expressions. Our findings demonstrate that emotional expressions are of different behavioral relevance for the receiver depending on the affective context, supporting a functional organization of VWM along with flexible resource allocation. In VWM, stimulus processing adjusts to situational requirements and transitions from a specifically prioritizing default mode in predictable environments to a sensitive, hypervigilant mode in exposure to emotional events.

  9. From Specificity to Sensitivity: Affective states modulate visual working memory for emotional expressive faces

    Directory of Open Access Journals (Sweden)

    Thomas eMaran

    2015-08-01

    Full Text Available Previous findings suggest that visual working memory preferentially remembers angry looking faces. However, the meaning of facial actions is construed in relation to context. To date, there are no studies investigating the role of perceiver-based context when processing emotional cues in visual working memory. To explore the influence of affective context on visual working memory for faces, we conducted two experiments using both a visual working memory task for emotionally expressive faces and a mood induction procedure. Affective context was manipulated by unpleasant (Experiment 1 and pleasant (Experiment 2 IAPS pictures in order to induce an affect high in motivational intensity (defensive or appetitive, respectively compared to a low arousal control condition. Results indicated specifically increased sensitivity of visual working memory for angry looking faces in the neutral condition. Enhanced visual working memory for angry faces was prevented by inducing affects of high motivational intensity. In both experiments, affective states led to a switch from specific enhancement of angry expressions in visual working memory to an equally sensitive representation of all emotional expressions. Our findings demonstrate that emotional expressions are of different behavioral relevance for the receiver depending on the affective context, supporting a functional organization of visual working memory along with flexible resource allocation. In visual working memory, stimulus processing adjusts to situational requirements and transitions from a specifically prioritizing default mode in predictable environments to a sensitive, hypervigilant mode in exposure to emotional events.

  10. Laminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.

    Science.gov (United States)

    Merna, Nick; Wong, Andrew K; Barahona, Victor; Llanos, Pierre; Kunar, Balvir; Palikuqi, Brisa; Ginsberg, Michael; Rafii, Shahin; Rabbany, Sina Y

    2018-04-17

    Endothelial cells form vascular beds in all organs and are exposed to a range of mechanical forces that regulate cellular phenotype. We sought to determine the role of endothelial luminal surface stiffness in tissue-specific mechanotransduction of laminar shear stress in microvascular mouse cells and the role of arachidonic acid in mediating this response. Microvascular mouse endothelial cells were subjected to laminar shear stress at 4 dynes/cm 2 for 12 hours in parallel plate flow chambers that enabled real-time optical microscopy and atomic force microscopy measurements of cell stiffness. Lung endothelial cells aligned parallel to flow, while cardiac endothelial cells did not. This rapid alignment was accompanied by increased cell stiffness. The addition of arachidonic acid to cardiac endothelial cells increased alignment and stiffness in response to shear stress. Inhibition of arachidonic acid in lung endothelial cells and embryonic stem cell-derived endothelial cells prevented cellular alignment and decreased cell stiffness. Our findings suggest that increased endothelial luminal surface stiffness in microvascular cells may facilitate mechanotransduction and alignment in response to laminar shear stress. Furthermore, the arachidonic acid pathway may mediate this tissue-specific process. An improved understanding of this response will aid in the treatment of organ-specific vascular disease. © 2018 John Wiley & Sons Ltd.

  11. Frequency-specific modulation of population-level frequency tuning in human auditory cortex

    Directory of Open Access Journals (Sweden)

    Roberts Larry E

    2009-01-01

    Full Text Available Abstract Background Under natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random under auditory focused attention by means of magnetoencephalography (MEG. Results In total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands. Conclusion The present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

  12. The European DISABKIDS project: development of seven condition-specific modules to measure health related quality of life in children and adolescents

    Directory of Open Access Journals (Sweden)

    Bullinger Monika

    2005-11-01

    Full Text Available Abstract Background The European DISABKIDS project aims to enhance the Health Related Quality of Life (HRQoL of children and adolescents with chronic medical conditions and their families. We describe the development of the seven cross-nationally tested condition-specific modules of the European DISABKIDS HRQoL instrument in a population of children and adolescents. The condition-specific modules are intended for use in conjunction with the DISABKIDS chronic generic module. Methods Focus groups were used to construct the pilot version of the DISABKIDS condition-specific HRQoL modules for asthma, juvenile idiopathic arthritis, atopic dermatitis, cerebral palsy, cystic fibrosis, diabetes and epilepsy. Analyses were conducted on pilot test data in order to construct field test versions of the modules. A series of factor analyses were run, first, to determine potential structures for each condition-specific module, and, secondly, to select a reduced number of items from the pilot test to be included in the field test. Post-field test analyses were conducted to retest the domain structure for the final DISABKIDS condition-specific modules. Results The DISABKIDS condition-specific modules were tested in a pilot study of 360 respondents, and subsequently in a field test of 1152 respondents in 7 European countries. The final condition-specific modules consist of an 'Impact' domain and an additional domain (e.g. worry, stigma, treatment with between 10 to 12 items in total. The Cronbach's alpha of the final domains was found to vary from 0.71 to 0.90. Conclusion The condition-specific modules of the DISABKIDS instrument were developed through a step-by-step process including cognitive interview, clinical expertise, factor analysis, correlations and internal consistency. A cross-national pilot and field test were necessary to collect these data. In general, the internal consistency of the domains was satisfactory to high. In future, the DISABKIDS

  13. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

    Directory of Open Access Journals (Sweden)

    Girgis Hani Z

    2012-02-01

    Full Text Available Abstract Background Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF binding sites (TFBSs. Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. Results We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was

  14. Determination of the element-specific complex permittivity using a soft x-ray phase modulator

    Science.gov (United States)

    Kubota, Y.; Hirata, Y.; Miyawaki, J.; Yamamoto, S.; Akai, H.; Hobara, R.; Yamamoto, Sh.; Yamamoto, K.; Someya, T.; Takubo, K.; Yokoyama, Y.; Araki, M.; Taguchi, M.; Harada, Y.; Wadati, H.; Tsunoda, M.; Kinjo, R.; Kagamihata, A.; Seike, T.; Takeuchi, M.; Tanaka, T.; Shin, S.; Matsuda, I.

    2017-12-01

    We report on directly determining the complex permittivity tensor using a method combining a developed light source from a segmented cross undulator of synchrotron radiation and the magneto-optical Kerr effect. The empirical permittivity, which carries the electronic and magnetic information of a material, has element specificity and has perfect confirmation using the quantum-mechanical calculation for itinerant electrons systems. These results help in understanding the interaction of light and matter, and they provide an interesting approach to seek the best materials as optical elements, for example, in extended-ultraviolet lithographic technologies or in state-of-the-art laser technologies.

  15. α--AMYLASES OF Aspergillus flavus var. oryzae AND Bacillus subtilis: THE SUBSTRATE SPECIFICITY AND RESISTANCE TO A NUMBER OF CHEMICALLY ACTIVE SUBSTANCES

    Directory of Open Access Journals (Sweden)

    K. V. Avdiyuk

    2013-06-01

    Full Text Available The ability of Aspergillus flavus var. oryzae 80428 and Bacillus subtilis 147 α-amylases to split different carbohydrate-containing substrates, such as maltose, sucrose, trehalose, dextrin, α- and β-cyclodextrin, amylose, amylopectin, glycogen, pullulan, soluble starch, insoluble starch, corn starch, wheat starch, dextran 500 has been studied. It was shown that investigated enzymes differ by substrate specificity. α-Amylase of A. flavus var. oryzae 80428 rapidly hydrolysed soluble potato and wheat starch, while the α-amylase of B. subtilis 147 — only wheat starch. Both enzymes don’t cleave maltose, α-cyclodextrin and dextran 500. A. flavus var. oryzae 80428 α-amylase display very small ability to hydrolyze pullulan, while α-amylase of B. subtilis 147 it does not act in general. The lowest values of Michaelis constant for both enzymes at splitting of glycogen have been obtained, indicating that enzymes have the greatest affinity to this substrate. The studies of influence of chemically active substances on activity of A. flavus var. oryzae 80428 and B. subtilis 147 ?-amylases show there are resistant to urea, deoxycholic acid, Tween-80, Triton X-100 and hydrogen peroxide. It’s indicate the enzymes tested may be competitive in compare with earlier described in literature enzymes. The obtained results give a possibility to propose in future usage these enzymes in different fields of industry, foremost in detergent industry.

  16. Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan?

    Science.gov (United States)

    Brown-Borg, Holly M; Buffenstein, Rochelle

    2017-10-01

    With few exceptions, nutritional and dietary interventions generally impact upon both old-age quality of life and longevity. The life prolonging effects, commonly observed with dietary restriction reportedly are linked to alterations in protein intake and specifically limiting the dietary intake of certain essential amino acids. There is however a paucity of data methodically evaluating the various essential amino acids on health- and lifespan and the mechanisms involved. Rodent diets containing either lower methionine content, or tryptophan, than that found in commercially available chow, appear to elicit beneficial effects. It is unclear whether all of these favorable effects associated with restricted intake of methionine and tryptophan are due to their specific unique properties or if restriction of other essential amino acids, or proteins in general, may produce similar results. Considerably more work remains to be done to elucidate the mechanisms by which limiting these vital molecules may delay the onset of age-associated diseases and improve quality of life at older ages. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Hazard Analysis of Software Requirements Specification for Process Module of FPGA-based Controllers in NPP

    Energy Technology Data Exchange (ETDEWEB)

    Jung; Sejin; Kim, Eui-Sub; Yoo, Junbeom [Konkuk University, Seoul (Korea, Republic of); Keum, Jong Yong; Lee, Jang-Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Software in PLC, FPGA which are used to develop I and C system also should be analyzed to hazards and risks before used. NUREG/CR-6430 proposes the method for performing software hazard analysis. It suggests analysis technique for software affected hazards and it reveals that software hazard analysis should be performed with the aspects of software life cycle such as requirements analysis, design, detailed design, implements. It also provides the guide phrases for applying software hazard analysis. HAZOP (Hazard and operability analysis) is one of the analysis technique which is introduced in NUREG/CR-6430 and it is useful technique to use guide phrases. HAZOP is sometimes used to analyze the safety of software. Analysis method of NUREG/CR-6430 had been used in Korea nuclear power plant software for PLC development. Appropriate guide phrases and analysis process are selected to apply efficiently and NUREG/CR-6430 provides applicable methods for software hazard analysis is identified in these researches. We perform software hazard analysis of FPGA software requirements specification with two approaches which are NUREG/CR-6430 and HAZOP with using general GW. We also perform the comparative analysis with them. NUREG/CR-6430 approach has several pros and cons comparing with the HAZOP with general guide words and approach. It is enough applicable to analyze the software requirements specification of FPGA.

  18. [Immunotoxicity and environmental substances].

    Science.gov (United States)

    Teshima, Reiko

    2014-01-01

    A well functioning immune system is essential in maintaining integrity of the organism, and malfunction may have severe health consequences. Environmental substances may pose direct toxicity to components of the immune system, often leading to immunosuppression and resulting reduced resistance to infections and tumors. Alternatively, such substances may be recognized by the immune system in a specific fashion, which may result in allergy and autoimmunity. A proper risk assessment of environmental substances in terms of immunotoxicity is necessary. In this manuscript, I reviewed recent three topics about immunotoxicity: (1) IPCS/WHO Guidance for immunotoxicity risk assessment for chemicals, (2) Intestinal immunotoxicity, and (3) Epicutaneous sensitization of food proteins.

  19. Allergen specific responses in cord and adult blood are differentially modulated in the presence of endotoxins

    DEFF Research Database (Denmark)

    Eiwegger, T.; Mayer, E.; Pedersen, Susanne Brix

    2008-01-01

    Background Endotoxins are common contaminants in allergen preparations and affect antigen-specific cellular responses. Distinct effects of endotoxin on cells in human umbilical cord and adult blood are poorly defined. Objectives To examine the effect of endotoxins in allergen preparations...... on cellular responses in human cord and peripheral blood (PB). Methods The endotoxin content in beta lactoglobulin (BLG), the peanut allergen Ara h 1 and the major birch pollen allergen Bet v 1 was assessed. Proliferation and cytokine response of mononuclear cells towards contaminated and lipopolysaccharide....... Results The proliferative response of cord blood (CB)-derived mononuclear cells towards allergen-preparations at day 3 was related to the level of LPS contamination. At day 7, proliferation was also detected in the absence of endotoxin. Cytokine production in CB was strongly affected by the content...

  20. Brain-specific modulation of kynurenic acid synthesis in the rat

    DEFF Research Database (Denmark)

    Gramsbergen, J B; Hodgkins, P S; Rassoulpour, A

    1997-01-01

    adult cerebral cortex, veratridine, quisqualate, and L-alpha-aminoadipate decreased kynurenate synthesis substantially. Glucose removal or changes in the ionic milieu, too, influenced kynurenate formation significantly, suggesting that demands on cellular energy interfere with kynurenate production...... tissue, indicating its dependency on intact neuron-glia interactions. Compared with the normal adult brain, ionic manipulations yielded qualitatively distinct results in the developing brain and in the periphery, but their effects remained unchanged in the lesioned striatum. Glucose deprivation was less...... consequential in the immature than in the adult brain and was entirely ineffective in the lesioned striatum and in the periphery. These results further link cellular, especially astrocytic, energy metabolism to kynurenate formation in the brain. More generally, the existence of brain-specific mechanisms...

  1. A space oddity: geographic and specific modulation of migration in Eudyptes penguins.

    Science.gov (United States)

    Thiebot, Jean-Baptiste; Cherel, Yves; Crawford, Robert J M; Makhado, Azwianewi B; Trathan, Philip N; Pinaud, David; Bost, Charles-André

    2013-01-01

    Post-breeding migration in land-based marine animals is thought to offset seasonal deterioration in foraging or other important environmental conditions at the breeding site. However the inter-breeding distribution of such animals may reflect not only their optimal habitat, but more subtle influences on an individual's migration path, including such factors as the intrinsic influence of each locality's paleoenvironment, thereby influencing animals' wintering distribution. In this study we investigated the influence of the regional marine environment on the migration patterns of a poorly known, but important seabird group. We studied the inter-breeding migration patterns in three species of Eudyptes penguins (E. chrysolophus, E. filholi and E. moseleyi), the main marine prey consumers amongst the World's seabirds. Using ultra-miniaturized logging devices (light-based geolocators) and satellite tags, we tracked 87 migrating individuals originating from 4 sites in the southern Indian Ocean (Marion, Crozet, Kerguelen and Amsterdam Islands) and modelled their wintering habitat using the MADIFA niche modelling technique. For each site, sympatric species followed a similar compass bearing during migration with consistent species-specific latitudinal shifts. Within each species, individuals breeding on different islands showed contrasting migration patterns but similar winter habitat preferences driven by sea-surface temperatures. Our results show that inter-breeding migration patterns in sibling penguin species depend primarily on the site of origin and secondly on the species. Such site-specific migration bearings, together with similar wintering habitat used by parapatrics, support the hypothesis that migration behaviour is affected by the intrinsic characteristics of each site. The paleo-oceanographic conditions (primarily, sea-surface temperatures) when the populations first colonized each of these sites may have been an important determinant of subsequent migration

  2. A space oddity: geographic and specific modulation of migration in Eudyptes penguins.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Thiebot

    Full Text Available Post-breeding migration in land-based marine animals is thought to offset seasonal deterioration in foraging or other important environmental conditions at the breeding site. However the inter-breeding distribution of such animals may reflect not only their optimal habitat, but more subtle influences on an individual's migration path, including such factors as the intrinsic influence of each locality's paleoenvironment, thereby influencing animals' wintering distribution. In this study we investigated the influence of the regional marine environment on the migration patterns of a poorly known, but important seabird group. We studied the inter-breeding migration patterns in three species of Eudyptes penguins (E. chrysolophus, E. filholi and E. moseleyi, the main marine prey consumers amongst the World's seabirds. Using ultra-miniaturized logging devices (light-based geolocators and satellite tags, we tracked 87 migrating individuals originating from 4 sites in the southern Indian Ocean (Marion, Crozet, Kerguelen and Amsterdam Islands and modelled their wintering habitat using the MADIFA niche modelling technique. For each site, sympatric species followed a similar compass bearing during migration with consistent species-specific latitudinal shifts. Within each species, individuals breeding on different islands showed contrasting migration patterns but similar winter habitat preferences driven by sea-surface temperatures. Our results show that inter-breeding migration patterns in sibling penguin species depend primarily on the site of origin and secondly on the species. Such site-specific migration bearings, together with similar wintering habitat used by parapatrics, support the hypothesis that migration behaviour is affected by the intrinsic characteristics of each site. The paleo-oceanographic conditions (primarily, sea-surface temperatures when the populations first colonized each of these sites may have been an important determinant of

  3. Frequency specificity and left-ear advantage of medial olivocochlear efferent modulation: a study based on stimulus frequency otoacoustic emission.

    Science.gov (United States)

    Xing, Dongjia; Gong, Qin

    2017-09-06

    The medial olivocochlear (MOC) bundle is an auditory nucleus that projects efferent nerve fibers to the outer hair cells (OHCs) for synaptic innervation. The aim of the present study was to investigate the possible existence of frequency and ear specificity in MOC efferent modulation, as well as how MOC activation influences cochlear tuning. Stimulus frequency otoacoustic emissions (SFOAEs) were used to study MOC efferent modulation. Therefore, the current experiment was designed to compare the degree of SFOAE suppression in the both ears of 20 individuals at 1, 2, 4, and 8 kHz. We also compared changes in Q10 values of SFOAE suppression tuning curves at 1, 2, and 4 kHz under contralateral acoustic stimulation (CAS) and no-CAS conditions. We observed a significant reduction in SFOAE magnitude in the CAS condition compared with the no-CAS condition at 1 and 2 kHz in the left ear. A significant difference in CAS suppression was also found between the left and right ears at 1 and 2 kHz, with larger CAS suppression in the left ear. CAS further produced a statistically significant increase in the Q10 value at 1 kHz and a significant reduction in Q10 values at 2 and 4 kHz. These findings suggest a left-ear advantage in terms of CAS-induced MOC efferent SFOAE suppression, with larger MOC efferent modulation for lower frequencies, and cochlear tuning was sharpened by means of MOC activation at lower frequencies and broadened at higher frequencies.

  4. The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.

    Science.gov (United States)

    Grants, Jennifer M; Ying, Lisa T L; Yoda, Akinori; You, Charlotte C; Okano, Hideyuki; Sawa, Hitoshi; Taubert, Stefan

    2016-02-01

    Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals. Copyright © 2016 by the Genetics Society of America.

  5. Modulation of differentiation and self-renewal of tissue specific stem cells for effective mitigation of radiation injury

    International Nuclear Information System (INIS)

    Bandekar, Mayuri; Patwardhan, R.S.; Maurya, Dharmendra K.; Bhilwade, Hari N.; Sharma, Deepak; Sandur, Santosh Kumar

    2017-01-01

    The use of stem cells in regenerative medicine for the treatment of various human diseases is one of the active research areas. The aim of regenerative medicine is to restore normal tissue functions by replenishing injured tissues using either cell-based therapy or by inducing certain factors that can aid endogenous repair and regeneration. The approach for inducing endogenous repair and regeneration requires in vivo modulation of tissue-specific stem cells by therapeutic agents and enhance their abundance through activation, proliferation, differentiation, or reprogramming. Here we describe three different approaches to enhance the abundance of hematopoietic stem cells in vivo for mitigation of radiation induced toxicity. Baicalein, a flavonoid derived from Chinese and Indian medicinal plants like Scutellaria baicalensis and Terminalia ariuna enhanced the abundance of hematopoietic stem cells through activation of Nrf-2 in the lineage negative cells. Another anti-oxidant, chlorophyllin derived from green plant pigment, chlorophyll also enhanced the abundance of hematopoietic stem cells through modulation of cell cycle in cells of the bone marrow. Treatment of mice with Cobaltus chloride (CoCl_2), a well-known activator of hypoxia inducible factor-1α (HIP-1α), also led to increase in the number of hematopoietic stem cells in the bone marrow. Whereas chlorophyllin offered up to 100 % protection against whole body irradiation (WBI, 8 Gy) induced mortality in mice, baicalein offered up to70%protection. Cobaltus chloride treatment offered 40% protection against 8 Gy of WBI. These studies indicate potential use of stem cell modulating agents as effective mitigators of radiation induced toxicity in vivo. (author)

  6. An electronic screen for triaging adolescent substance use by risk levels.

    Science.gov (United States)

    Levy, Sharon; Weiss, Roger; Sherritt, Lon; Ziemnik, Rosemary; Spalding, Allegra; Van Hook, Shari; Shrier, Lydia A

    2014-09-01

    Screening adolescents for substance use and intervening immediately can reduce the burden of addiction and substance-related morbidity. Several screening tools have been developed to identify problem substance use for adolescents, but none have been calibrated to triage adolescents into clinically relevant risk categories to guide interventions. To describe the psychometric properties of an electronic screen and brief assessment tool that triages adolescents into 4 actionable categories regarding their experience with nontobacco substance use. Adolescent patients (age range, 12-17 years) arriving for routine medical care at 2 outpatient primary care centers and 1 outpatient center for substance use treatment at a pediatric hospital completed an electronic screening tool from June 1, 2012, through March 31, 2013, that consisted of a question on the frequency of using 8 types of drugs in the past year (Screening to Brief Intervention). Additional questions assessed severity of any past-year substance use. Patients completed a structured diagnostic interview (Composite International Diagnostic Interview-Substance Abuse Module), yielding Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) substance use diagnoses. For the entire screen and the Screening to Brief Intervention, sensitivity and specificity for identifying nontobacco substance use, substance use disorders, severe substance use disorders, and tobacco dependence were calculated using the Composite International Diagnostic Interview-Substance Abuse Module as the criterion standard. Of 340 patients invited to participate, 216 (63.5%) enrolled in the study. Sensitivity and specificity were 100% and 84% (95% CI, 76%-89%) for identifying nontobacco substance use, 90% (95% CI, 77%-96%) and 94% (95% CI, 89%-96%) for substance use disorders, 100% and 94% (95% CI, 90%-96%) for severe substance use disorders, and 75% (95% CI, 52%-89%) and 98% (95% CI, 95%-100%) for nicotine dependence. No significant

  7. Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder

    Directory of Open Access Journals (Sweden)

    Thomas Hassa

    2017-01-01

    Full Text Available Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

  8. Cholinergic Modulation of Cortical Microcircuits Is Layer-Specific: Evidence from Rodent, Monkey and Human Brain

    Directory of Open Access Journals (Sweden)

    Joshua Obermayer

    2017-12-01

    Full Text Available Acetylcholine (ACh signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence. From recent discoveries in the mouse, rat, monkey and human brain, a picture emerges in which the basal forebrain (BF cholinergic system targets the neocortex with much more spatial and temporal detail than previously considered. Fast cholinergic synapses acting on a millisecond time scale are abundant in the mammalian cerebral cortex, and provide BF cholinergic neurons with the possibility to rapidly alter information flow in cortical microcircuits. Finally, recent studies have outlined novel mechanisms of how cholinergic projections from the BF affect synaptic strength in several brain areas of the rodent brain, with behavioral consequences. This review highlights these exciting developments and discusses how these findings translate to human brain circuitries.

  9. Modality-specific alpha modulations facilitate long-term memory encoding in the presence of distracters.

    Science.gov (United States)

    Jiang, Haiteng; van Gerven, Marcel A J; Jensen, Ole

    2015-03-01

    It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it reflects the functional disengagement of specific regions in attention and memory tasks. We here ask if such allocation of resources by alpha oscillations generalizes to long-term memory encoding in a cross-modal setting in which we acquired the ongoing brain activity using magnetoencephalography. Participants were asked to encode pictures while ignoring simultaneously presented words and vice versa. We quantified the brain activity during rehearsal reflecting subsequent memory in the different attention conditions. The key finding was that successful long-term memory encoding is reflected by alpha power decreases in the sensory region of the to-be-attended modality and increases in the sensory region of the to-be-ignored modality to suppress distraction during rehearsal period. Our results corroborate related findings from attention studies by demonstrating that alpha activity is also important for the allocation of resources during long-term memory encoding in the presence of distracters.

  10. Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance

    Directory of Open Access Journals (Sweden)

    Tomoaki Naito

    2017-10-01

    Full Text Available We identified a crypt-specific core microbiota (CSCM dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas. Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS, through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage.

  11. Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.

    Directory of Open Access Journals (Sweden)

    Stefan M Ivanov

    Full Text Available An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

  12. Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.

    Science.gov (United States)

    Ivanov, Stefan M; Cawley, Andrew; Huber, Roland G; Bond, Peter J; Warwicker, Jim

    2017-01-01

    An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

  13. Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder.

    Science.gov (United States)

    Hassa, Thomas; Sebastian, Alexandra; Liepert, Joachim; Weiller, Cornelius; Schmidt, Roger; Tüscher, Oliver

    2017-01-01

    Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

  14. Plasma protein corona modulates the vascular wall interaction of drug carriers in a material and donor specific manner.

    Directory of Open Access Journals (Sweden)

    Daniel J Sobczynski

    Full Text Available The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid (PLGA spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.

  15. Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity*

    Science.gov (United States)

    Jin, Lily L.; Wybenga-Groot, Leanne E.; Tong, Jiefei; Taylor, Paul; Minden, Mark D.; Trudel, Suzanne; McGlade, C. Jane; Moran, Michael F.

    2015-01-01

    Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y194 impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y194 on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases. PMID:25587033

  16. Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its binding affinity and specificity.

    Science.gov (United States)

    Jin, Lily L; Wybenga-Groot, Leanne E; Tong, Jiefei; Taylor, Paul; Minden, Mark D; Trudel, Suzanne; McGlade, C Jane; Moran, Michael F

    2015-03-01

    Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. The hippocampus as a "stupid," domain-specific module: Implications for theories of recent and remote memory, and of imagination.

    Science.gov (United States)

    Moscovitch, Morris

    2008-03-01

    The hippocampus and surrounding regions of the medial temporal lobe play a central role in all neuropsychological theories of memory. It is still a matter of debate, however, how best to characterise the functions of these regions, the hippocampus in particular. In this article, I examine the proposal that the hippocampus is a "stupid" module whose specific domain is consciously apprehended information. A number of interesting consequences for the organisation of memory and the brain follow from this proposal and the assumptions it entails. These, in turn, have important implications for neuropsychological theories of recent and remote episodic, semantic, and spatial memory and for the functions that episodic memory may serve in perception, comprehension, planning, imagination, and problem solving. I consider these implications by selectively reviewing the literature and primarily drawing on research my collaborators and I have conducted. Copyright (c) 2008 APA, all rights reserved.

  18. Nitric Oxide Binds to and Modulates the Activity of a Pollen Specific Arabidopsis Diacylglycerol Kinase

    KAUST Repository

    Wong, Aloysius Tze

    2014-06-01

    NO responses. Specifically, the mis-expressing atdgk4 pollen tubes have growth rates that were less affected by NO and showed reduced bending angles when challenged by an NO source. Further works on atdgk4 knockout/knockdown mutants will reveal the biological functions of ATDGK4 in NO and/or cGMP signaling in the pollen, and in the broader fertilization process.

  19. miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity.

    Science.gov (United States)

    Li, Bo; Wang, Xi; Choi, In Young; Wang, Yu-Chen; Liu, Siyuan; Pham, Alexander T; Moon, Heesung; Smith, Drake J; Rao, Dinesh S; Boldin, Mark P; Yang, Lili

    2017-10-02

    Autoreactive CD4 T cells that differentiate into pathogenic Th17 cells can trigger autoimmune diseases. Therefore, investigating the regulatory network that modulates Th17 differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive Th17 cells and organ-specific autoimmunity remains largely unknown. Here, we have reported that miR-146a-deficient mice developed more severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). We bred miR-146a-deficient mice with 2D2 T cell receptor-Tg mice to generate 2D2 CD4 T cells that are deficient in miR-146a and specific for myelin oligodendrocyte glycoprotein (MOG), an autoantigen in the EAE model. miR-146a-deficient 2D2 T cells induced more severe EAE and were more prone to differentiate into Th17 cells. Microarray analysis revealed enhancements in IL-6- and IL-21-induced Th17 differentiation pathways in these T cells. Further study showed that miR-146a inhibited the production of autocrine IL-6 and IL-21 in 2D2 T cells, which in turn reduced their Th17 differentiation. Thus, our study identifies miR-146a as an important molecular brake that blocks the autocrine IL-6- and IL-21-induced Th17 differentiation pathways in autoreactive CD4 T cells, highlighting its potential as a therapeutic target for treating autoimmune diseases.

  20. STEPS: source term estimation based on plant status phase 0 - the technical specifications of the containment module

    International Nuclear Information System (INIS)

    Vamanu, D.V.

    1998-01-01

    In the framework of Project RODOS (Real-Time On-Line Decision Support System for Nuclear Emergencies in Europe), the European Atomic Energy Community (EAEC) of the Commission of the European Communities has commissioned the development of a unified concept, body of knowledge, models and software package meant to assist the evaluation of the source term of severe nuclear accidents in light water reactors of the types prevailing on the Continent. Code-named STEPS, for 'Source Term Estimation based on Plant Status', the project has evolved as Contract RODOS D (FI4P-CT96-0048), between EAEC and consortium of expert European centres including Commissariat a l'Energie Atomique, Institut de Protection et de Surete Nucleaire, (CEA-DPI-SEAC) as Coordinator and Forschungszentrum Karlsruhe GmbH (FZK-INR), the Finnish Centre for Radiation and Nuclear Safety, (STUK-NSD), the Technical Research Centre of Finland, Energy, Nuclear Energy (VTT-ET-NE), and Eidgenossische Technische Hochschule - ETH Zurich, Centre of Excellence (ETH-CERS) as Contractors. For the Phase 0 of the project, an IFIN-HH expert has been assigned by ETH-CERS to develop the Technical Specifications of the delivery component of the intended STEPS package, the CONTAINMENT Module. Sponsored by ETH-CERS headquarters in Zurich, the work was done on the premises and with the logistic support of CEA D PI-SEAC at Fontenay-aux-Roses, with the feedback processing and computer code development subsequently performed in Bucharest. The Technical Specifications of the STEPS CONTAINMENT Module were guided by specific terms of reference, including: (i) the capability of the software to function as a source term interface between targeted nuclear power plants and the RODOS System; (ii) the comparable capability of the system to be operated as a stand-alone assessment and decision support tool for a comprehensive variety of plants, nuclear emergency classes. On the technical side, the specifications had to focus on the possible

  1. Study of a method for reducing fuel consumption and the amount of specific emissions of harmful substances with exhaust gases of passenger cars when using the “climate control” system

    Science.gov (United States)

    Burakova, L. N.; Anisimov, I. A.; Burakova, A. D.; Burakova, O. D.

    2018-05-01

    The article deals with the issue of improving the fuel economy and environmental friendliness of motor vehicles which serve the administrative and management personnel of the oil and gas industry. It is established that fuel consumption and the amount of specific emissions of harmful substances with exhaust gases of cars when using the “climate control” system depend on the effective ambient temperature, the color of the opaque car body elements, the power of the car engine and the interior volume. However, the simplest controlled factor is the color of the opaque car body elements, which is characterized by the coefficient of light reflection. In the course of experimental studies, we established the dependences of a change in fuel consumption and a share of reducing emissions of harmful substances with exhaust gases of passenger cars with the “climate control” system on the coefficient of light reflection. A method has been developed to reduce fuel consumption and the amount of specific emissions of harmful substances with the exhaust gases of passenger cars using the “climate control” system, which involves painting the vehicle roof white and allows reducing fuel consumption by 5.5-10.3%, and the amount of specific emissions of harmful substances by 0.8-2.3%.

  2. Specific features of design and electric circuit of the pulse modulator of the amplification channel of second-section linear accelerator for a meson factory

    International Nuclear Information System (INIS)

    Dyukov, L.V.; Fedorov, A.F.; Terekhov, V.F.

    1977-01-01

    The circuit and design of a modulator at pulse power of 15 MW and average power of 300 kW, intended for supplying a klystron generator, are described. The modulator is designed for operating in a lengthy mode. The capacitance storage-former is made in the form of three parallel sections of artificial shaping lines in order to lower the specific loads on the elements of the shaping line and thyristors. The thyristor spark gaps are made in the form of a unified water-cooled assembly composed of 12 series TD-320 thyristors. An assessment of the modulator reliability has shown that the average time-to-fault is 800 hr. Modulator tests confirm that the choice of the circuit solution is correct. The modulator total efficiency equals to approximately 0.9

  3. Bioactive substances

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.

    Chemistry related to certain bioactive molecules, from Indian Ocean Region, developed into drugs or which served as models for the synthesis of more effective bioactive substances or in use in fundamental studies of physiological and biochemical...

  4. Psychotoxic Substances

    Science.gov (United States)

    1964-11-16

    halluci- nations , disturbances of body perception, depersonalization symptoms, and a "psychotic" status. Also with the derivatives, the individual...the substance had also local anesthetic properties. After clinical testing, ibogaine was then used as stimulans for neurasthenics and convalescents1 1 3...con- siderably disturbed by this group of substances. The optic halluci- nations consist to a small extent in scenic proceedings of actions, more

  5. Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2014-10-01

    Full Text Available The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs. To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

  6. Subregion-specific modulation of excitatory input and dopaminergic output in the striatum by tonically activated glycine and GABAA receptors

    Directory of Open Access Journals (Sweden)

    Louise eAdermark

    2011-10-01

    Full Text Available The flow of cortical information through the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing. The striatum is the biggest input nucleus to the basal ganglia and the aim of this study was to assess the role of inhibitory GABAA and glycine receptors in regulating synaptic activity in the dorsolateral (DLS and ventral striatum (nucleus accumbens, nAc. Local field potential recordings from coronal brain slices of juvenile and adult Wistar rats showed that GABAA receptors and strychnine-sensitive glycine receptors are tonically activated and inhibit excitatory input to the DLS and to the nAc. Strychnine-induced disinhibition of glutamatergic transmission was insensitive to the muscarinic receptor inhibitor scopolamine (10 µM, inhibited by the nicotinic acetylcholine receptor antagonist mecamylamine (10 µM and blocked by GABAA receptor inhibitors, suggesting that tonically activated glycine receptors depress excitatory input to the striatum through modulation of cholinergic and GABAergic neurotransmission. As an end-product example of striatal GABAergic output in vivo we measured dopamine release in the DLS and nAc by microdialysis in the awake and freely moving rat. Reversed dialysis of bicuculline (50 μM in perfusate only increased extrasynaptic dopamine levels in the nAc, while strychnine administered locally (200 μM in perfusate decreased dopamine output by 60% in both the DLS and nAc. Our data suggest that GABAA and glycine receptors are tonically activated and modulate striatal transmission in a partially sub-region specific manner.

  7. Effective Design and Planning Specification of Low Impact Development Practices Using Water Management Analysis Module (WMAM: Case of Malaysia

    Directory of Open Access Journals (Sweden)

    Kamal Ahmed

    2017-02-01

    Full Text Available Developers are increasingly looking for the best management practices to reduce the risk of floods in rapidly growing urban areas. Low impact development (LID is regarded as one of the most suitable solutions for urban stormwater management and thus the U.S. EPA’s (Environmental Protection Agency SWMM5.1 (Storm Water Management Model added the hydrological simulation function for LID structures in 2009. However, SWMM5.1 cannot consider the optimal or best physical specifications of LID design and planning fitted to a study area, nor can it instantly derive the best combination for multiple LID designs and plans. Therefore, in this study, a web-based decision support system (DSS for the EPA’s SWMM 5.1, referred to as the Water Management Analysis Module (WMAM is used to decide the most effective specifications of design and planning parameters for LID structure. This study was carried out over an urban catchment of University Technology Malaysia campus located in Johor, Malaysia. The hydrologic cycles with and without LID were simulated using EPA SWMM5.1. The sensitivity analysis and multiple scenario analysis were performed using WMAM. As a result, the effective specification of LID design parameters indicates that peak flow is reduced to 20.95% and 17.5% for two sub-catchments, S1 (highest by area and S6 (lowest by area by installing an LID structure. Thus, this study provides a tool for the best solution for what values for physical parameters will be the best for a specified LID type and what capacities can achieve the particular objectives using WMAM.

  8. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones

    OpenAIRE

    Hay, Colin W.; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J.; MacKenzie, Alasdair

    2014-01-01

    Summary Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Usi...

  9. Intensity modulated radiation therapy: Analysis of patient specific quality control results, experience of Rene-Gauducheau Centre; Radiotherapie conformationnelle avec modulation d'intensite: analyse des resultats des controles precliniques, experience du centre Rene-Gauducheau

    Energy Technology Data Exchange (ETDEWEB)

    Chiavassa, S.; Brunet, G.; Gaudaire, S.; Munos-Llagostera, C.; Delpon, G.; Lisbona, A. [Service de physique medicale, centre Rene-Gauducheau, CLCC Nantes Atlantique, site hospitalier Nord, boulevard Jacques-Monod, 44805 Nantes Saint-Herblain cedex (France)

    2011-07-15

    Purpose. - Systematic verifications of patient's specific intensity-modulated radiation treatments are usually performed with absolute and relative measurements. The results constitute a database which allows the identification of potential systematic errors. Material and methods. - We analyzed 1270 beams distributed in 232 treatment plans. Step-and-shoot intensity-modulated radiation treatments were performed with a Clinac (6 and 23 MV) and sliding window intensity-modulated radiation treatments with a Novalis (6 MV). Results. - The distributions obtained do not show systematic error and all the control meet specified tolerances. Conclusion. - These results allow us to reduce controls specific patients for treatments performed under identical conditions (location, optimization and segmentation parameters of treatment planning system, etc.). (authors)

  10. Normalization of prostate specific antigen in patients treated with intensity modulated radiotherapy for clinically localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Schmitz Matthew D

    2010-09-01

    Full Text Available Abstract Background The purpose of this study was to determine the expected time to prostate specific antigen (PSA normalization with or without neoadjuvant androgen deprivation (NAAD therapy after treatment with intensity modulated radiotherapy (IMRT for patients with clinically localized prostate cancer. Methods A retrospective cohort research design was used. A total of 133 patients with clinical stage T1c to T3b prostate cancer (2002 AJCC staging treated in a community setting between January 2002 and July 2005 were reviewed for time to PSA normalization using 1 ng/mL and 2 ng/mL as criteria. All patients received IMRT as part of their management. Times to PSA normalization were calculated using the Kaplan-Meier method. Significance was assessed at p Results Fifty-six of the 133 patients received NAAD (42.1%. Thirty-one patients (23.8% received radiation to a limited pelvic field followed by an IMRT boost, while 99 patients received IMRT alone (76.2%. The times to serum PSA normalization 0.05, and 303 ± 24 and 405 ± 46 days, respectively, for PSA Conclusions Use of NAAD in conjunction with IMRT leads to a significantly shortened time to normalization of serum PSA

  11. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

    Directory of Open Access Journals (Sweden)

    Paulo M F Cunha

    2010-07-01

    Full Text Available Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2 or the zinc-finger transcription factor lame duck (lmd lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  12. Modulation of Hematopoietic Lineage Specification Impacts TREM2 Expression in Microglia-Like Cells Derived From Human Stem Cells.

    Science.gov (United States)

    Amos, Peter J; Fung, Susan; Case, Amanda; Kifelew, Jerusalem; Osnis, Leah; Smith, Carole L; Green, Kevin; Naydenov, Alipi; Aloi, Macarena; Hubbard, Jesse J; Ramakrishnan, Aravind; Garden, Gwenn A; Jayadev, Suman

    2017-01-01

    Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines. Our approach is based on recent studies demonstrating that microglia originate from primitive yolk sac mesoderm distinct from peripheral macrophages that arise during definitive hematopoiesis. We hypothesized that functional microglia could be derived from human stem cells by employing BMP-4 mesodermal specification followed by exposure to microglia-relevant cytokines, M-CSF, GM-CSF, IL-34, and TGF-β. Using immunofluorescence microscopy, flow cytometry, and reverse transcription polymerase chain reaction, we observed cells with microglia morphology expressing a repertoire of markers associated with microglia: Iba1, CX3CR1, CD11b, TREM2, HexB, and P2RY12. These microglia-like cells maintain myeloid functional phenotypes including Aβ peptide phagocytosis and induction of pro-inflammatory gene expression in response to lipopolysaccharide stimulation. Addition of small molecules BIO and SB431542, previously demonstrated to drive definitive hematopoiesis, resulted in decreased surface expression of TREM2. Together, these data suggest that mesodermal lineage specification followed by cytokine exposure produces microglia-like cells in vitro from human pluripotent stem cells and that this phenotype can be modulated by factors influencing hematopoietic lineage in vitro.

  13. Shared Substance

    DEFF Research Database (Denmark)

    Gjerlufsen, Tony; Klokmose, Clemens Nylandsted; Eagan, James

    2011-01-01

    This paper presents a novel middleware for developing flexible interactive multi-surface applications. Using a scenario-based approach, we identify the requirements for this type of applications. We then introduce Substance, a data- oriented framework that decouples functionality from data, and S...

  14. Impacts of NMVOC emissions on human health in European countries for 2000-2010: Use of sector-specific substance profiles

    DEFF Research Database (Denmark)

    Laurent, Alexis; Hauschild, Michael Zwicky

    2014-01-01

    for 31 European countries within the period 2000e2010. Using life cycle impact assessment methods for POF and human toxicity, impacts on human health were quantified. The results indicated that a strong linear correlation exists between POF impacts and the total NMVOC emissions, suggesting that air...... assess the damages at national level and thus define adequate air pollution abatement policies, substance breakdowns are needed. However, these are not readily available as total NMVOC emissions are only reported at sector level. In this study, we developed a reproducible methodology that combines...... impacts (i) are caused by few substances, such as formaldehyde, acrolein and furan, (ii) primarily stem from transportation sectors and from residential sources, and (iii) are found not to correlate with total NMVOC emissions. Our findings therefore suggest the need for supporting air pollution abatement...

  15. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation

    NARCIS (Netherlands)

    Kamphuis, M.; Zwinderman, K.A.H.; Vogels, T.; Vliegen, H.W.; Kamphuis, R.P.; Ottenkamp, J.; Verloove-Vanhorick, S.P.; Bruil, J.

    2004-01-01

    This study represents the development and validation of a cardiac-specific module of the generic health-related quality of life (HRQoL) instrument, the TAAQOL (TNO/AZL Adult Quality Of Life), for young adults with congenital heart disease (CHD). Items were selected based on literature, an

  16. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri.

    Science.gov (United States)

    Hemarajata, P; Gao, C; Pflughoeft, K J; Thomas, C M; Saulnier, D M; Spinler, J K; Versalovic, J

    2013-12-01

    Human microbiome-derived strains of Lactobacillus reuteri potently suppress proinflammatory cytokines like human tumor necrosis factor (TNF) by converting the amino acid l-histidine to the biogenic amine histamine. Histamine suppresses mitogen-activated protein (MAP) kinase activation and cytokine production by signaling via histamine receptor type 2 (H2) on myeloid cells. Investigations of the gene expression profiles of immunomodulatory L. reuteri ATCC PTA 6475 highlighted numerous genes that were highly expressed during the stationary phase of growth, when TNF suppression is most potent. One such gene was found to be a regulator of genes involved in histidine-histamine metabolism by this probiotic species. During the course of these studies, this gene was renamed the Lactobacillus reuteri-specific immunoregulatory (rsiR) gene. The rsiR gene is essential for human TNF suppression by L. reuteri and expression of the histidine decarboxylase (hdc) gene cluster on the L. reuteri chromosome. Inactivation of rsiR resulted in diminished TNF suppression in vitro and reduced anti-inflammatory effects in vivo in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of acute colitis. A L. reuteri strain lacking an intact rsiR gene was unable to suppress colitis and resulted in greater concentrations of serum amyloid A (SAA) in the bloodstream of affected animals. The PhdcAB promoter region targeted by rsiR was defined by reporter gene experiments. These studies support the presence of a regulatory gene, rsiR, which modulates the expression of a gene cluster known to mediate immunoregulation by probiotics at the transcriptional level. These findings may point the way toward new strategies for controlling gene expression in probiotics by dietary interventions or microbiome manipulation.

  17. Normalization of prostate specific antigen in patients treated with intensity modulated radiotherapy for clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Schmitz, Matthew D; Padula, Gilbert DA; Chun, Patrick Y; Davis, Alan T

    2010-01-01

    The purpose of this study was to determine the expected time to prostate specific antigen (PSA) normalization with or without neoadjuvant androgen deprivation (NAAD) therapy after treatment with intensity modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer. A retrospective cohort research design was used. A total of 133 patients with clinical stage T1c to T3b prostate cancer (2002 AJCC staging) treated in a community setting between January 2002 and July 2005 were reviewed for time to PSA normalization using 1 ng/mL and 2 ng/mL as criteria. All patients received IMRT as part of their management. Times to PSA normalization were calculated using the Kaplan-Meier method. Significance was assessed at p < 0.05. Fifty-six of the 133 patients received NAAD (42.1%). Thirty-one patients (23.8%) received radiation to a limited pelvic field followed by an IMRT boost, while 99 patients received IMRT alone (76.2%). The times to serum PSA normalization < 2 ng/mL when treated with or without NAAD were 298 ± 24 and 302 ± 33 days (mean ± SEM), respectively (p > 0.05), and 303 ± 24 and 405 ± 46 days, respectively, for PSA < 1 ng/mL (p < 0.05). Stage T1 and T2 tumors had significantly increased time to PSA normalization < 1 ng/mL in comparison to Stage T3 tumors. Also, higher Gleason scores were significantly correlated with a faster time to PSA normalization < 1 ng/mL. Use of NAAD in conjunction with IMRT leads to a significantly shortened time to normalization of serum PSA < 1 ng/mL in patients with clinically localized prostate cancer

  18. Efficacy of an internet-based learning module and small-group debriefing on trainees' attitudes and communication skills toward patients with substance use disorders: results of a cluster randomized controlled trial.

    Science.gov (United States)

    Lanken, Paul N; Novack, Dennis H; Daetwyler, Christof; Gallop, Robert; Landis, J Richard; Lapin, Jennifer; Subramaniam, Geetha A; Schindler, Barbara A

    2015-03-01

    To examine whether an Internet-based learning module and small-group debriefing can improve medical trainees' attitudes and communication skills toward patients with substance use disorders (SUDs). In 2011-2012, 129 internal and family medicine residents and 370 medical students at two medical schools participated in a cluster randomized controlled trial, which assessed the effect of adding a two-part intervention to the SUDs curricula. The intervention included a self-directed, media-rich Internet-based learning module and a small-group, faculty-led debriefing. Primary study outcomes were changes in self-assessed attitudes in the intervention group (I-group) compared with those in the control group (C-group) (i.e., a difference of differences). For residents, the authors used real-time, Web-based interviews of standardized patients to assess changes in communication skills. Statistical analyses, conducted separately for residents and students, included hierarchical linear modeling, adjusted for site, participant type, cluster, and individual scores at baseline. The authors found no significant differences between the I- and C-groups in attitudes for residents or students at baseline. Compared with those in the C-group, residents, but not students, in the I-group had more positive attitudes toward treatment efficacy and self-efficacy at follow-up (Pcommunication skills toward patients with SUDs among residents. Enhanced attitudes and skills may result in improved care for these patients.

  19. Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs

    Energy Technology Data Exchange (ETDEWEB)

    Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerselvam, Lakshmikanthan; Perumal, Ekambaram, E-mail: ekas2009@buc.edu.in

    2017-02-15

    modulated by Fe{sub 2}O{sub 3}-NPs exposure • Male accessory organs specific markers expression were altered by Fe{sub 2}O{sub 3}-NPs • Histopathology revealed damage to both the accessory organs on Fe{sub 2}O{sub 3}-NPs exposure.

  20. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

    Directory of Open Access Journals (Sweden)

    Yunpeng Zhang

    2015-01-01

    Full Text Available Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM, to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

  1. Orientation-specific contextual modulation of the fMRI BOLD response to luminance and chromatic gratings in human visual cortex.

    Science.gov (United States)

    McDonald, J Scott; Seymour, Kiley J; Schira, Mark M; Spehar, Branka; Clifford, Colin W G

    2009-05-01

    The responses of orientation-selective neurons in primate visual cortex can be profoundly affected by the presence and orientation of stimuli falling outside the classical receptive field. Our perception of the orientation of a line or grating also depends upon the context in which it is presented. For example, the perceived orientation of a grating embedded in a surround tends to be repelled from the predominant orientation of the surround. Here, we used fMRI to investigate the basis of orientation-specific surround effects in five functionally-defined regions of visual cortex: V1, V2, V3, V3A/LO1 and hV4. Test stimuli were luminance-modulated and isoluminant gratings that produced responses similar in magnitude. Less BOLD activation was evident in response to gratings with parallel versus orthogonal surrounds across all the regions of visual cortex investigated. When an isoluminant test grating was surrounded by a luminance-modulated inducer, the degree of orientation-specific contextual modulation was no larger for extrastriate areas than for V1, suggesting that the observed effects might originate entirely in V1. However, more orientation-specific modulation was evident in extrastriate cortex when both test and inducer were luminance-modulated gratings than when the test was isoluminant; this difference was significant in area V3. We suggest that the pattern of results in extrastriate cortex may reflect a refinement of the orientation-selectivity of surround suppression specific to the colour of the surround or, alternatively, processes underlying the segmentation of test and inducer by spatial phase or orientation when no colour cue is available.

  2. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    Science.gov (United States)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  3. Substance abuse and cancer.

    Science.gov (United States)

    Moussas, G I; Papadopoulou, A G

    2017-01-01

    Substance abuse is a health problem with serious psychological and psychiatric dimensions and multiple social and economic consequences. Cancer is a disease that threatens not only life and physical integrity but mental health as well. Oncology patients suffer from mental disorders in high rates, especially from depression and anxiety. The role of substance abuse in the pathogenesis of cancer is studied systematically, since there are research data supporting the mutagenic effects of certain substances. It has been supported that a possible dysregulation of the immune system is linked to the oncogenic processes induced by substances of abuse. Specifically, opioids are the first addictive substances that have been identified as oncogenic factors. However, conflicting results have been offered by experimental animal studies, which showed that opioids, such as morphine, depending on the dosage administered, may not only enhance the process of tumor growth, but also inhibit it. Additionally, research data indicate that the use of cannabis may be associated with cancer, either as an independent factor or in relation to other mutagenics, although it is not yet clear to which extent these effects may be connected to the disease, especially once the consumption of tobacco and alcohol by these patients are taken into account. However, it has been argued that certain cannabinoids may have biological -anticancer- activities which could be used therapeutically without being accompanied by the corresponding 9-tetrahydrocannabinol psychoactive effects. It is well known that alcohol is a risk factor for developing head and neck cancer, and epidemiological studies indicate that the higher the consumption of alcohol, the more mortality due to cancer increases. In addition, it is suggested that there is no safety level for alcohol consumption regarding the risk of developing cancer; that is even a minimum daily consumption is associated with the occurrence of certain types of cancer

  4. Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

    Science.gov (United States)

    Trudell, James R.; Harris, R. Adron

    2014-01-01

    Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

  5. Development and first application of an Aerosol Collection Module (ACM) for quasi online compound specific aerosol measurements

    Science.gov (United States)

    Hohaus, Thorsten; Kiendler-Scharr, Astrid; Trimborn, Dagmar; Jayne, John; Wahner, Andreas; Worsnop, Doug

    2010-05-01

    Atmospheric aerosols influence climate and human health on regional and global scales (IPCC, 2007). In many environments organics are a major fraction of the aerosol influencing its properties. Due to the huge variety of organic compounds present in atmospheric aerosol current measurement techniques are far from providing a full speciation of organic aerosol (Hallquist et al., 2009). The development of new techniques for compound specific measurements with high time resolution is a timely issue in organic aerosol research. Here we present first laboratory characterisations of an aerosol collection module (ACM) which was developed to allow for the sampling and transfer of atmospheric PM1 aerosol. The system consists of an aerodynamic lens system focussing particles on a beam. This beam is directed to a 3.4 mm in diameter surface which is cooled to -30 °C with liquid nitrogen. After collection the aerosol sample can be evaporated from the surface by heating it to up to 270 °C. The sample is transferred through a 60cm long line with a carrier gas. In order to test the ACM for linearity and sensitivity we combined it with a GC-MS system. The tests were performed with octadecane aerosol. The octadecane mass as measured with the ACM-GC-MS was compared versus the mass as calculated from SMPS derived total volume. The data correlate well (R2 0.99, slope of linear fit 1.1) indicating 100 % collection efficiency. From 150 °C to 270 °C no effect of desorption temperature on transfer efficiency could be observed. The ACM-GC-MS system was proven to be linear over the mass range 2-100 ng and has a detection limit of ~ 2 ng. First experiments applying the ACM-GC-MS system were conducted at the Jülich Aerosol Chamber. Secondary organic aerosol (SOA) was formed from ozonolysis of 600 ppbv of b-pinene. The major oxidation product nopinone was detected in the aerosol and could be shown to decrease from 2 % of the total aerosol to 0.5 % of the aerosol over the 48 hours of

  6. PI3K/AKT signaling modulates transcriptional expression of EWS/FLI1 through specificity protein 1.

    Science.gov (United States)

    Giorgi, Chiara; Boro, Aleksandar; Rechfeld, Florian; Lopez-Garcia, Laura A; Gierisch, Maria E; Schäfer, Beat W; Niggli, Felix K

    2015-10-06

    Ewing sarcoma (ES) is the second most frequent bone cancer in childhood and is characterized by the presence of the balanced translocation t(11;22)(q24;q12) in more than 85% of cases, generating a dysregulated transcription factor EWS/FLI1. This fusion protein is an essential oncogenic component of ES development which is necessary for tumor cell maintenance and represents an attractive therapeutic target. To search for modulators of EWS/FLI1 activity we screened a library of 153 targeted compounds and identified inhibitors of the PI3K pathway to directly modulate EWS/FLI1 transcription. Surprisingly, treatment of four different ES cell lines with BEZ235 resulted in down regulation of EWS/FLI1 mRNA and protein by ~50% with subsequent modulation of target gene expression. Analysis of the EWS/FLI1 promoter region (-2239/+67) using various deletion constructs identified two 14 bp minimal elements as being important for EWS/FLI1 transcription. We identified SP1 as modulator of EWS/FLI1 gene expression and demonstrated direct binding to one of these regions in the EWS/FLI1 promoter by EMSA and ChIP experiments. These results provide the first insights on the transcriptional regulation of EWS/FLI1, an area that has not been investigated so far, and offer an additional molecular explanation for the known sensitivity of ES cell lines to PI3K inhibition.

  7. Specific characterization of non-steroidal selective androgen peceptor modulators using supercritical fluid chromatography coupled to ion-mobility mass spectrometry: application to the detection of enobosarm in bovine urine.

    Science.gov (United States)

    Beucher, Laure; Dervilly-Pinel, Gaud; Cesbron, Nora; Penot, Mylène; Gicquiau, Audrey; Monteau, Fabrice; Le Bizec, Bruno

    2017-02-01

    Currently under development for therapeutic purposes in human medicine, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth associated pathways. As such, they present a potential for abuse in sports and food-producing animals as interesting alternative anabolic substances. Forbidden since 2008 by the World Anti-Doping Agency (WADA) these compounds are however easily available and could be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies have to be developed for specific and sensitive detection of these compounds in biological matrices. Using an innovative analytical platform constituted of supercritical fluid chromatography coupled to ion mobility-mass spectrometry, the present study enabled efficient separation and identification in urine of 4 of these drugs (andarine, bicalutamide, hydroxyflutamide, and enobosarm) in accordance with European Union criteria (Commission Decision 2002/657/EC). Besides providing information about compounds structure and behaviour in gas phase, such a coupling enabled reaching low limits of detection (LOD < 0.05 ng.mL -1 for andarine and limits of detection < 0.005 ng.mL -1 for the three others) in urine with good repeatability (CV < 21 %). The workflow has been applied to quantitative determination of enobosarm elimination in urine of treated bovine (200 mg, oral). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Surround inhibition in the primary motor cortex is task-specifically modulated in non-professional musicians but not in healthy controls during real piano playing

    DEFF Research Database (Denmark)

    Márquez, Gonzalo; Keller, Martin; Lundbye-Jensen, Jesper

    2018-01-01

    participants. Transcranial magnetic stimulation (TMS) was applied to the contralateral motor cortex to assess SI in the first dorsal interosseous (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) during the movement preparation and the late phasic phases. The results reveal stronger SI...... that long-term training as observed in skilled musicians is accompanied by task-specific effects on SI modulation potentially relating to the ability to perform selective and complex finger movements....

  9. Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

    Science.gov (United States)

    Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

    2017-11-13

    The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly

  10. The Indirect Effect of Emotion Regulation on Minority Stress and Problematic Substance Use in Lesbian, Gay, and Bisexual Individuals

    Directory of Open Access Journals (Sweden)

    Andrew H. Rogers

    2017-10-01

    Full Text Available Lesbian, gay, and bisexual (LGB individuals report higher levels of problematic alcohol and substance use than their heterosexual peers. This disparity is linked to the experience of LGB-specific stressors, termed minority stress. Additionally, bisexual individuals show increased rates of psychopathology, including problematic alcohol and substance use, above and beyond lesbian and gay individuals. However, not everyone experiencing minority stress reports increased rates of alcohol and substance misuse. Emotion regulation (ER, which plays a critical role in psychopathology in general, is theorized to modulate the link between minority stress and psychopathology. However, it remains largely unknown whether ER plays a role in linking instances of minority stress with substance and alcohol use outcomes. To address the gap, the current study assessed 305 LGB individuals’ instances of minority stress, ER, and substance and alcohol use outcomes. We assessed the role of ER in problematic alcohol and substance use among LGB individuals using moderated mediation, where sexual minority status was entered as the moderator, and ER difficulties was entered as the mediator. The results indicated significant indirect effects of minority stress, through ER difficulties, on both problematic alcohol and substance use. However, there was no significant interaction with sexual orientation status, suggesting that ER may be important for all LGB individuals in predicting problematic alcohol and substance use. These results highlight the important role that ER plays between instances of minority stress and substance and alcohol use in LGB individuals, suggesting that ER skills may serve as a novel target for intervention.

  11. Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL.

    Science.gov (United States)

    Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

    2013-01-01

    Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions.

  12. Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL[S

    Science.gov (United States)

    Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

    2013-01-01

    Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions. PMID:23099443

  13. Tissue-specific expression of aryl hydrocarbon receptor and putative developmental regulatory modules in Baltic salmon yolk-sac fry

    Energy Technology Data Exchange (ETDEWEB)

    Vuori, Kristiina A. [Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku (Finland)], E-mail: kristiina.vuori@utu.fi; Nordlund, Eija [Department of Information Technology, University of Turku, and Turku Centre for Computer Science (TUCS), FI-20014 Turku (Finland); Kallio, Jenny [Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku (Finland); Salakoski, Tapio [Department of Information Technology, University of Turku, and Turku Centre for Computer Science (TUCS), FI-20014 Turku (Finland); Nikinmaa, Mikko [Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku (Finland)

    2008-04-08

    The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration. The mechanisms by which AhR regulates these various functions remain poorly understood. Across-species comparative studies of AhR in invertebrates, non-mammalian vertebrates and mammals may help to reveal the multiple functions of AhR. Here, we have studied AhR during larval development of Baltic salmon (Salmon salar). Our results indicate that AhR protein is expressed in nervous system, liver and muscle tissues. We also present putative regulatory modules and module-matching genes, produced by chromatin immunoprecipitation (ChIP) cloning and in silico analysis, which may be associated with evolutionarily conserved functions of AhR during development. For example, the module NFKB-AHRR-CREB found from salmon ChIP sequences is present in human ULK3 (regulating formation of granule cell axons in mouse and axon outgrowth in Caernohabditis elegans) and SRGAP1 (GTPase-activating protein involved in the Slit/Robo pathway) promoters. We suggest that AhR may have an evolutionarily conserved role in neuronal development and nerve cell targeting, and in Wnt signaling pathway.

  14. Tissue-specific expression of aryl hydrocarbon receptor and putative developmental regulatory modules in Baltic salmon yolk-sac fry

    International Nuclear Information System (INIS)

    Vuori, Kristiina A.; Nordlund, Eija; Kallio, Jenny; Salakoski, Tapio; Nikinmaa, Mikko

    2008-01-01

    The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration. The mechanisms by which AhR regulates these various functions remain poorly understood. Across-species comparative studies of AhR in invertebrates, non-mammalian vertebrates and mammals may help to reveal the multiple functions of AhR. Here, we have studied AhR during larval development of Baltic salmon (Salmon salar). Our results indicate that AhR protein is expressed in nervous system, liver and muscle tissues. We also present putative regulatory modules and module-matching genes, produced by chromatin immunoprecipitation (ChIP) cloning and in silico analysis, which may be associated with evolutionarily conserved functions of AhR during development. For example, the module NFKB-AHRR-CREB found from salmon ChIP sequences is present in human ULK3 (regulating formation of granule cell axons in mouse and axon outgrowth in Caernohabditis elegans) and SRGAP1 (GTPase-activating protein involved in the Slit/Robo pathway) promoters. We suggest that AhR may have an evolutionarily conserved role in neuronal development and nerve cell targeting, and in Wnt signaling pathway

  15. Site-specific protein O-glycosylation modulates proprotein processing - Deciphering specific functions of the large polypeptide GalNAc-transferase gene family

    DEFF Research Database (Denmark)

    Schjoldager, Katrine Ter-Borch Gram; Clausen, Henrik

    2012-01-01

    Posttranslational modifications (PTMs) greatly expand the function and regulation of proteins, and glycosylation is the most abundant and diverse PTM. Of the many different types of protein glycosylation, one is quite unique; GalNAc-type (or mucin-type) O-glycosylation, where biosynthesis...... and considerable redundancy. Recently we have begun to uncover human diseases associated with deficiencies in GalNAc-T genes (GALNTs). Thus deficiencies in individual GALNTs produce cell and protein specific effects and subtle distinct phenotypes such as hyperphosphatemia with hyperostosis (GALNT3...

  16. Substance Identification Information from EPA's Substance Registry

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Substance Registry Services (SRS) is the authoritative resource for basic information about substances of interest to the U.S. EPA and its state and tribal...

  17. Definition of Substance and Non-substance Addiction.

    Science.gov (United States)

    Zou, Zhiling; Wang, Huijun; d'Oleire Uquillas, Federico; Wang, Xiaomei; Ding, Jianrui; Chen, Hong

    2017-01-01

    Substance addiction (or drug addiction) is a neuropsychiatric disorder characterized by a recurring desire to continue taking the drug despite harmful consequences. Non-substance addiction (or behavioral addiction) covers pathological gambling, food addiction, internet addiction, and mobile phone addiction. Their definition is similar to drug addiction but they differ from each other in specific domains. This review aims to provide a brief overview of past and current definitions of substance and non-substance addiction, and also touches on the topic of diagnosing drug addiction and non-drug addiction, ultimately aiming to further the understanding of the key concepts needed for a foundation to study the biological and psychological underpinnings of addiction disorders.

  18. Quantitative determination of the specific heat and the glass transition of moist samples by temperature modulated differential scanning calorimetry.

    Science.gov (United States)

    Schubnell, M; Schawe, J E

    2001-04-17

    In differential scanning calorimetry (DSC), remnant moisture loss in samples often overlaps and distorts other thermal events, e.g. glass transitions. To separate such overlapping processes, temperature modulated DSC (TMDSC) has been widely used. In this contribution we discuss the quantitative determination of the heat capacity of a moist sample from TMDSC measurements. The sample was a spray-dried pharmaceutical compound run in different pans (hermetically-sealed pan, pierced lid pan [50 microm] and open pan). The apparent heat capacity was corrected for the remaining amount of moisture. Using this procedure we could clearly identify the glass transition of the dry and the moist sample. We found that a moisture content of about 6.2% shifts the glass transition by about 50 degrees C.

  19. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis.

    Science.gov (United States)

    Chen, Kang; Chen, Hao; Faas, Marijke M; de Haan, Bart J; Li, Jiahong; Xiao, Ping; Zhang, Hao; Diana, Julien; de Vos, Paul; Sun, Jia

    2017-08-01

    Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice. Female nonobese diabetic mice were weaned to long- and short-chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic-gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T-cell responses, as evidenced by increased CD25 + Foxp3 + CD4 + regulatory T cells, decreased IL17A + CD4 + Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase-1-p20-IL-1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide as well as short-chain fatty acid production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli. Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut-pancreatic immunity, barrier function, and microbiota homeostasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Osiris Marroquin Belaunzaran

    Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

  1. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats

    Science.gov (United States)

    Marroquin Belaunzaran, Osiris; Kleber, Sascha; Schauer, Stefan; Hausmann, Martin; Nicholls, Flora; Van den Broek, Maries; Payeli, Sravan; Ciurea, Adrian; Milling, Simon; Stenner, Frank; Shaw, Jackie; Kollnberger, Simon; Bowness, Paul; Petrausch, Ulf; Renner, Christoph

    2015-01-01

    Objectives HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders. Methods The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry. Results HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM). HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules. Conclusion HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders. PMID:26125554

  2. The specific features of self-action of high-power laser radiation propagating through a fully ionised cold plasma and the development of modulation instability

    International Nuclear Information System (INIS)

    Aleshkevich, Viktor A; Kartashev, Ya V; Vysloukh, Victor A

    2000-01-01

    The specific features of the propagation of soliton-like light beams through a fully ionised two-dimensional cold plasma are considered employing analytical and numerical methods commonly used in nonlinear optics. Exact soliton profiles for the lower and upper soliton branches are found numerically in the presence of optical bistability. It is shown that the interaction of incoherent soliton-like laser beams in such a plasma may result both in the destruction of one of the beams and in production of new ones. The regime of the modulation instability of a plane wave propagating through a cold laser-produced plasma is studied. (nonlinear optical phenomena)

  3. Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy

    Directory of Open Access Journals (Sweden)

    Kyung-Yil Lee

    2017-02-01

    Full Text Available Acute respiratory distress syndrome (ARDS is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis. The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.

  4. TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

    International Nuclear Information System (INIS)

    Brase, Jan C; Sirma, Hüseyin; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Beißbarth, Tim; Korf, Ulrike; Kuner, Ruprecht; Sültmann, Holger; Johannes, Marc; Mannsperger, Heiko; Fälth, Maria; Metzger, Jennifer; Kacprzyk, Lukasz A; Andrasiuk, Tatjana; Gade, Stephan; Meister, Michael

    2011-01-01

    TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear. We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays. Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors. The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy

  5. Conflict and disfluency as aversive signals: context-specific processing adjustments are modulated by affective location associations.

    Science.gov (United States)

    Dreisbach, Gesine; Reindl, Anna-Lena; Fischer, Rico

    2018-03-01

    Context-specific processing adjustments are one signature feature of flexible human action control. However, up to now the precise mechanisms underlying these adjustments are not fully understood. Here it is argued that aversive signals produced by conflict- or disfluency-experience originally motivate such context-specific processing adjustments. We tested whether the efficiency of the aversive conflict signal for control adaptation depends on the affective nature of the context it is presented in. In two experiments, high vs. low proportions of aversive signals (Experiment 1: conflict trials; Experiment 2: disfluent trials) were presented either above or below the screen center. This location manipulation was motivated by existing evidence that verticality is generally associated with affective valence with up being positive and down being negative. From there it was hypothesized that the aversive signals would lose their trigger function for processing adjustments when presented at the lower (i.e., more negative) location. This should then result in a reduced context-specific proportion effect when the high proportion of aversive signals was presented at the lower location. Results fully confirmed the predictions. In both experiments, the location-specific proportion effects were only present when the high proportion of aversive signals occurred at the more positive location above but were reduced (Experiment 1) or even eliminated (Experiment 2) when the high proportion occurred at the more negative location below. This interaction of processing adjustments with affective background contexts can thus be taken as further hint for an affective origin of control adaptations.

  6. Task-specific modulation of effective connectivity during two simple unimanual motor tasks: A 122-channel EEG study

    DEFF Research Database (Denmark)

    Herz, Damian M.; Christensen, Mark S.; Reck, Christiane

    2012-01-01

    Neural oscillations are thought to underlie coupling of spatially remote neurons and gating of information within the human sensorimotor system. Here we tested the hypothesis that different unimanual motor tasks are specifically associated with distinct patterns of oscillatory coupling in human...

  7. Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex

    Science.gov (United States)

    Joshi, Ankur; Kalappa, Bopanna I.; Anderson, Charles T.

    2016-01-01

    The neuromodulator acetylcholine (ACh) is crucial for several cognitive functions, such as perception, attention, and learning and memory. Whereas, in most cases, the cellular circuits or the specific neurons via which ACh exerts its cognitive effects remain unknown, it is known that auditory cortex (AC) neurons projecting from layer 5B (L5B) to the inferior colliculus, corticocollicular neurons, are required for cholinergic-mediated relearning of sound localization after occlusion of one ear. Therefore, elucidation of the effects of ACh on the excitability of corticocollicular neurons will bridge the cell-specific and cognitive properties of ACh. Because AC L5B contains another class of neurons that project to the contralateral cortex, corticocallosal neurons, to identify the cell-specific mechanisms that enable corticocollicular neurons to participate in sound localization relearning, we investigated the effects of ACh release on both L5B corticocallosal and corticocollicular neurons. Using in vitro electrophysiology and optogenetics in mouse brain slices, we found that ACh generated nicotinic ACh receptor (nAChR)-mediated depolarizing potentials and muscarinic ACh receptor (mAChR)-mediated hyperpolarizing potentials in AC L5B corticocallosal neurons. In corticocollicular neurons, ACh release also generated nAChR-mediated depolarizing potentials. However, in contrast to the mAChR-mediated hyperpolarizing potentials in corticocallosal neurons, ACh generated prolonged mAChR-mediated depolarizing potentials in corticocollicular neurons. These prolonged depolarizing potentials generated persistent firing in corticocollicular neurons, whereas corticocallosal neurons lacking mAChR-mediated depolarizing potentials did not show persistent firing. We propose that ACh-mediated persistent firing in corticocollicular neurons may represent a critical mechanism required for learning-induced plasticity in AC. SIGNIFICANCE STATEMENT Acetylcholine (ACh) is crucial for cognitive

  8. Subtype-specific Modulation of Acid-sensing Ion Channel (ASIC) Function by 2-Guanidine-4-methylquinazoline*

    Science.gov (United States)

    Alijevic, Omar; Kellenberger, Stephan

    2012-01-01

    Acid-sensing ion channels (ASICs) are neuronal Na+-selective channels that are transiently activated by extracellular acidification. ASICs are involved in fear and anxiety, learning, neurodegeneration after ischemic stroke, and pain sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently shown to open ASIC3 at physiological pH. We have investigated the mechanisms underlying this effect and the possibility that GMQ may alter the function of other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite direction and is accompanied by a decrease in its steepness. GMQ also induces an acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As a consequence, the activation and inactivation curves of ASIC3 but not other ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window current. At concentrations >1 mm, GMQ decreases maximal peak currents by reducing the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the GMQ effects on inactivation but not activation. This suggests that this residue is involved in the consequences of GMQ binding rather than in the binding interaction itself. This study describes the mechanisms underlying the effects of a novel class of ligands that modulate the function of all ASICs as well as activate ASIC3 at physiological pH. PMID:22948146

  9. Subtype-specific modulation of acid-sensing ion channel (ASIC) function by 2-guanidine-4-methylquinazoline.

    Science.gov (United States)

    Alijevic, Omar; Kellenberger, Stephan

    2012-10-19

    Acid-sensing ion channels (ASICs) are neuronal Na(+)-selective channels that are transiently activated by extracellular acidification. ASICs are involved in fear and anxiety, learning, neurodegeneration after ischemic stroke, and pain sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently shown to open ASIC3 at physiological pH. We have investigated the mechanisms underlying this effect and the possibility that GMQ may alter the function of other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite direction and is accompanied by a decrease in its steepness. GMQ also induces an acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As a consequence, the activation and inactivation curves of ASIC3 but not other ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window current. At concentrations >1 mM, GMQ decreases maximal peak currents by reducing the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the GMQ effects on inactivation but not activation. This suggests that this residue is involved in the consequences of GMQ binding rather than in the binding interaction itself. This study describes the mechanisms underlying the effects of a novel class of ligands that modulate the function of all ASICs as well as activate ASIC3 at physiological pH.

  10. The Verticillium-specific protein VdSCP7 localizes to the plant nucleus and modulates immunity to fungal infections.

    Science.gov (United States)

    Zhang, Lisha; Ni, Hao; Du, Xuan; Wang, Sheng; Ma, Xiao-Wei; Nürnberger, Thorsten; Guo, Hui-Shan; Hua, Chenlei

    2017-07-01

    Fungal pathogens secrete effector proteins to suppress plant basal defense for successful colonization. Resistant plants, however, can recognize effectors by cognate R proteins to induce effector-triggered immunity (ETI). By analyzing secretomes of the vascular fungal pathogen Verticillium dahliae, we identified a novel secreted protein VdSCP7 that targets the plant nucleus. The green fluorescent protein (GFP)-tagged VdSCP7 gene with either a mutated nuclear localization signal motif or with additional nuclear export signal was transiently expressed in Nicotiana benthamiana, and investigated for induction of plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized by gene knockout and complementation, and GFP labeling. Expression of the VdSCP7 gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and altered the plant's susceptibility to the pathogens Botrytis cinerea and Phytophthora capsici. The immune response activated by VdSCP7 was highly dependent on its initial extracellular secretion and subsequent nuclear localization in plants. Knockout of the VdSCP7 gene significantly enhanced V. dahliae aggressiveness on cotton. GFP-labeled VdSCP7 is secreted by V. dahliae and accumulates in the plant nucleus. We conclude that VdSCP7 is a novel effector protein that targets the host nucleus to modulate plant immunity, and suggest that plants can recognize VdSCP7 to activate ETI during fungal infection. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  11. IL-10 and NOS2 Modulate Antigen-Specific Reactivity and Nerve Infiltration by T Cells in Experimental Leprosy

    Science.gov (United States)

    Hagge, Deanna A.; Scollard, David M.; Ray, Nashone A.; Marks, Vilma T.; Deming, Angelina T.; Spencer, John S.; Adams, Linda B.

    2014-01-01

    Background Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions. Methodology/Principal Findings The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10−/−), as well as mice deficient in both inducible nitric oxide synthase (NOS2−/−) and IL-10 (10NOS2−/−). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B) were significantly increased in the evolved granuloma in NOS2−/− FP compared to B6 and IL-10−/− during early and peak phases. In 10NOS2−/− FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES), ML2038 (bacterioferritin), and ML1877 (EF-Tu). Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2−/− FP. Conclusions/Significance The 10NOS2−/− strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement. PMID:25210773

  12. Cell wall regeneration in Bangia atropurpurea (Rhodophyta) protoplasts observed using a mannan-specific carbohydrate-binding module.

    Science.gov (United States)

    Umemoto, Yoshiaki; Araki, Toshiyoshi

    2010-02-01

    The cell wall of the red alga Bangia atropurpurea is composed of three unique polysaccharides (beta-1,4-mannan, beta-1,3-xylan, and porphyran), similar to that in Porphyra. In this study, we visualized beta-mannan in the regenerating cell walls of B. atropurpurea protoplasts by using a fusion protein of a carbohydrate-binding module (CBM) and green fluorescent protein (GFP). A mannan-binding family 27 CBM (CBM27) of beta-1,4-mannanase (Man5C) from Vibrio sp. strain MA-138 was fused to GFP, and the resultant fusion protein (GFP-CBM27) was expressed in Escherichia coli. Native affinity gel electrophoresis revealed that GFP-CBM27 maintained its binding ability to soluble beta-mannans, while normal GFP could not bind to beta-mannans. Protoplasts were isolated from the fronds of B. atropurpurea by using three kinds of bacterial enzymes. The GFP-CBM27 was mixed with protoplasts from different growth stages, and the process of cell wall regeneration was observed by fluorescence microscopy. Some protoplasts began to excrete beta-mannan at certain areas of their cell surface after 12 h of culture. As the protoplast culture progressed, beta-mannans were spread on their entire cell surfaces. The percentages of protoplasts bound to GFP-CBM27 were 3%, 12%, 17%, 29%, and 25% after 12, 24, 36, 48, and 60 h of culture, respectively. Although GFP-CBM27 bound to cells at the initial growth stages, its binding to the mature fronds was not confirmed definitely. This is the first report on the visualization of beta-mannan in regenerating algal cell walls by using a fluorescence-labeled CBM.

  13. MicroRNA-29b modulates innate and antigen-specific immune responses in mouse models of autoimmunity.

    Directory of Open Access Journals (Sweden)

    Apolline Salama

    Full Text Available In addition to important regulatory roles in gene expression through RNA interference, it has recently been shown that microRNAs display immune stimulatory effects through direct interaction with receptors of innate immunity of the Toll-like receptor family, aggravating neuronal damage and tumour growth. Yet no evidence exists on consequences of microRNA immune stimulatory actions in the context of an autoimmune disease. Using microRNA analogues, we here show that pancreatic beta cell-derived microRNA sequences induce pro-inflammatory (TNFa, IFNa, IL-12, IL-6 or suppressive (IL-10 cytokine secretion by primary mouse dendritic cells in a sequence-dependent manner. For miR-29b, immune stimulation in RAW264.7 macrophages involved the endosomal Toll-like receptor-7, independently of the canonical RNA interference pathway. In vivo, the systemic delivery of miR-29b activates CD11b+B220- myeloid and CD11b-B220+ plasmacytoid dendritic cells and induces IFNa, TNFa and IL-6 production in the serum of recipient mice. Strikingly, in a murine model of adoptive transfer of autoimmune diabetes, miR-29b reduces the cytolytic activity of transferred effector CD8+ T-cells, insulitis and disease incidence in a single standalone intervention. Endogenous miR-29b, spontaneously released from beta-cells within exosomes, stimulates TNFa secretion from spleen cells isolated from diabetes-prone NOD mice in vitro. Hence, microRNA sequences modulate innate and ongoing adaptive immune responses raising the question of their potential role in the breakdown of tolerance and opening up new applications for microRNA-based immune therapy.

  14. Regulation of AKT phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner.

    Directory of Open Access Journals (Sweden)

    Hong Wa Yung

    2011-03-01

    Full Text Available Endoplasmic reticulum (ER stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473 confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308. The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling.

  15. Regulation of AKT Phosphorylation at Ser473 and Thr308 by Endoplasmic Reticulum Stress Modulates Substrate Specificity in a Severity Dependent Manner

    Science.gov (United States)

    Yung, Hong Wa

    2011-01-01

    Endoplasmic reticulum (ER) stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473) confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308). The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling. PMID:21445305

  16. A Systematic Study of Site-specific GalNAc-type O-Glycosylation Modulating Proprotein Convertase Processing

    DEFF Research Database (Denmark)

    Schjoldager, Katrine Ter-Borch Gram; Vester-Christensen, Malene B.; Goth, Christoffer K.

    2011-01-01

    Site-specific GalNAc-type O-glycosylation is emerging as an important co-regulator of proprotein convertase (PC) processing of proteins. PC processing is crucial in regulating many fundamental biological pathways and O-glycans in or immediately adjacent to processing sites may affect recognition...... and function of PCs. Thus, we previously demonstrated that deficiency in site-specific O-glycosylation in a PC site of the fibroblast growth factor, FGF23, resulted in marked reduction in secretion of active unprocessed FGF23, which cause familial tumoral calcinosis and hyperostosis hyperphosphatemia. GalNAc......-type O-glycosylation is found on serine and threonine amino acids and up to 20 distinct polypeptide GalNAc transferases catalyze the first addition of GalNAc to proteins making this step the most complex and differentially regulated steps in protein glycosylation. There is no reliable prediction model...

  17. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

    Science.gov (United States)

    Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

    2017-03-23

    Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

  18. IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy.

    Directory of Open Access Journals (Sweden)

    Deanna A Hagge

    2014-09-01

    Full Text Available Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions.The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-, as well as mice deficient in both inducible nitric oxide synthase (NOS2-/- and IL-10 (10NOS2-/-. Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP, inflammation increased from C57Bl/6 (B6modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement.

  19. Modulation of Bacillus thuringiensis Phosphatidylinositol-Specific Phospholipase C Activity by Mutations in the Putative Dimerization Interface

    Energy Technology Data Exchange (ETDEWEB)

    Shi, X.; Shao, C; Zhang, X; Zambonelli, C; Redfield, A; Head, J; Seaton, B; Roberts, M

    2009-01-01

    Cleavage of phosphatidylinositol (PI) to inositol 1,2-(cyclic)-phosphate (cIP) and cIP hydrolysis to inositol 1-phosphate by Bacillus thuringiensis phosphatidylinositol-specific phospholipase C are activated by the enzyme binding to phosphatidylcholine (PC) surfaces. Part of this reflects improved binding of the protein to interfaces. However, crystallographic analysis of an interfacially impaired phosphatidylinositol-specific phospholipase (W47A/W242A) suggested protein dimerization might occur on the membrane. In the W47A/W242A dimer, four tyrosine residues from one monomer interact with the same tyrosine cluster of the other, forming a tight dimer interface close to the membrane binding regions. We have constructed mutant proteins in which two or more of these tyrosine residues have been replaced with serine. Phospholipid binding and enzymatic activity of these mutants have been examined to assess the importance of these residues to enzyme function. Replacing two tyrosines had small effects on enzyme activity. However, removal of three or four tyrosine residues weakened PC binding and reduced PI cleavage by the enzyme as well as PC activation of cIP hydrolysis. Crystal structures of Y247S/Y251S in the absence and presence of myo-inositol as well as Y246S/Y247S/Y248S/Y251S indicate that both mutant proteins crystallized as monomers, were very similar to one another, and had no change in the active site region. Kinetic assays, lipid binding, and structural results indicate that either (i) a specific PC binding site, critical for vesicle activities and cIP activation, has been impaired, or (ii) the reduced dimerization potential for Y246S/Y247S/Y248S and Y246S/Y247S/Y248S/Y251S is responsible for their reduced catalytic activity in all assay systems.

  20. The composition and metabolism of faecal microbiota is specifically modulated by different dietary polysaccharides and mucin: an isothermal microcalorimetry study.

    Science.gov (United States)

    Adamberg, K; Kolk, K; Jaagura, M; Vilu, R; Adamberg, S

    2018-01-29

    The metabolic activity of colon microbiota is specifically affected by fibres with various monomer compositions, degree of polymerisation and branching. The supply of a variety of dietary fibres assures the diversity of gut microbial communities considered important for the well-being of the host. The aim of this study was to compare the impact of different oligo- and polysaccharides (galacto- and fructooligosaccharides, resistant starch, levan, inulin, arabinogalactan, xylan, pectin and chitin), and a glycoprotein mucin on the growth and metabolism of faecal microbiota in vitro by using isothermal microcalorimetry (IMC). Faecal samples from healthy donors were incubated in a phosphate-buffered defined medium with or without supplementation of a single substrate. The generation of heat was followed on-line, microbiota composition (V3-V4 region of the 16S rRNA using Illumina MiSeq v2) and concentrations of metabolites (HPLC) were determined at the end of growth. The multiauxic power-time curves obtained were substrate-specific. More than 70% of all substrates except chitin were fermented by faecal microbiota with total heat generation of up to 8 J/ml. The final metabolite patterns were in accordance with the microbiota changes. For arabinogalactan, xylan and levan, the fibre-affected distribution of bacterial taxa showed clear similarities (e.g. increase of Bacteroides ovatus and decrease of Bifidobacterium adolescentis). The formation of propionic acid, an important colon metabolite, was enhanced by arabinogalactan, xylan and mucin but not by galacto- and fructooligosaccharides or inulin. Mucin fermentation resulted in acetate, propionate and butyrate production in ratios previously observed for faecal samples, indicating that mucins may serve as major substrates for colon microbial population. IMC combined with analytical methods was shown to be an effective method for screening the impact of specific dietary fibres on functional changes in faecal microbiota.

  1. Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice.

    Science.gov (United States)

    Kozuka, Chisayo; Kaname, Tadashi; Shimizu-Okabe, Chigusa; Takayama, Chitoshi; Tsutsui, Masato; Matsushita, Masayuki; Abe, Keiko; Masuzaki, Hiroaki

    2017-08-01

    Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent γ-oryzanol attenuated the preference for an HFD via hypothalamic control. We therefore explored the possibility that γ-oryzanol would modulate functioning of the brain reward system in mice. Male C57BL/6J mice fed an HFD were orally treated with γ-oryzanol, and striatal levels of molecules involved in D2R signalling were evaluated. The impact of γ-oryzanol on DNA methylation of the D2R promoter and subsequent changes in preferences for dietary fat was examined. In addition, the effects of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methyltransferases (DNMTs), on food preference, D2R signalling and the levels of DNMTs in the striatum were investigated. The inhibitory effects of γ-oryzanol on the activity of DNMTs were enzymatically evaluated in vitro. In striatum from mice fed an HFD, the production of D2Rs was decreased via an increase in DNA methylation of the promoter region of the D2R. Oral administration of γ-oryzanol decreased the expression and activity of DNMTs, thereby restoring the level of D2Rs in the striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated the preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in the striatum of mice. Our experimental paradigm highlights

  2. O-GlcNAcylation modulates PKA-CREB signaling in a manner specific to PKA catalytic subunit isoforms.

    Science.gov (United States)

    Jin, Nana; Ma, Denglei; Gu, Jianlan; Shi, Jianhua; Xu, Xiaotao; Iqbal, Khalid; Gong, Cheng-Xin; Liu, Fei; Chu, Dandan

    2018-02-26

    O-GlcNAcylation is a post-translational modification of proteins. Protein kinase A (PKA)-cAMP response element binding protein (CREB) signaling plays critical roles in multiple biological processes. Isoforms α and β of PKA catalytic subunit (PKAc) and CREB are modified by O-GlcNAcylation. In the present study, we determined the role of O-GlcNAcylation in PKAc isoform-specific CREB signaling. We found that up-regulation of O-GlcNAcylation enhanced CREB phosphorylation, but suppressed CREB expression in exogenous PKAc isoform-unspecific manner. PKAc isoforms affected exogenous expression of OGT or OGA and protein O-GlcNAcylation differently. Up-regulation of O-GlcNAcylation did not significantly affect net PKAcα-CREB signaling, but enhanced PKAcβ-CREB signaling. The role of O-GlcNAcylation in PKA-CREB signaling was desensitized by insulin treatment. This study suggests a role of O-GlcNAcylation in PKA-CREB signaling by affecting phosphorylation of CREB in a PKAc isoform-specific manner. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Guri, Amir J; Noble, Alexis M; Reynolds, Kathryn A; King, Jennifer; Wood, Cynthia M; Ashby, Michael; Rai, Deshanie; Hontecillas, Raquel

    2007-03-01

    Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

  4. Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

    Science.gov (United States)

    Holland, Michelle L; Lowe, Robert; Caton, Paul W; Gemma, Carolina; Carbajosa, Guillermo; Danson, Amy F; Carpenter, Asha A M; Loche, Elena; Ozanne, Susan E; Rakyan, Vardhman K

    2016-07-29

    A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults. Copyright © 2016, American Association for the Advancement of Science.

  5. Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation

    International Nuclear Information System (INIS)

    Diermeier, Simone; Horvath, Gabor; Knuechel-Clarke, Ruth; Hofstaedter, Ferdinand; Szoellosi, Janos; Brockhoff, Gero

    2005-01-01

    Background: Growth factors and Herceptin specifically and differentially modulate cell proliferation of tumor cells. However, the mechanism of action on erbB-receptor level is incompletely understood. We evaluated Herceptin's capacity to modulate erbB-receptor activation and interaction on the cell surface level and thereby potentially impair cell proliferation of HER2/neu (c-erbB2) overexpressing breast cancer cells, both in the presence and absence of relevant growth factors. Methods: BT474 and SK-BR-3 breast cancer cell lines were treated with Epidermal Growth Factor (EGF), Heregulin, and with Herceptin in different combinations. Kinetics of cell proliferation were evaluated flow cytometrically based on BrdU-labeling. Fluorescence Resonance Energy Transfer, ELISAs and phosphorylation site specific Western Blotting was performed to investigate erbB-receptor interaction and activation. Results: EGF induced EGFR/EGFR and EGFR/c-erbB2 interactions correlate with stimulation of cell proliferation in BT474 cells. Both homo- and heterodimerization are considerably less pronounced in SK-BR-3 cells and heterointeraction is additionally reduced by EGF treatment, causing inhibition of cell proliferation. Heregulin stimulates cell proliferation extensively in both cell lines. Herceptin drives BT474 cells more efficiently into quiescence than it does with SK-BR-3 cells and thereby blocks cell cycle progress. In SK-BR-3 Herceptin treatment causes c-erbB2 phosphorylation of Y877 and Y1248, EGF induces Y877 and Y1112 phosphorylation. The Y1112 phosphorylation site, activated by EGF in SK-BR-3 cell, is bypassed in BT474. In addition the inhibitory capacity of Herceptin on BT474 and SK-BR-3 cell proliferation depends on the presence and absence of growth factors to a various extent. Conclusion: The growth inhibitory effect of Herceptin on c-erbB2 overexpressing breast cancer cells is considerably modulated by EGFR coexpression and consequently EGFR/c-erbB2 homo- and

  6. Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT genomic binding patterns discerns cell-specific cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Kang Keunsoo

    2013-01-01

    Full Text Available Abstract Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM, which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors.

  7. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

    2013-01-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

  8. Dosha phenotype specific Ayurveda intervention ameliorates asthma symptoms through cytokine modulations: Results of whole system clinical trial.

    Science.gov (United States)

    Joshi, Kalpana S; Nesari, Tanuja M; Dedge, Amrish P; Dhumal, Vikram R; Shengule, Sushant A; Gadgil, Maithili S; Salvi, Sundeep; Valiathan, Marthanda Varma Sankaran

    2017-02-02

    Over the past few decades, there have been significant scientific advances leading to improved understanding of asthma as a disease and treatment providing immediate relief. However, prevention of recurrent attacks, exacerbations and disease cure remains a challenge. Ayurveda refers to bronchial asthma as Tamaka Swasa and it is well explained in Charaka Samhita. Management of asthma in Ayurveda includes removal of vitiated Kapha through Shodhana, Shamana procedures, herbal and herbomineral formulations in addition to advising a healthy lifestyle and diet. Several clinical trials on Ayurvedic formulations for treatment of asthma are reported, however, whole system management of asthma has rarely been studied in the manner in which it is actually being practiced. Ayurveda therapeutics provides Dosha specific approaches, which needs biological investigation. The objective of our study was to investigate lung functions and cytokine changes in Asthmatic individuals in response to Ayurvedic intervention. The study design was approved by the Institutional Ethics Committee of Tilak Ayurveda Mahavidyalaya (TAMV) & Sheth Tarachand Ramnath Charitable Ayurveda Hospital and followed guidelines of the Declaration of Helsinki and Tokyo for humans. It was conducted as a whole system individualized pragmatic clinical trial and written consent of patients was collected before enrollment. One hundred and fifteen patients with mild-to-moderate asthma were divided into 2 sub-groups depending on their disease subsets and administered phenotype specific ayurvedic interventions. Seventy six asthma patients completed the treatment. Serum IgE levels, blood eosinophil counts, spirometry and blood cytokine levels were measured before the start of treatment and six months at the end of treatment. Age and sex matched healthy participants (n=69) were recruited in the study for comparison of cytokines levels. Significant improvements in FEV1(% predicted) (p<0.0001) and FVC (% predicted) (p=0

  9. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

    2013-06-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

  10. Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.

    Science.gov (United States)

    De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

    2013-01-01

    Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.

  11. D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice

    Directory of Open Access Journals (Sweden)

    Serena Boccella

    2015-01-01

    Full Text Available D-Aspartate (D-Asp is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO. D-Asp acts as an agonist on NMDA receptors (NMDARs. Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo−/− or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo−/− mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo−/− mice show an increased evoked activity of the nociceptive specific (NS neurons of the dorsal horn of the spinal cord (L4–L6 and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.

  12. Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs.

    Science.gov (United States)

    Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerselvam, Lakshmikanthan; Perumal, Ekambaram

    2017-02-15

    With increased industrial utilization of iron oxide nanoparticles (Fe 2 O 3 -NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe 2 O 3 -NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe 2 O 3 -NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe 2 O 3 -NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated iron levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe 2 O 3 -NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe 2 O 3 -NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe 2 O 3 -NPs could be an environmental risk factor for reproductive disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Early expression of pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice.

    Science.gov (United States)

    Blois, Sandra M; Tirado-González, Irene; Wu, Julie; Barrientos, Gabriela; Johnson, Briana; Warren, James; Freitag, Nancy; Klapp, Burghard F; Irmak, Ster; Ergun, Suleyman; Dveskler, Gabriela S

    2012-06-01

    Mouse and human pregnancy-specific glycoproteins (PSG) are known to exert immunomodulatory functions during pregnancy by inducing maternal leukocytes to secrete anti-inflammatory cytokines that promote a tolerogenic decidual microenvironment. Many such anti-inflammatory mediators also function as proangiogenic factors, which, along with the reported association of murine PSG with the uterine vasculature, suggest that PSG may contribute to the vascular adaptations necessary for successful implantation and placental development. We observed that PSG22 is strongly expressed around the embryonic crypt on Gestation Day 5.5, indicating that trophoblast giant cells are the main source of PSG22 during the early stages of pregnancy. PSG22 treatment up-regulated the secretion of transforming growth factor beta 1 and vascular endothelial growth factor A (VEGFA) in murine macrophages, uterine dendritic cells, and natural killer cells. A possible role of PSGs in uteroplacental angiogenesis is further supported by the finding that incubation of endothelial cells with PSG22 resulted in the formation of tubes in the presence and absence of VEGFA. We determined that PSG22, like human PSG1 and murine PSG17 and PSG23, binds to the heparan sulfate chains in syndecans. Therefore, our findings indicate that despite the independent evolution and expansion of human and rodent PSG, members in both families have conserved functions that include their ability to induce anti-inflammatory cytokines and proangiogenic factors as well as to induce the formation of capillary structures by endothelial cells. In summary, our results indicate that PSG22, the most abundant PSG expressed during mouse early pregnancy, is likely a major contributor to the establishment of a successful pregnancy.

  14. Supramodal Theta, Gamma, and Sustained Fields Predict Modality-specific Modulations of Alpha and Beta Oscillations during Visual and Tactile Working Memory.

    Science.gov (United States)

    van Ede, Freek; Jensen, Ole; Maris, Eric

    2017-08-01

    Flexible control over currently relevant sensory representations is an essential feature of primate cognition. We investigated the neurophysiological bases of such flexible control in humans during an intermodal working memory task in which participants retained visual or tactile sequences. Using magnetoencephalography, we first show that working memory retention engages early visual and somatosensory areas, as reflected in the sustained load-dependent suppression of alpha and beta oscillations. Next, we identify three components that are also load dependent but modality independent: medial prefrontal theta synchronization, frontoparietal gamma synchronization, and sustained parietal event-related fields. Critically, these domain-general components predict (across trials and within load conditions) the modality-specific suppression of alpha and beta oscillations, with largely unique contributions per component. Thus, working memory engages multiple complementary frontoparietal components that have discernible neuronal dynamics and that flexibly modulate retention-related activity in sensory areas in a manner that tracks the current contents of working memory.

  15. Pathway and Cell-Specific Kappa-Opioid Receptor Modulation of Excitatory-Inhibitory Balance Differentially Gates D1 and D2 Accumbens Neuron Activity

    Science.gov (United States)

    Tejeda, Hugo A.; Wu, Jocelyn; Kornspun, Alana R.; Pignatelli, Marco; Kashtelyan, Vadim; Krashes, Michael J.; Lowell, Brad B.; Carlezon, William A.; Bonci, Antonello

    2018-01-01

    Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases excitatory drive of D1 MSN activity by the amygdala, but not hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway specific manner. PMID:28056342

  16. Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance.

    Science.gov (United States)

    Muñoz-Martínez, Francisco; Lu, Peihua; Cortés-Selva, Fernando; Pérez-Victoria, José María; Jiménez, Ignacio A; Ravelo, Angel G; Sharom, Frances J; Gamarro, Francisco; Castanys, Santiago

    2004-10-01

    Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-beta-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential

  17. The adipokinetic hormone receptor modulates sexual behavior, pheromone perception and pheromone production in a sex-specific and starvation-dependent manner in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Sebastien eLebreton

    2016-01-01

    Full Text Available Food availability and nutritional status shape the reproductive activity of many animals. In rodents, hormones such as gonadotropin-releasing hormone (GnRH, restore energy homeostasis not only through regulating e.g. caloric intake and energy housekeeping, but also through modulating sex drive. We investigated whether the insect homologue of the GnRH receptor, the adipokinetic hormone receptor (AKHR modulates sexual behavior of the fruit fly Drosophila melanogaster depending on nutritional status. We found that AKHR regulates male, but not female sexual behavior in a starvation-dependent manner. Males lacking AKHR showed a severe decrease in their courtship activity when starved, as well as an increase in mating duration when fed. AKHR expression is particularly strong in the subesophageal zone (SEZ, Ito et al. 2014. We found axonal projections from AKHR-expressing neurons to higher brain centers including specific glomeruli in the antennal lobe. Among the glomeruli that received projections were those dedicated to detecting the male specific pheromone cis-vaccenyl acetate (cVA. Accordingly, responses to cVA were dependent on the nutritional status of flies. AKHR was also involved in the regulation of the production of cuticular pheromones, 7,11-heptacosadiene and 7-tricosene. This effect was observed only in females and depended on their feeding state. AKHR has therefore a dual role on both pheromone perception and production. For the first time our study shows an effect of AKHR on insect sexual behavior and physiology. Our results support the hypothesis of a conserved role of the GnRH/AKH pathway on a nutritional state-dependent regulation of reproduction in both vertebrates and invertebrates.

  18. Storage of hazardous substances in bonded warehouses

    International Nuclear Information System (INIS)

    Villalobos Artavia, Beatriz

    2008-01-01

    A variety of special regulations exist in Costa Rica for registration and transport of hazardous substances; these set the requirements for entry into the country and the security of transport units. However, the regulations mentioned no specific rules for storing hazardous substances. Tax deposits have been the initial place where are stored the substances that enter the country.The creation of basic rules that would be regulating the storage of hazardous substances has taken place through the analysis of regulations and national and international laws governing hazardous substances. The regulatory domain that currently exists will be established with a field research in fiscal deposits in the metropolitan area. The storage and security measures that have been used by the personnel handling the substances will be identified to be putting the reality with that the hazardous substances have been handled in tax deposits. A rule base for the storage of hazardous substances in tax deposits can be made, protecting the safety of the environment in which are manipulated and avoiding a possible accident causing a mess around. The rule will have the characteristics of the storage warehouses hazardous substances, such as safety standards, labeling standards, infrastructure features, common storage and transitional measures that must possess and meet all bonded warehouses to store hazardous substances. (author) [es

  19. TSCA Chemical Substance Inventory

    Science.gov (United States)

    Section 8 (b) of the Toxic Substances Control Act (TSCA) requires EPA to compile, keep current, and publish a list of each chemical substance that is manufactured or processed in the United States for TSCA uses.

  20. Documentation of the dynamic parameter, water-use, stream and lake flow routing, and two summary output modules and updates to surface-depression storage simulation and initial conditions specification options with the Precipitation-Runoff Modeling System (PRMS)

    Science.gov (United States)

    Regan, R. Steve; LaFontaine, Jacob H.

    2017-10-05

    This report documents seven enhancements to the U.S. Geological Survey (USGS) Precipitation-Runoff Modeling System (PRMS) hydrologic simulation code: two time-series input options, two new output options, and three updates of existing capabilities. The enhancements are (1) new dynamic parameter module, (2) new water-use module, (3) new Hydrologic Response Unit (HRU) summary output module, (4) new basin variables summary output module, (5) new stream and lake flow routing module, (6) update to surface-depression storage and flow simulation, and (7) update to the initial-conditions specification. This report relies heavily upon U.S. Geological Survey Techniques and Methods, book 6, chapter B7, which documents PRMS version 4 (PRMS-IV). A brief description of PRMS is included in this report.

  1. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

    Science.gov (United States)

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    pools of neurons that may modulate specific cortical areas.

  2. Relationships as determinants of substance use amongst street ...

    African Journals Online (AJOL)

    Background: Unrestrained exposure to street life often makes the street child vulnerable to psychoactive substances. In other settings, the social relationships of the substance user with those around him or her and family norms of parenting have been docu-mented to modulate use. However, there is a dearth of literature on ...

  3. Modulational effects in accelerators

    International Nuclear Information System (INIS)

    Satogata, T.

    1997-01-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

  4. A platform to screen for C-type lectin receptor-binding carbohydrates and their potential for cell-specific targeting and immune modulation.

    Science.gov (United States)

    Maglinao, Maha; Eriksson, Magdalena; Schlegel, Mark K; Zimmermann, Stephanie; Johannssen, Timo; Götze, Sebastian; Seeberger, Peter H; Lepenies, Bernd

    2014-02-10

    Myeloid C-type lectin receptors (CLRs) in innate immunity represent a superfamily of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-antigens. The primary interaction of an antigen-presenting cell and a pathogen shapes the following immune response. Therefore, the identification of CLR ligands that can either enhance or modulate the immune response is of interest. We have developed a screening platform based on glycan arrays to identify immune modulatory carbohydrate ligands of CLRs. A comprehensive library of CLRs was expressed by fusing the extracellular part of each respective CLR, the part containing the carbohydrate-recognition domain (CRD), to the Fc fragment of human IgG1 molecules. CLR-Fc fusion proteins display the CRD in a dimeric form, are properly glycosylated, and can be detected by a secondary antibody with a conjugated fluorophore. Thus, they are valuable tools for high-throughput screening. We were able to identify novel carbohydrate binders of CLRs using the glycan array technology. These CLR-binding carbohydrates were then covalently attached to the model antigen ovalbumin. The ovalbumin neoglycoconjugates were used in a dendritic cell/T cell co-culture assay to stimulate transgenic T cells in vitro. In addition, mice were immunized with these conjugates to analyze the immune modulatory properties of the CLR ligands in vivo. The CLR ligands induced an increased Th1 cytokine production in vitro and modulated the humoral response in vivo. The platform described here allows for the identification of CLR ligands, as well as the evaluation of each ligand's cell-specific targeting and immune modulatory properties. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. AtSOFL1 and AtSOFL2 act redundantly as positive modulators of the endogenous content of specific cytokinins in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Jingyu Zhang

    Full Text Available BACKGROUND: Although cytokinins have been known for decades to play important roles in the regulation of plant growth and development, our knowledge of the regulatory mechanism of endogenous content of specific cytokinins remains limited. METHODOLOGY/PRINCIPAL FINDINGS: Here, we characterized two SOB five-like (SOFL genes, AtSOFL1 and AtSOFL2, in Arabidopsis (Arabidopsis thaliana and showed that they acted redundantly in regulating specific cytokinin levels. Analysis of the translational fusion AtSOFL1:AtSOFL1-GUS and AtSOFL2:AtSOFL2-GUS indicated that AtSOFL1 and AtSOFL2 exhibited similar expression patterns. Both proteins were predominantly expressed in the vascular tissues of developing leaves, flowers and siliques, but barely detectable in roots and stems. Overexpression of either AtSOFL1 or AtSOFL2 led to increased cytokinin content and obvious corresponding mutant phenotypes for both transgenic seedlings and adult plants. In addition, overexpression and site-directed mutagenesis experiments demonstrated that the SOFL domains are necessary for AtSOFL2's overexpression phenotypes. Silencing or disrupting either AtSOFL1 or AtSOFL2 caused no obvious developmental defects. Endogenous cytokinin analysis, however, revealed that compared to the wild type control, the SOFL1-RNAi62 sofl2-1 double mutant accumulated lower levels of trans-zeatin riboside monophosphate (tZRMP and N(6-(Delta(2-isopentenyladenosine monophosphate (iPRMP, which are biosynthetic intermediates of bioactive cytokinins. The double mutant also displayed decreased response to exogenous cytokinin in both callus-formation and inhibition-of-hypocotyl-elongation assays. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that in plants AtSOFL1 and AtSOFL2 work redundantly as positive modulators in the fine-tuning of specific cytokinin levels as well as responsiveness.

  6. Former substance users working as counselors

    DEFF Research Database (Denmark)

    Hecksher, Dorte

    2007-01-01

    All helping professionals risk participation in "dual relationships". But in the case of former substance users working as counselors, specific dilemmas and problems are accentuated. A qualitative analysis highlights some of the ethical and personal dilemmas faced by these counselors. The data...... is derived from an interview study initiated in 2000 in Denmark on former substance users with 4 -8 years of abstinence. Through an analysis of interview data from a larger group of former substance users, it became evident that those working as counselors experienced specific dilemmas and problems...

  7. WE-DE-207B-11: Implementation of Size-Specific 3D Beam Modulation Filters On a Dedicated Breast CT Platform Using Breast Immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, A [Department of Radiology, Biomedical Engineering Graduate Group, University of California Davis, Sacramento, CA (United States); Boone, J [Departments of Radiology and Biomedical Engineering, University of California Davis, Sacramento, CA (United States)

    2016-06-15

    Purpose: To implement a 3D beam modulation filter (3D-BMF) in dedicated breast CT (bCT) and develop a method for conforming the patient’s breast to a pre-defined shape, optimizing the effects of the filter. This work expands on previous work reporting the methodology for designing a 3D-BMF that can spare unnecessary dose and improve signal equalization at the detector by preferentially filtering the beam in the thinner anterior and peripheral breast regions. Methods: Effective diameter profiles were measured for 219 segmented bCT images, grouped into volume quintiles, and averaged within each group to represent the range of breast sizes found clinically. These profiles were then used to generate five size-specific computational phantoms and fabricate five size-specific UHMW phantoms. Each computational phantom was utilized for designing a size-specific 3D-BMF using previously reported methods. Glandular dose values and projection images were simulated in MCNP6 with and without the 3DBMF using the system specifications of our prototype bCT scanner “Doheny”. Lastly, thermoplastic was molded around each of the five phantom sizes and used to produce a series of breast immobilizers for use in conforming the patient’s breast during bCT acquisition. Results: After incorporating the 3D-BMF, MC simulations estimated an 80% average reduction in the detector dynamic range requirements across all phantom sizes. The glandular dose was reduced on average 57% after normalizing by the number of quanta reaching the detector under the thickest region of the breast. Conclusion: A series of bCT-derived breast phantoms were used to design size-specific 3D-BMFs and breast immobilizers that can be used on the bCT platform to conform the patient’s breast and therefore optimally exploit the benefits of the 3D-BMF. Current efforts are focused on fabricating several prototype 3D-BMFs and performing phantom scans on Doheny for MC simulation validation and image quality analysis

  8. WE-DE-207B-11: Implementation of Size-Specific 3D Beam Modulation Filters On a Dedicated Breast CT Platform Using Breast Immobilization

    International Nuclear Information System (INIS)

    Hernandez, A; Boone, J

    2016-01-01

    Purpose: To implement a 3D beam modulation filter (3D-BMF) in dedicated breast CT (bCT) and develop a method for conforming the patient’s breast to a pre-defined shape, optimizing the effects of the filter. This work expands on previous work reporting the methodology for designing a 3D-BMF that can spare unnecessary dose and improve signal equalization at the detector by preferentially filtering the beam in the thinner anterior and peripheral breast regions. Methods: Effective diameter profiles were measured for 219 segmented bCT images, grouped into volume quintiles, and averaged within each group to represent the range of breast sizes found clinically. These profiles were then used to generate five size-specific computational phantoms and fabricate five size-specific UHMW phantoms. Each computational phantom was utilized for designing a size-specific 3D-BMF using previously reported methods. Glandular dose values and projection images were simulated in MCNP6 with and without the 3DBMF using the system specifications of our prototype bCT scanner “Doheny”. Lastly, thermoplastic was molded around each of the five phantom sizes and used to produce a series of breast immobilizers for use in conforming the patient’s breast during bCT acquisition. Results: After incorporating the 3D-BMF, MC simulations estimated an 80% average reduction in the detector dynamic range requirements across all phantom sizes. The glandular dose was reduced on average 57% after normalizing by the number of quanta reaching the detector under the thickest region of the breast. Conclusion: A series of bCT-derived breast phantoms were used to design size-specific 3D-BMFs and breast immobilizers that can be used on the bCT platform to conform the patient’s breast and therefore optimally exploit the benefits of the 3D-BMF. Current efforts are focused on fabricating several prototype 3D-BMFs and performing phantom scans on Doheny for MC simulation validation and image quality analysis

  9. Adolescent Sexual Behaviors at Varying Levels of Substance Use Frequency

    Science.gov (United States)

    Floyd, Leah J.; Latimer, William

    2010-01-01

    Combining substance use and sex compounds the risk of contracting sexually transmitted diseases, including HIV. However, the association between substance use and sexual behaviors may vary by substance and sexual behavior. The current study sought to examine the relationship between alcohol and marijuana use frequency and specific sexual…

  10. A substrate specificity-determining unit of three Lin12-Notch repeat modules is formed in trans within the pappalysin-1 dimer and requires a sequence stretch C-terminal to the third module

    DEFF Research Database (Denmark)

    Weyer, Kathrin; Boldt, Henning B; Poulsen, Christine B

    2007-01-01

    -A cleaves IGFBP-4 and IGFBP-5, whereas PAPP-A2 cleaves only IGFBP-5. The pappalysins contain three Lin12-Notch repeat (LNR1-3) modules, previously considered unique to the Notch receptor family in which they function to regulate receptor cleavage. In contrast to the Notch receptor where three LNR modules...

  11. The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity.

    Science.gov (United States)

    Vanli, Güliz; Peltzer, Nieves; Dubuis, Gilles; Widmann, Christian

    2014-12-01

    The caspase-3/p120 RasGAP module acts as a stress sensor that promotes pro-survival or pro-death signaling depending on the intensity and the duration of the stressful stimuli. Partial cleavage of p120 RasGAP generates a fragment, called fragment N, which protects stressed cells by activating Akt signaling. Akt family members regulate many cellular processes including proliferation, inhibition of apoptosis and metabolism. These cellular processes are regulated by three distinct Akt isoforms: Akt1, Akt2 and Akt3. However, which of these isoforms are required for fragment N mediated protection have not been defined. In this study, we investigated the individual contribution of each isoform in fragment N-mediated cell protection against Fas ligand induced cell death. To this end, DLD1 and HCT116 isogenic cell lines lacking specific Akt isoforms were used. It was found that fragment N could activate Akt1 and Akt2 but that only the former could mediate the protective activity of the RasGAP-derived fragment. Even overexpression of Akt2 or Akt3 could not rescue the inability of fragment N to protect cells lacking Akt1. These results demonstrate a strict Akt isoform requirement for the anti-apoptotic activity of fragment N. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Long-term disease-specific and cognitive quality of life after intensity-modulated radiation therapy: a cross-sectional survey of nasopharyngeal carcinoma survivors

    International Nuclear Information System (INIS)

    Kiang, Alan; Weinberg, Vivian K.; Cheung, Ka Ho Nicholas; Shugard, Erin; Chen, Josephine; Quivey, Jeanne M.; Yom, Sue S.

    2016-01-01

    There is a lack of data on quality of life in long-term survivors of nasopharyngeal carcinoma (NPC) who have been treated with intensity-modulated radiation therapy (IMRT). We characterized long-term disease-specific and cognitive QoL in NPC survivors after IMRT. We conducted a cross-sectional study of surviving patients diagnosed and treated for NPC at our center with curative-intent IMRT, with or without chemotherapy. Patients who were deceased, still undergoing treatment, with known recurrent disease, or treated with RT modality other than IMRT were excluded. QoL was measured by FACT-NP and FACT-Cog. Between May and November 2013, 44 patients completed cognitive (FACT-Cog), general (FACT-G), and NPC-specific (NPCS) QoL assessments. Patients were categorized into 4 cohorts based on duration since IMRT (≤2.5, >2.5–6, >6–10, and >10–16 years). There was no significant difference in age (p = 0.20) or stage ((I/II vs III/IV: p = 0.78) among the cohorts. The 4 cohorts differed overall for all QoL measures (ANOVA: p < 0.02 for each), due to improved scores >2.5–6 years post-IMRT compared with ≤2.5 years post-IMRT (post hoc tests: p ≤ 0.04 for each). No differences were observed between >2.5–6 and >6–10 years post-IMRT, but lower mean FACT-Cog and NPCS scores were observed for >10 years compared to >2.5–6 years post-IMRT (post hoc: p < 0.05 for each). All QoL measures were low during the initial recovery period (≤2.5 years) and were higher by 6 years post-IMRT. At >10 years post-IMRT, lower scores were observed in the domains of NPC-specific and cognitive QoL. Survivors of NPC, even if treated with IMRT, are at risk for detriment in domain-specific QoL measures at very long-term follow-up

  13. Conserved regulatory modules in the Sox9 testis-specific enhancer predict roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination.

    Science.gov (United States)

    Bagheri-Fam, Stefan; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

    2010-03-01

    While the primary sex determining switch varies between vertebrate species, a key downstream event in testicular development, namely the male-specific up-regulation of Sox9, is conserved. To date, only two sex determining switch genes have been identified, Sry in mammals and the Dmrt1-related gene Dmy (Dmrt1bY) in the medaka fish Oryzias latipes. In mice, Sox9 expression is evidently up-regulated by SRY and maintained by SOX9 both of which directly activate the core 1.3 kb testis-specific enhancer of Sox9 (TESCO). How Sox9 expression is up-regulated and maintained in species without Sry (i.e. non-mammalian species) is not understood. In this study, we have undertaken an in-depth comparative genomics approach and show that TESCO contains an evolutionarily conserved region (ECR) of 180 bp which is present in marsupials, monotremes, birds, reptiles and amphibians. The ECR contains highly conserved modules that predict regulatory roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination/differentiation. Our data suggest that tetrapods share common aspects of Sox9 regulation in the testis, despite having different sex determining switch mechanisms. They also suggest that Sox9 autoregulation is an ancient mechanism shared by all tetrapods, raising the possibility that in mammals, SRY evolved by mimicking this regulation. The validation of ECR regulatory sequences conserved from human to frogs will provide new insights into vertebrate sex determination. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. NF-Y recruits both transcription activator and repressor to modulate tissue- and developmental stage-specific expression of human γ-globin gene.

    Directory of Open Access Journals (Sweden)

    Xingguo Zhu

    Full Text Available The human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal γ-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal γ-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal γ-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed γ-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of γ-globin gene.

  15. Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.

    Science.gov (United States)

    Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K

    2014-05-01

    Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Pierre Raeven

    Full Text Available INTRODUCTION: Plasminogen activator inhibitor 1 (PAI-1 is a key factor in trauma- and sepsis-induced coagulopathy. We examined how trauma-hemorrhage (TH modulates PAI-1 responses in subsequent cecal ligation and puncture (CLP-induced sepsis, and the association of PAI-1 with septic outcomes. METHODS: Mice underwent TH and CLP 48 h later in three separate experiments. In experiment 1, mice were sacrificed pre- and post-CLP to characterize the trajectory of PAI-1 in plasma (protein and tissues (mRNA. Post-CLP dynamics in TH-CLP (this study and CLP-Only mice (prior study were then compared for modulatory effects of TH. In experiment 2, to relate PAI-1 changes to outcome, mice underwent TH-CLP and were sampled daily and followed for 14 days to compare non-survivors (DEAD and survivors (SUR. In experiment 3, plasma and tissue PAI-1 expression were compared between mice predicted to die (P-DIE and to live (P-LIVE. RESULTS: In experiment 1, an early post-TH rise of circulating PAI-1 was contrasted by a delayed (post-TH decrease of PAI-1 mRNA in organs. In the post-CLP phase, profiles of circulating PAI-1 were similar between TH-CLP and CLP-Only mice. Conversely, PAI-1 mRNA declined in the liver and heart of TH-CLP mice versus CLP-Only. In experiment 2, there were no DEAD/SUR differences in circulating PAI-1 prior to CLP. Post-CLP, circulating PAI-1 in DEAD was 2-4-fold higher than in SUR. PAI-1 increase heralded septic deaths up to 48 h prior but DEAD/SUR thrombomodulin (endothelial injury marker levels were identical. In experiment 3, levels of circulating PAI-1 and its hepatic gene expression were higher in P-DIE versus P-LIVE mice and those increases closely correlated with liver dysfunction. CONCLUSIONS: Trauma modulated septic PAI-1 responses in a compartment-specific fashion. Only post-CLP increases in circulating PAI-1 predicted septic outcomes. In posttraumatic sepsis, pre-lethal release of PAI-1 was mostly of hepatic origin and was independent

  17. Substance use - cocaine

    Science.gov (United States)

    Substance abuse - cocaine; Drug abuse - cocaine; Drug use - cocaine ... thinking clearly Mood and emotional problems, such as aggressive or violent behavior Restlessness and tremors Sleep problems ...

  18. Substance use - phencyclidine (PCP)

    Science.gov (United States)

    PCP; Substance abuse - phencyclidine; Drug abuse - phencyclidine; Drug use - phencyclidine ... a result, you may act strangely or become aggressive and violent. PCP's other harmful effects include: It ...

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

    Science.gov (United States)

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

    2016-04-01

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

  20. The construction and testing of the EORTC colorectal cancer-specific quality of life questionnaire module (QLQ-CR38). European Organization for Research and Treatment of Cancer Study Group on Quality of Life

    NARCIS (Netherlands)

    Sprangers, M. A.; te Velde, A.; Aaronson, N. K.

    1999-01-01

    The objectives of the current study were to construct a colorectal cancer-specific quality of life (QL) questionnaire module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity in The Netherlands.

  1. Human muscle-specific A-kinase anchoring protein (mAKAP) polymorphisms modulate the susceptibility to cardiovascular diseases by altering cAMP/ PKA signaling.

    Science.gov (United States)

    Suryavanshi, Santosh V; Jadhav, Shweta M; Anderson, Kody L; Katsonis, Panagiotis; Lichtarge, Olivier; McConnell, Bradley K

    2018-03-30

    One of the crucial cardiac signaling pathways is cAMP-mediated PKA signal transduction which is regulated by a family of scaffolding proteins, A-kinase anchoring proteins (AKAPs). Muscle-specific AKAP (mAKAP) partly regulates cardiac cAMP/PKA signaling by binding to PKA and phosphodiesterase4D3 (PDE4D3) among other proteins and plays a central role in modulating cardiac remodeling. Moreover, genetics plays an incomparable role in modifying the risk of cardiovascular diseases (CVDs). Especially, single nucleotide polymorphisms (SNPs) in various proteins have been shown to predispose individuals to CVDs. Hence, we hypothesized that human mAKAP polymorphisms found in humans with CVDs alter cAMP/PKA pathway influencing the susceptibility of individuals to CVDs. Our computational analyses revealed two mAKAP SNPs found in cardiac disease related patients with highest predicted deleterious effects, Ser(S) 1653 Arg(R) and Glu(E) 2124 Gly(G). Co-immunoprecipitation data in HEK293T cells showed that S1653R SNP, present in the PDE4D3 binding domain of mAKAP, changed the binding of PDE4D3 to mAKAP and E2124G SNP, flanking the 3'-PKA binding domain, changed the binding of PKA before and after stimulation with isoproterenol. These SNPs significantly altered intracellular cAMP levels, global PKA activity and cytosolic PDE activity when compared with the wild-type (WT) before and after isoproterenol stimulation. PKA-mediated phosphorylation of pathological markers was found to be up-regulated after cell stimulation in both mutants. In conclusion, human mAKAP polymorphisms may influence the propensity of developing CVDs by affecting cAMP/PKA signaling supporting the clinical significance of PKA-mAKAP-PDE4D3 interactions.

  2. Pharmacological modulation of mGluR7 with AMN082 and MMPIP exerts specific influences on alcohol consumption and preference in rats.

    Science.gov (United States)

    Bahi, Amine; Fizia, Katharina; Dietz, Monika; Gasparini, Fabrizio; Flor, Peter J

    2012-03-01

    Growing evidence supports a role for the central nervous system (CNS) neurotransmitter L-glutamate and its metabotropic receptors (mGluRs) in drug addiction in general and alcohol-use disorders in particular. Alcohol dependence, for instance, has a genetic component, and the recent discovery that variations in the gene coding for mGluR7 modulate alcohol consumption further validates involvement of the L-glutamate system. Consequently, increasing interest emerges in developing L-glutamatergic therapies for the treatment of alcohol abuse and dependence. To this end, we performed a detailed behavioral pharmacology study to investigate the regulation of alcohol consumption and preference following administration of the mGluR7-selective drugs N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082) and 6-(4-Methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP). Upon administration of the allosteric agonist AMN082 (10 mg/kg, i.p.) in rats, there was a significant decrease in ethanol consumption and preference, without affecting ethanol blood metabolism. In contrast, mGluR7 blockade with MMPIP (10 mg/kg, i.p.) showed an increase in alcohol intake and reversed AMN082's effect on ethanol consumption and preference. Both mGluR7-directed pharmacological tools had no effect on total fluid intake, taste preference, or on spontaneous locomotor activity. In conclusion, these findings support a specific regulatory role for mGluR7 on alcohol drinking and preference and provide evidence for the use of AMN082-type drugs as potential new treatments for alcohol-use disorders in man. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  3. Radioactive Substances Act 1948

    International Nuclear Information System (INIS)

    1948-01-01

    This Act regulates the use of radioactive substances and radiation producing devices in the United Kingdom. It provides for the control of import, export, sale, supply etc. of such substances and devices and lays down the safety regulations to be complied with when dealing with them. (NEA) [fr

  4. Transport of radioactive substances

    International Nuclear Information System (INIS)

    2014-12-01

    The report on the transport of radioactive substances covers the following topics: facts on radioactive materials transport, safety of the transport of radioactive substances, legal regulations and guidelines: a multiform but consistent system, transport of nuclear fuels, safety during the transport of nuclear fuel, future transport of spent fuel elements and high-level radioactive wastes in Germany.

  5. Patient-specific quality assurance for the delivery of 60Co intensity modulated radiation therapy subject to a 0.35 T lateral magnetic field

    Science.gov (United States)

    Li, H. Harold; Rodriguez, Vivian L.; Green, Olga L.; Hu, Yanle; Kashani, Rojano; Wooten, H. Omar; Yang, Deshan; Mutic, Sasa

    2014-01-01

    Purpose This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging guided radiation therapy device. Methods and materials The program consisted of the following components: 1) one-dimensional multipoint ionization chamber measurement using a customized 15 cm3 cubic phantom, 2) two-dimensional (2D) radiographic film measurement using a 30×30×20 cm3 phantom with multiple inserted ionization chambers, 3) quasi- three-dimensional (3D) diode array (ArcCHECK) measurement with a centrally inserted ionization chamber, 4) 2D fluence verification using machine delivery log files, and 5) 3D Monte-Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Results The ionization chamber measurements agreed well with treatment planning system (TPS) computed doses in all phantom geometries where the mean difference (mean ± SD) was 0.0% ± 1.3% (n=102, range, −3.0 % to 2.9%). The film measurements also showed excellent agreement with the TPS computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30, range, 87.4% to 100%). For ArcCHECK measurements, the mean passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34, range, 95.8% to 100%). 2D fluence maps with a resolution of 1×1 mm2 showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18, range, 97.0% to100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. Conclusions We have developed a dosimetry program for ViewRay’s patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and

  6. Patient-specific quality assurance for the delivery of (60)Co intensity modulated radiation therapy subject to a 0.35-T lateral magnetic field.

    Science.gov (United States)

    Li, H Harold; Rodriguez, Vivian L; Green, Olga L; Hu, Yanle; Kashani, Rojano; Wooten, H Omar; Yang, Deshan; Mutic, Sasa

    2015-01-01

    This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging-guided RT device. The program consisted of: (1) a 1-dimensional multipoint ionization chamber measurement using a customized 15-cm(3) cube-shaped phantom; (2) 2-dimensional (2D) radiographic film measurement using a 30- × 30- × 20-cm(3) phantom with multiple inserted ionization chambers; (3) quasi-3D diode array (ArcCHECK) measurement with a centrally inserted ionization chamber; (4) 2D fluence verification using machine delivery log files; and (5) 3D Monte Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Ionization chamber measurements agreed well with treatment planning system (TPS)-computed doses in all phantom geometries where the mean ± SD difference was 0.0% ± 1.3% (n=102; range, -3.0%-2.9%). Film measurements also showed excellent agreement with the TPS-computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30; range, 87.4%-100%). For ArcCHECK measurements, the mean ± SD passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34; range, 95.8%-100%). 2D fluence maps with a resolution of 1 × 1 mm(2) showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18; range, 97.0%-100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. We developed a dosimetry program for ViewRay's patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and action limits for ViewRay's IMRT QA. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Patient-Specific Quality Assurance for the Delivery of 60Co Intensity Modulated Radiation Therapy Subject to a 0.35-T Lateral Magnetic Field

    International Nuclear Information System (INIS)

    Li, H. Harold; Rodriguez, Vivian L.; Green, Olga L.; Hu, Yanle; Kashani, Rojano; Wooten, H. Omar; Yang, Deshan; Mutic, Sasa

    2015-01-01

    Purpose: This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging-guided RT device. Methods and Materials: The program consisted of: (1) a 1-dimensional multipoint ionization chamber measurement using a customized 15-cm 3 cube-shaped phantom; (2) 2-dimensional (2D) radiographic film measurement using a 30- × 30- × 20-cm 3 phantom with multiple inserted ionization chambers; (3) quasi-3D diode array (ArcCHECK) measurement with a centrally inserted ionization chamber; (4) 2D fluence verification using machine delivery log files; and (5) 3D Monte Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Results: Ionization chamber measurements agreed well with treatment planning system (TPS)-computed doses in all phantom geometries where the mean ± SD difference was 0.0% ± 1.3% (n=102; range, −3.0%-2.9%). Film measurements also showed excellent agreement with the TPS-computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30; range, 87.4%-100%). For ArcCHECK measurements, the mean ± SD passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34; range, 95.8%-100%). 2D fluence maps with a resolution of 1 × 1 mm 2 showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18; range, 97.0%-100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. Conclusions: We developed a dosimetry program for ViewRay's patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and action limits for ViewRay's IMRT

  8. Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.

    Science.gov (United States)

    Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J

    2010-10-01

    To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.

  9. Substance Abuse in Aging Population

    Directory of Open Access Journals (Sweden)

    Alireza Jazayeri

    2006-10-01

    Full Text Available substance abuse' specially opiates and prescribed drugs are spreading among the older adults. Most of the time it begins as an attempt to medicate chronic pains, medical conditions and loneliness. In other instances, it simply is the continuation of a problem that begun in young adulthood. But scholars and specialists in both fields of Addiction and Gerontology, rather neglected this fast growing problem, to the extent that we almost have no data on the epidemiology, prevention and treatment modalities among the substance abusing old adults in Iran. This paper reflects the necessity of designing age specific programs to identify and treat this group. Besides, some of the most effictive methods of treatment in other countries are reviewed.

  10. Radioiodination of humic substances

    Energy Technology Data Exchange (ETDEWEB)

    Franke, K.; Kupsch, H. [Inst. of Interdisciplinary Isotope Research, Leipzig (Germany)

    2010-07-01

    The known IODO-GEN trademark -method was adapted for radiolabeling of humic and fulvic acids with {sup 131}I. The water insoluble oxidizing agent 1,3,4,6tetrachloro-3{alpha},6{alpha}-diphenylglycoluril (IODO-GEN trademark) forms an iodous ion species (I{sup +}), which undergoes an electrophilic I/H-substitution on aromatic moieties of the humic and fulvic acids. This method offers mild conditions with a lesser extent of oxidative alterations of the target molecule, accompanied by an easy handling due to the virtual water-insolubility of the oxidizing agent. The method was optimized and different techniques were tested for the purification of the radioiodinated humic material. The yield of the labeling procedure varies between 45 and 75% depending on the provenance of the humic material and the applied purification method. A specific activity up to 40 MBq/mg was achieved. Furthermore, the known inherent photo-susceptibility of the iodinated humic substance and the influence of reducing agents were verified. An additional release of {sup 131}I up to 20% and up to 35%, respectively were observed. (orig.)

  11. Pricing hazardous substance emissions

    Energy Technology Data Exchange (ETDEWEB)

    Staring, Knut; Vennemo, Haakon

    1998-12-31

    This report discusses pricing of emissions to air of several harmful substances. It combines ranking indices for environmentally harmful substances with economic valuation data to yield price estimates. The ranking methods are discussed and a relative index established. Given the relative ranking of the substances, they all become valued by assigning a value to one of them, the `anchor` substance, for which lead is selected. Valuations are provided for 19 hazardous substances that are often subject to environmental regulations. They include dioxins, TBT, etc. The study concludes with a discussion of other categories of substances as well as uncertainties and possible refinements. When the valuations are related to CO, NOx, SOx and PM 10, the index system undervalues these pollutants as compared to other studies. The scope is limited to the outdoor environment and does not include global warming and eutrophication. The indices are based on toxicity and so do not apply to CO{sub 2} or other substances that are biologically harmless. The index values are not necessarily valid for all countries and should be considered as preliminary. 18 refs., 6 tabs.

  12. Pricing hazardous substance emissions

    Energy Technology Data Exchange (ETDEWEB)

    Staring, Knut; Vennemo, Haakon

    1997-12-31

    This report discusses pricing of emissions to air of several harmful substances. It combines ranking indices for environmentally harmful substances with economic valuation data to yield price estimates. The ranking methods are discussed and a relative index established. Given the relative ranking of the substances, they all become valued by assigning a value to one of them, the `anchor` substance, for which lead is selected. Valuations are provided for 19 hazardous substances that are often subject to environmental regulations. They include dioxins, TBT, etc. The study concludes with a discussion of other categories of substances as well as uncertainties and possible refinements. When the valuations are related to CO, NOx, SOx and PM 10, the index system undervalues these pollutants as compared to other studies. The scope is limited to the outdoor environment and does not include global warming and eutrophication. The indices are based on toxicity and so do not apply to CO{sub 2} or other substances that are biologically harmless. The index values are not necessarily valid for all countries and should be considered as preliminary. 18 refs., 6 tabs.

  13. Comparison of Gafchromic EBT2 and EBT3 for patient-specific quality assurance: Cranial stereotactic radiosurgery using volumetric modulated arc therapy with multiple noncoplanar arcs

    Energy Technology Data Exchange (ETDEWEB)

    Fiandra, Christian; Fusella, Marco; Filippi, Andrea Riccardo; Ricardi, Umberto; Ragona, Riccardo [Department of Oncology, Radiation Oncology Unit, University of Torino, Turin 10126 (Italy); Giglioli, Francesca Romana [Medical Physics Unit, Azienda Ospedaliera Città della Salute e della Scienza, Turin 10126 (Italy); Mantovani, Cristina [Radiation Oncology Department, Azienda Ospedaliera Città della Salute e della Scienza, Turin 10126 (Italy)

    2013-08-15

    Purpose: Patient-specific quality assurance in volumetric modulated arc therapy (VMAT) brain stereotactic radiosurgery raises specific issues on dosimetric procedures, mainly represented by the small radiation fields associated with the lack of lateral electronic equilibrium, the need of small detectors and the high dose delivered (up to 30 Gy). Gafchromic{sup TM} EBT2 and EBT3 films may be considered the dosimeter of choice, and the authors here provide some additional data about uniformity correction for this new generation of radiochromic films.Methods: A new analysis method using blue channel for marker dye correction was proposed for uniformity correction both for EBT2 and EBT3 films. Symmetry, flatness, and field-width of a reference field were analyzed to provide an evaluation in a high-spatial resolution of the film uniformity for EBT3. Absolute doses were compared with thermoluminescent dosimeters (TLD) as baseline. VMAT plans with multiple noncoplanar arcs were generated with a treatment planning system on a selected pool of eleven patients with cranial lesions and then recalculated on a water-equivalent plastic phantom by Monte Carlo algorithm for patient-specific QA. 2D quantitative dose comparison parameters were calculated, for the computed and measured dose distributions, and tested for statistically significant differences.Results: Sensitometric curves showed a different behavior above dose of 5 Gy for EBT2 and EBT3 films; with the use of inhouse marker-dye correction method, the authors obtained values of 2.5% for flatness, 1.5% of symmetry, and a field width of 4.8 cm for a 5 × 5 cm{sup 2} reference field. Compared with TLD and selecting a 5% dose tolerance, the percentage of points with ICRU index below 1 was 100% for EBT2 and 83% for EBT3. Patients analysis revealed statistically significant differences (p < 0.05) between EBT2 and EBT3 in the percentage of points with gamma values <1 (p= 0.009 and p= 0.016); the percent difference as well as

  14. [Acting out and psychoactive substances: alcohol, drugs, illicit substances].

    Science.gov (United States)

    Gillet, C; Polard, E; Mauduit, N; Allain, H

    2001-01-01

    mental disorders is also very frequent. Multiple substance abuse should be avoided, because potential interactions between two or more drugs are more likely to cause violent behaviour. In the future, a specific treatment of these deleterious phenomena will have to be considered in order to reduce drug-induced iatrogenic behavioural disorders.

  15. EFFECT OF SUBSTANCE (1)

    African Journals Online (AJOL)

    OF HEALTH OFFICER AND MEDICAL STUDENTS OF JIMMA. UNIVERSITY ... cannabis or marihuana and khat (2, 3). Reports showed that these substances ... mainly through cancer especially lung cancer, of which about 90% of cases are ...

  16. Toxic substances handbook

    Science.gov (United States)

    Junod, T. L.

    1979-01-01

    Handbook, published in conjunction with Toxic Substances Alert Program at NASA Lewis Research Center, profiles 187 toxic chemicals in their relatively pure states and include 27 known or suspected carcinogens.

  17. Toxic substances alert program

    Science.gov (United States)

    Junod, T. L.

    1978-01-01

    A toxicity profile is provided, of 187 toxic substances procured by NASA Lewis Research Center during a 3 1/2 year period, including 27 known or suspected carcinogens. The goal of the program is to assure that the center's health and safety personnel are aware of the procurement and use of toxic substances and to alert and inform the users of these materials as to the toxic characteristics and the control measures needed to ensure their safe use. The program also provides a continuing record of the toxic substances procured, who procured them, what other toxic substances the user has obtained in the past, and where similar materials have been used elsewhere at the center.

  18. Epidemiology of Substance Use in Reproductive-Age Women

    Science.gov (United States)

    McHugh, R. Kathryn; Wigderson, Sara; Greenfield, Shelly F.

    2014-01-01

    Synopsis A significant number of women of reproductive age in the U.S. use addictive substances. In 2012 more than 50% reported current use of alcohol, 20% used tobacco products, and approximately 13% used other drugs. Among women, use of these substances is associated with a number of significant medical, psychiatric, and social consequences, and the course of illness may progress more rapidly in women than men. The lifetime prevalence of alcohol and drug use disorders in women is 19.5% and 7.1%, respectively. In addition, as most addictive substances cross the placenta and have deleterious effects on fetal development, substance use has additional potential adverse consequences for women of reproductive age who may become pregnant. Specific barriers to accessing effective substance use treatment exist for women. The prevalence of substance use and evidence of accelerated illness progression in women highlight the importance of universal substance use screening in women in primary care settings. PMID:24845483

  19. A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.

    Directory of Open Access Journals (Sweden)

    Leni Moldovan

    Full Text Available Peripheral blood mononuclear cells (PBMCs, including rare circulating stem and progenitor cells (CSPCs, have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene, defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03 with age (R2 = -0.23, vascular stiffness (R2 = -0.24, and central aortic pressure (R2 = -0.19 and positively correlated with body mass index (R2 = 0.72, in women. The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional

  20. Role of parenting styles in adolescent substance use: results from a Swedish longitudinal cohort study

    OpenAIRE

    Berge, J; Sundell, K; ?jehagen, A; H?kansson, A

    2016-01-01

    Objective Adolescent substance use is an area of concern because early substance use is associated with a higher risk of adverse outcomes. Parenting style, defined as the general style of parenting, as well as substance-specific parenting practices may influence children's substance use behaviour. The present study aims to probe the impact of parenting style on adolescent substance use. Method A cohort of 1268 adolescents (48% girls), aged 12?13?years at baseline, from 21 junior high schools ...

  1. Alcohol and Substance Use Disorders in DSM-5

    Directory of Open Access Journals (Sweden)

    Gulcan Gulec

    2015-12-01

    Full Text Available When we compare the categories about alcohol, and substance-related disorders in DSM-IV and DSM-5, the new category, named addictive disorders is the most striking change. Only gambling disorder have been identified currently in this category. This may be the most remarkable change among the changes in the DSM-5. Because the expansion of the existing diagnostic criteria may cause the assessment of and lsquo;normal behavior' as a disorder. Additionally, withdrawal of caffeine and cannabis are defined in the DSM-5. Disorders collected under the title of substance-related disorders in the DSM-IV were collected under the name of substance-related and addictive disorders in the DSM-5. Specific criterias for substance abuse and substance addiction have been combined into the name of "substance use disorders". In substance abuse, "experienced legal problems" criteria was removed and "a strong desire or urge or craving for substance use" criteria has been introduced. Henceforth, substance abuse is defined as a mild form of substance use disorders in the DSM-5. A change in the prevalence of substance use disorders should be investigated by the new researches.

  2. The influence of resistance exercise with emphasis on specific contractions (concentric vs. eccentric on muscle strength and post-exercise autonomic modulation: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Mariana O. Gois

    2014-01-01

    Full Text Available Background: Compared to eccentric contractions, concentric contractions result in higher cardiovascular stress. However, we do not know how these two types of contractions influence cardiac autonomic modulation during the post-exercise recovery period. Objective: to compare the effect of resistance training that is performed with concentric vs. eccentric emphasis on muscle strength and on post-exercise recovery which was assessed by examining heart rate variability (HRV, for the knee extensor muscle group in young healthy adults. Methods: For this study, 105 men between 18 and 30 years of age were randomized into 4 groups: concentric control (CONCC, eccentric control (ECCC, concentric training (CONCT and eccentric training (ECCT. The CONCC and ECCC groups underwent one session of resistance exercise (RE using the knee extensor muscle group (3 sets of 1 repetition at 100% of the maximal repetition [1MR] and the CONCT and ECCT groups performed 10 training sessions. The HRV was analyzed at baseline and across four recovery periods (T1, T2, T3 and T4. Results: The ECCT group exhibited increased muscle strength at the end of the study. Regarding cardiac autonomic modulation, the CONCC and ECCC groups exhibited increases in overall variability (SDNN and SD2 at T1 compared to baseline, and the ECCT group demonstrated increases in variables reflecting vagal modulation and the recovery process (RMSSD, SD1 and HF [ms2] at T1, T2 and T4 compared to baseline. Conclusions: Resistance training with emphasis on eccentric contractions promoted strength gain and an increase in cardiac vagal modulation during recovery compared to baseline.

  3. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

    OpenAIRE

    Zhang, Yunpeng; Liu, Wei; Xu, Yanjun; Li, Chunquan; Wang, Yingying; Yang, Haixiu; Zhang, Chunlong; Su, Fei; Li, Yixue; Li, Xia

    2015-01-01

    Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it i...

  4. Adolescent Suicidal Behavior and Substance Use: Developmental Mechanisms

    Directory of Open Access Journals (Sweden)

    Donald M. Dougherty

    2008-01-01

    Full Text Available Adolescent suicidal behaviors and substance use are disturbingly common. Research suggests overlap of some of the etiological mechanisms for both adolescent suicidal behavior and substance use, yet clear understanding of the complex relations between these behaviors and their causal underpinnings is lacking. A growing body of evidence and a diathesis model (Mann et al. 1999; Mann, 2003 highlight the importance of impulse control as a proximal risk factor for adolescent suicidal and substance use behaviors. This literature review extends current theory on the relationships between adolescent suicidal behavior and substance use by: (1 examining how, when, and to what extent adolescent development is affected by poor impulse control, stressful life events, substance use behavior, and biological factors; (2 presenting proposed causal mechanisms by which these risk factors interact to increase risk for suicidal behaviors and substance use; and (3 proposing specific new hypotheses to extend the diathesis model to adolescents at risk for suicide and substance use. More specifically, new hypotheses are presented that predict bidirectional relationships between stressful life events and genetic markers of 5-HT dysregulation; substance use behavior and impulsivity; and substance use behavior and suicide attempts. The importance of distinguishing between different developmental trajectories of suicidal and substance use behaviors, and the effects of specific risk and protective mechanisms are discussed. Use of new statistical approaches that provide for the comparison of latent growth curves and latent class models is recommended to identify differences in developmental trajectories of suicidal behavior and substance use. Knowledge gained from these prospective longitudinal methods should lead to greater understanding on the timing, duration, and extent to which specific risk and protective factors influence the outcomes of suicidal behavior and substance

  5. Substance abuse in anaesthetists.

    Science.gov (United States)

    Garcia-Guasch, Roser; Roigé, Jaume; Padrós, Jaume

    2012-04-01

    Anaesthesiologists have a significantly higher frequency of substance abuse by a factor of nearly 3 when compared with other physicians. This is still a current problem that must be reviewed. Many hypotheses have been formulated to explain why anaesthesiologists appear to be more susceptible to substance abuse than other medical professionals (genetic differences in sensitivity to opioids, stress, the association between chemical dependence and other psychopathology or the second-hand exposure hypothesis). Environmental exposure and sensitization may be an important risk factor in physician addiction. There is a long debate about returning to work for an anaesthetist who has been depending on opioid drugs, and recent debates are discussed. Institutional efforts have been made in many countries and physician health programmes have been developed. As drug abuse among anaesthesiologists has continued, new studies have been conducted to know the theories about susceptibility. Written substance abuse policies and controls must be taken in place and in all countries.

  6. Detection of diffusible substances

    Energy Technology Data Exchange (ETDEWEB)

    Warembourg, M [Lille-1 Univ., 59 - Villeneuve-d' Ascq (France)

    1976-12-01

    The different steps of a radioautographic technique for the detection of diffusible substances are described. Using this radioautographic method, the topographic distribution of estradiol-concentrating neurons was studied in the nervous system and pituitary of the ovariectomized mouse and guinea-pig. A relatively good morphological preservation of structures can be ascertained on sections from unfixed, unembedded tissues prepared at low temperatures and kept-under relatively low humidity. The translocation or extraction of diffusible substances is avoided by directly mounting of frozen sections on dried photographic emulsion. Since no solvent is used, this technique excludes the major sources of diffusion artifacts and permits to be in favourable conditions for the localization of diffusible substances.

  7. Gender differences in substance use disorders.

    Science.gov (United States)

    Brady, K T; Randall, C L

    1999-06-01

    Despite the fact that the rate of substance abuse and dependence is higher among men than it is among women, the prevalence rates, especially the more recent ones, indicate that a diagnosis of substance abuse is not gender specific. From the emerging literature on gender differences over the past 25 years, male and female substance abusers are clearly not the same. Women typically begin using substances later than do men, are strongly influenced by spouses or boyfriends to use, report different reasons for maintaining the use of the substances, and enter treatment earlier in the course of their illnesses than do men. Importantly, women also have a significantly higher prevalence of comorbid psychiatric disorders, such as depression and anxiety, than do men, and these disorders typically predate the onset of substance-abuse problems. For women, substances such as alcohol may be used to self-medicate mood disturbances, whereas for men, this may not be true. Although these comorbid disorders might complicate treatment for women, women are, in fact, responsive to treatment and do as well as men in follow-up. Gender differences and similarities have significant treatment implications. This is especially true for the telescoping phenomenon, in which the window for intervention between progressive landmarks is shorter for women than for men. This is also true for the gender differences in physical and sexual abuse, as well as other psychiatric comorbidity that is evident in female substance abusers seeking treatment. The barriers to treatment for women are being addressed in many treatment settings to encourage more women to enter treatment, and family and couples therapy are standard therapeutic interventions. Negative consequences associated with substance abuse are different for men and women, and gender-sensitive rating instruments must be used to measure not only the severity of the problem but also to evaluate treatment efficacy. To determine whether gender

  8. Phase III study of the European Organisation for Research and Treatment of Cancer satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and specific complementary outpatient module (EORTC OUT-PATSAT7).

    Science.gov (United States)

    Brédart, A; Anota, A; Young, T; Tomaszewski, K A; Arraras, J I; Moura De Albuquerque Melo, H; Schmidt, H; Friend, E; Bergenmar, M; Costantini, A; Vassiliou, V; Hureaux, J; Marchal, F; Tomaszewska, I M; Chie, W-C; Ramage, J; Beaudeau, A; Conroy, T; Bleiker, E; Kulis, D; Bonnetain, F; Aaronson, N K

    2018-01-01

    Advances in cancer care delivery require revision and further development of questionnaires assessing patients' perceived quality of care. This study pre-tested the revised EORTC satisfaction with cancer care core questionnaire applicable in both the cancer inpatient and outpatient settings, and its new, outpatient-specific complementary module. The process of revision, development of the extended application, and pre-testing of these questionnaires was based on phases I to III of the "EORTC Quality of Life Group Module Development Guidelines." In phase III, patients in 11 countries in four European regions, South America and Asia completed provisional versions of the questionnaires. Fifty-seven relevant issues selected from literature reviews and input from experts were operationalized into provisional items, and subsequently translated into ten languages. Assessment of understanding, acceptability, redundancy and relevance by patients (n = 151) from oncology inpatient wards, and outpatient chemotherapy, radiotherapy and consultation settings, led to retention of, deletion of and merging of 40, 14 and 6 items respectively. Cronbach's alpha coefficients for hypothesized questionnaire scales were above 0.80. Our results provide preliminary support for the 33-item EORTC Satisfaction with cancer care core questionnaire and the 7-item complementary module specific for the outpatient care setting. A large scale phase IV cross-cultural psychometric study is now underway. © 2017 John Wiley & Sons Ltd.

  9. Patient-Specific Quality Assurance Using Monte Carlo Dose Calculation and Elekta Log Files for Prostate Volumetric-Modulated Arc Therapy.

    Science.gov (United States)

    Katsuta, Yoshiyuki; Kadoya, Noriyuki; Fujita, Yukio; Shimizu, Eiji; Matsunaga, Kenichi; Sawada, Kinya; Matsushita, Haruo; Majima, Kazuhiro; Jingu, Keiichi

    2017-12-01

    Log file-based methods are attracting increasing interest owing to their ability to validate volumetric-modulated arc therapy outputs with high resolution in the leaf and gantry positions and in delivered dose. Cross-validation of these methods for comparison with measurement-based methods using the ionization chamber/ArcCHECK-3DVH software (version 3.2.0) under the same conditions of treatment anatomy and plan enables an efficient evaluation of this method. In this study, with the purpose of cross-validation, we evaluate the accuracy of a log file-based method using Elekta log files and an X-ray voxel Monte Carlo dose calculation technique in the case of leaf misalignment during prostate volumetric-modulated arc therapy. In this study, 10 prostate volumetric-modulated arc therapy plans were used. Systematic multileaf collimator leaf positional errors (±0.4 and ±0.8 mm for each single bank) were deliberately introduced into the optimized plans. Then, the delivered 3-dimensional doses to a phantom with a certain patient anatomy were estimated by our system. These doses were compared with the ionization chamber dose and the ArcCHECK-3DVH dose. For the given phantom and patient anatomy, the estimated dose strongly coincided with the ionization chamber/ArcCHECK-3DVH dose ( P < .01). In addition, good agreement between the estimated dose and the ionization chamber/ArcCHECK-3DVH dose was observed. The dose estimation accuracy of our system, which combines Elekta log files and X-ray voxel Monte Carlo dose calculation, was evaluated.

  10. A Rhodium(III)-Based Inhibitor of Lysine-Specific Histone Demethylase 1 as an Epigenetic Modulator in Prostate Cancer Cells.

    Science.gov (United States)

    Yang, Chao; Wang, Wanhe; Liang, Jia-Xin; Li, Guodong; Vellaisamy, Kasipandi; Wong, Chun-Yuen; Ma, Dik-Lung; Leung, Chung-Hang

    2017-03-23

    We report herein a novel rhodium(III) complex 1 as a new LSD1 targeting agent and epigenetic modulator. Complex 1 disrupted the interaction of LSD1-H3K4me2 in human prostate carcinoma cells and enhanced the amplification of p21, FOXA2, and BMP2 gene promoters. Complex 1 was selective for LSD1 over other histone demethylases, such as KDM2b, KDM7, and MAO activities, and also showed antiproliferative activity toward human cancer cells. To date, complex 1 is the first metal-based inhibitor of LSD1 activity.

  11. Binding of cationic surfactants to humic substances

    NARCIS (Netherlands)

    Ishiguro, M.; Tan, W.; Koopal, L.K.

    2007-01-01

    Commercial surfactants are introduced into the environment either through waste products or site-specific contamination. The amphiphilic nature of both surfactants and humic substances (HS) leads to their mutual attraction especially when surfactant and HS are oppositely charged. Binding of the

  12. Yellow substance (gelbstoff)

    International Nuclear Information System (INIS)

    Medina, A.

    1988-04-01

    The different values of the mean slope (S) of the absorption coefficient a(λ) of gelbstoff (yellow substance) for each region under the same hydrological conditions and the correlation between the quantity of absorption (CA) of gelbstoff and sea water parameter is discussed. 12 refs, 6 figs, 3 tabs

  13. Adolescent Substance Abuse.

    Science.gov (United States)

    Thorne, Craig R.; DeBlassie, Richard R.

    1985-01-01

    Cummings (1979), citing evidence from the National Institute of Drug Abuse, reports that one of every eleven adult Americans suffers from a severe addictive problem. Drug addiction is epidemic among teenagers; one of every six teenagers suffers from a severe addictive problem. This paper focuses on adolescent drug/substance abuse. (Author)

  14. Method for determining immunochemical substances

    International Nuclear Information System (INIS)

    O'connor, J.

    1980-01-01

    Drawing a method for detecting and measuring a predetermined specifically-bindable immunochemical substance in a liquid sample in a cuvette, comprising the steps of: (A) providing, in an immunoassay technique for the liquid sample in said cuvette, a component comprising a suspension of particles which may be agglutinated or insolubilized in relationship to the presence and concentration of the immunochemical substance in the sample; and (B) determining the presence and concentration of the immunochemical substance by measuring the electromagnetic radiation transmission properties of the sample using a calibrated radiation-measuring apparatus, said apparatus comprising: (1) a suitable electromagnetic radiation source capable of providing radiation at wavelengths equal to or less than the mean diameter of said particles; (2) means for concentrating and collimating radiation from the electromagnetic radiation source to form a beam; (3) means for filtering the beam to (I) eliminate radiation having wavelengths greater than the means diameter of the particles and (II) transmit radiation, which radiation has a range, whereby the upper wavelength is equal to or below the mean diameter of the particles, and the range is of at least about 100nm; (4) means for (I) positioning a sample-containing cuvette and for (II) allowing the filtered beam incident on the cuvette to be transmitted through the cuvette and sample, and for (III) receiving a portion of the filtered beam transmitted through the sample at two or more predetermined angles with respect to the beam; and (5) means for detecting and measuring the portion of the beam transmitted at a predetermined angle

  15. Global issues in volatile substance misuse.

    Science.gov (United States)

    Dell, Colleen Anne; Gust, Steven W; MacLean, Sarah

    2011-01-01

    This special issue of Substance Use & Misuse addresses the public health issue of volatile substance misuse (VSM), the inhalation of gases or vapors for psychoactive effects, assessing the similarities and differences in the products misused, patterns, prevalence, etiologies, and impacts of VSM by examining it through sociocultural epidemiology, neuroscience, and interventions research. The Canadian, US, and Australian guest editors contend that, when compared with other drugs used at a similar prevalence, VSM has attracted relatively little research effort. The authors and editors call for further research to develop evidence-based policies and comprehensive interventions that respect culture and context-specific knowledge.

  16. FASTBUS Snoop Diagnostic Module

    International Nuclear Information System (INIS)

    Walz, H.V.; Downing, R.

    1980-11-01

    Development of the FASTBUS Snoop Module, undertaken as part of the prototype program for the new interlaboratory data bus standard, is described. The Snoop Module resides on a FASTBUS crate segment and provides diagnostic monitoring and testing capability. Communication with a remote host computer is handled independent of FASTBUS through a serial link. The module consists of a high-speed ECL front-end to monitor and single-step FASTBUS cycles, a master-slave interface, and a control microprocessor with serial communication ports. Design details and performance specifications of the prototype module are reported. 9 figures, 1 table

  17. Women and substance abuse: gender, age, and cultural considerations.

    Science.gov (United States)

    Stevens, Sally J; Andrade, Rosi A C; Ruiz, Bridget S

    2009-01-01

    Historically, data has shown that a smaller percentage of women use alcohol and illicit substances compared to men, and that frequency of use has been lower among women compared to use among men. Although this data on usage may be true, researchers also acknowledge that substance use among women has been a hidden issue, one not realistically acknowledged by society, especially prior to the mid-1960s. Along with this, more recent data indicates that rates of substance use among women are increasing. Factors contributing to this increase in substance abuse have begun to receive considerable attention, and recent research suggests that many issues exist that are unique to substance use among women. The purpose of this article is to discuss gender specific considerations in women's substance abuse by examining the history of substance use among women; analyzing gender-specific factors, including physiological factors, trauma-related factors, mental health issues, and cultural considerations that impact on women's substance use; articulating treatment approaches for working with substance abusing women and girls; and providing recommendations for further research in this area.

  18. Aversion substance(s) of the rat coagulating glands

    Science.gov (United States)

    Gawienowski, Anthony M.; Berry, Iver J.; Kennelly, James J.

    1982-01-01

    The aversive substance(s) present in adult male urine were not found in castrate rat urine. Removal of the coagulating glands also resulted in a loss of the aversion compounds. The aversion substances were restored to the urine after androgen treatment of the castrate rats.

  19. Psychiatric Consultation and Substance Use Disorders

    Directory of Open Access Journals (Sweden)

    Sheila Specker

    2009-01-01

    Full Text Available Background A substantial number of patients in general hospitals will evince substance abuse problems but a majority is unlikely to be adequately identified in the referral-consultation process. This failure may preclude patients from receiving effective interventions for substance use disorders. Objectives 1. To evaluate all referred patients for possible substance use disorders. 2. To ascertain the degree of convergence between patients referred for chemical problems and the corresponding DSM diagnosis. 3. To compare demographic data for substance abusing patients and referrals not so classified. 4. To evaluate conditions concomitant with substance use disorders. Method Consecutive one-year referrals (524 to consultation-liaison psychiatric services were scrutinized for chemically-related problems by psychiatric consultants. Results Of the referrals, 176 met criteria for substance use disorders (SUD (57% alcohol; 25% other drugs; 18% both alcohol and other drugs. Persons diagnosed with SUD tended to be younger, male, non-Caucasian, unmarried, and unemployed. They were more likely to be depressed, have liver and other gastrointestinal problems, and to have experienced traumatic events; they also tended to have current financial difficulties. Most were referred for SUD evaluation by personnel in general medicine and family practice. Following psychiatric consultation, SUD designated patients were referred mainly to substance abuse treatment programs. The only variable related to recommended inpatient versus outpatient services for individuals with SUD was the Global Assessment of Functioning Axis (GAF with persons having lower estimated functioning more likely to be referred for inpatient interventions. Conclusions These data are similar to the results of past studies in this area. Unlike previous investigations in the domain of consultative-liaison psychiatry, financial stressors and specific consultant recommendations were included in data

  20. Psychiatric Consultation and Substance Use Disorders

    Directory of Open Access Journals (Sweden)

    Sheila Specker

    2009-11-01

    Full Text Available Background: A substantial number of patients in general hospitals will evince substance abuse problems but a majority is unlikely to be adequately identified in the referral-consultation process. This failure may preclude patients from receiving effective interventions for substance use disorders. Objectives: 1. To evaluate all referred patients for possible substance use disorders. 2. To ascertain the degree of convergence between patients referred for chemical problems and the corresponding DSM diagnosis. 3. To compare demographic data for substance abusing patients and referrals not so classified. 4. To evaluate conditions concomitant with substance use disorders. Method: Consecutive one-year referrals (524 to consultation-liaison psychiatric services were scrutinized for chemically-related problems by psychiatric consultants. Results: Of the referrals, 176 met criteria for substance use disorders (SUD (57% alcohol; 25% other drugs; 18% both alcohol and other drugs. Persons diagnosed with SUD tended to be younger, male, non-Caucasian, unmarried, and unemployed. They were more likely to be depressed, have liver and other gastrointestinal problems, and to have experienced traumatic events; they also tended to have current financial difficulties. Most were referred for SUD evaluation by personnel in general medicine and family practice. Following psychiatric consultation, SUD designated patients were referred mainly to substance abuse treatment programs. The only variable related to recommended inpatient versus outpatient services for individuals with SUD was the Global Assessment of Functioning Axis (GAF with persons having lower estimated functioning more likely to be referred for inpatient interventions. Conclusions: These data are similar to the results of past studies in this area. Unlike previous investigations in the domain of consultative-liaison psychiatry, financial stressors and specific consultant recommendations were included in

  1. Bacterial inclusion bodies as potential synthetic devices for pathogen recognition and a therapeutic substance release.

    Science.gov (United States)

    Talafová, Klaudia; Hrabárová, Eva; Chorvát, Dušan; Nahálka, Jozef

    2013-02-07

    Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances. In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks. The tailored inclusion bodies are promising "nanopills" for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release.

  2. Catechol-O-methyltransferase gene methylation and substance use in adolescents : the TRAILS study

    NARCIS (Netherlands)

    van der Knaap, L. J.; Schaefer, J. M.; Franken, I. H. A.; Verhulst, F. C.; van Oort, F. V. A.; Riese, H.

    Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol-O-methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val(108/158)Met polymorphism modulates COMT activity

  3. Stroke And Substance Abuse

    OpenAIRE

    A Chitsaz

    2017-01-01

    Introduction: stroke in recreational substance users can be an indirect complication, like endocarditis and cardio embolism in parenteral drug users. With some drug like cocaine, stroke appear to be the result of a direct effect. In young subjects without other risk factors provide persuasive evidence for causality . OPIATES: Heroine is the most abused opiate drug, which is administered by injection, by snorting or by smoking. Stroke affects heroin users by diverse mechanisms,. Injec...

  4. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  5. Peripheral Mechanisms of Dental Pain: The Role of Substance P

    Directory of Open Access Journals (Sweden)

    Paola Sacerdote

    2012-01-01

    Full Text Available Current evidence supports the central role of neuropeptides in the molecular mechanisms underlying dental pain. In particular, substance P, a neuropeptide produced in neuron cell bodies localised in dorsal root and trigeminal ganglia, contributes to the transmission and maintenance of noxious stimuli and inflammatory processes. The major role of substance P in the onset of dental pain and inflammation is increasingly being recognised. Well-grounded experimental and clinical observations have documented an increase in substance P concentration in patients affected by caries, pulpitis, or granulomas and in those undergoing standard orthodontic or orthodontic/dental care procedures. This paper focuses on the role of substance P in the induction and maintenance of inflammation and dental pain, in order to define future lines of research for the evaluation of therapeutic strategies aimed at modulating the complex effects of this mediator in oral tissues.

  6. Passing the Baton: A Collaborative Approach to Development and Implementation of Context-Specific Modules for Graduate Teaching Assistants in Cognate Disciplines

    Science.gov (United States)

    O'Neill, Geraldine; McNamara, Martin

    2016-01-01

    A systematic approach to the training of graduate teaching assistants (GTAs) is required to meet the challenges posed by growing numbers of undergraduate and graduate students. At University College Dublin, educational developers and academic staff across six schools collaborated on the design and phased implementation of context-specific GTA…

  7. Tissue- and stage-specific Wnt target gene expression is controlled subsequent to beta-catenin recruitment to cis-regulatory modules

    NARCIS (Netherlands)

    Nakamura, Y.; de Paiva Alves, E.; Veenstra, G.J.C.; Hoppler, S.

    2016-01-01

    Key signalling pathways, such as canonical Wnt/beta-catenin signalling, operate repeatedly to regulate tissue- and stage-specific transcriptional responses during development. Although recruitment of nuclear beta-catenin to target genomic loci serves as the hallmark of canonical Wnt signalling,

  8. Is Poor Frequency Modulation Detection Linked to Literacy Problems? A Comparison of Specific Reading Disability and Mild to Moderate Sensorineural Hearing Loss

    Science.gov (United States)

    Halliday, L. F.; Bishop, D. V. M.

    2006-01-01

    Specific reading disability (SRD) is now widely recognised as often being caused by phonological processing problems, affecting analysis of spoken as well as written language. According to one theoretical account, these phonological problems are due to low-level problems in auditory perception of dynamic acoustic cues. Evidence for this has come…

  9. Neonatal modulation of serum cytokine profiles by a specific mixture of anti-inflammatory neutral and acidic oligosaccharides in preterm infants

    NARCIS (Netherlands)

    van den Berg, Jolice P.; van Zwieteren, Ninke; Westerbeek, Elisabeth A. M.; Garssen, Johan; van Elburg, Ruurd M.

    2013-01-01

    Infections are common in preterm infants and cause differences in cytokine levels. Aim of this study was to measure cytokine levels in preterm infants during the first year of life and to determine the effect of feeding a specific non-digestible carbohydrate mixture (scGOS/lcFOS/pAOS). Furthermore,

  10. Substance use in pregnancy.

    Science.gov (United States)

    Wong, Suzanne; Ordean, Alice; Kahan, Meldon

    2011-04-01

    To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy. Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to

  11. Public perceptions of behavioral and substance addictions.

    Science.gov (United States)

    Lang, Brent; Rosenberg, Harold

    2017-02-01

    Most of the research on public perceptions of people with addictive disorders has focused on alcohol and illicit drugs, rather than addiction to behavioral activities. To expand the range of addictive behaviors and types of perceptions studied, we designed the present study to assess the lay public's definitions of and willingness to affiliate with people described as addicted to 1 of 2 specific behaviors (i.e., pornography or gambling) or 1 of 3 specific substances (i.e., alcohol, marijuana, or heroin). A nationwide convenience sample (N = 612) of American adults completed online questionnaires during the summer of 2015. Participants rated heroin as more addictive than the other drugs and behaviors and, despite differences among the conditions, were generally unwilling to affiliate with an individual addicted to any of the 2 behaviors or 3 substances. When asked to rate different potential indications of addiction, participants endorsed behavioral signs of impaired control and physiological and psychological dependence as more indicative of all 5 types of addiction than desire to use the substance or engage in the addictive behavior. Despite recent efforts to increase public knowledge about addictive disorders, members of the public continue to endorse some attitudes indicative of stigmatization toward people with selected substance and behavioral addictions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. DSM-5 Criteria for Substance Use Disorders: Recommendations and Rationale

    Science.gov (United States)

    Hasin, Deborah S.; O’Brien, Charles P.; Auriacombe, Marc; Borges, Guilherme; Bucholz, Kathleen; Budney, Alan; Compton, Wilson M.; Crowley, Thomas; Ling, Walter; Petry, Nancy M.; Schuckit, Marc; Grant, Bridget F.

    2013-01-01

    Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndromes for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions. This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available. PMID:23903334

  13. DSM-5 criteria for substance use disorders: recommendations and rationale.

    Science.gov (United States)

    Hasin, Deborah S; O'Brien, Charles P; Auriacombe, Marc; Borges, Guilherme; Bucholz, Kathleen; Budney, Alan; Compton, Wilson M; Crowley, Thomas; Ling, Walter; Petry, Nancy M; Schuckit, Marc; Grant, Bridget F

    2013-08-01

    Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndromes for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions.This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available.

  14. Treating patients with bipolar disorder and substance dependence: lessons learned.

    Science.gov (United States)

    Weiss, Roger D

    2004-12-01

    Although bipolar disorder is the Axis I psychiatric disorder associated with the highest rate of co-occurring substance use disorders, little research has focused on treatments specifically designed for these patients. The author and his colleagues have developed and studied Integrated Group Therapy (IGT) for this population. This paper describes common themes that have emerged in carrying out IGT for patients with bipolar disorder and substance dependence. These include the strong emphasis on depression, as opposed to mania; the predominance of hopelessness; specific patterns of medication noncompliance; and the implications of patients' labeling their substance use as self-medication. Therapeutic aspects involved in addressing these themes are discussed.

  15. Is There an Advantage in Designing Adapted, Patient-Specific PTV Margins in Intensity Modulated Proton Beam Therapy for Prostate Cancer?

    International Nuclear Information System (INIS)

    Góra, Joanna; Stock, Markus; Lütgendorf-Caucig, Carola; Georg, Dietmar

    2013-01-01

    Purpose: To investigate robust margin strategies in intensity modulated proton therapy to account for interfractional organ motion in prostate cancer. Methods and Materials: For 9 patients, one planning computed tomography (CT) scan and daily and weekly cone beam CTs (CBCTs) were acquired and coregistered. The following planning target volume (PTV) approaches were investigated: a clinical target volume (CTV) delineated on the planning CT (CTV ct ) plus 10-mm margin (PTV 10mm ); a reduced PTV (PTV Red ): CTV ct plus 5 mm in the left-right (LR) and anterior-posterior (AP) directions and 8 mm in the inferior-superior (IS) directions; and a PTV Hull method: the sum of CTV ct and CTVs from 5 CBCTs from the first week plus 3 mm in the LR and IS directions and 5 mm in the AP direction. For each approach, separate plans were calculated using a spot-scanning technique with 2 lateral fields. Results: Each approach achieved excellent target coverage. Differences were observed in volume receiving 98% of the prescribed dose (V 98% ) where PTV Hull and PTV Red results were superior to the PTV 10mm concept. The PTV Hull approach was more robust to organ motion. The V 98% for CTVs was 99.7%, whereas for PTV Red and PTV 10mm plans, V 98% was 98% and 96.1%, respectively. Doses to organs at risk were higher for PTV Hull and PTV 10mm plans than for PTV Red , but only differences between PTV 10mm and PTV Red were significant. Conclusions: In terms of organ sparing, the PTV 10mm method was inferior but not significantly different from the PTV Red and PTV Hull approaches. PTV Hull was most insensitive to target motion

  16. Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy.

    Science.gov (United States)

    Pieragostino, Damiana; Agnifili, Luca; Fasanella, Vincenzo; D'Aguanno, Simona; Mastropasqua, Rodolfo; Di Ilio, Carmine; Sacchetta, Paolo; Urbani, Andrea; Del Boccio, Piero

    2013-06-01

    Primary open angle glaucoma (POAG) is one of the main causes of irreversible blindness worldwide. The pathogenesis of POAG is still unclear. Alteration and sclerosis of trabecular meshwork with changes in aqueous humor molecular composition seem to play the key role. Increased intraocular pressure is widely known to be the main risk factor for the onset and progression of the disease. Unfortunately, the early diagnosis of POAG still remains the main challenge. In order to provide insight into the patho-physiology of glaucoma, here we report a shotgun proteomics approach to tears of patients with POAG naïve to therapy. Our proteomics results showed 27 differential tear proteins in POAG vs. CTRL comparison (25 up regulated proteins in the POAG group and two unique proteins in the CTRL group), 16 of which were associated with inflammatory response, free radical scavenging, cell-to-cell signaling and interaction. Overall the protein modulation shown in POAG tears proves the involvement of biochemical networks linked to inflammation. Among all regulated proteins, a sub-group of 12 up-regulated proteins in naïve POAG patients were found to be down-regulated in medically controlled POAG patients treated with prostanoid analogues (PGA), as reported in our previous work (i.e., lipocalin-1, lysozyme C, lactotransferrin, proline-rich-protein 4, prolactin-inducible protein, zinc-alpha-2-glycoprotein, polymeric immunoglobulin receptor, cystatin S, Ig kappa chain C region, Ig alpha-2 chain C region, immunoglobulin J chain, Ig alpha-1 chain C region). In summary, our findings indicate that the POAG tears protein expression is a mixture of increased inflammatory proteins that could be potential biomarkers of the disease, and their regulation may be involved in the mechanism by which PGA are able to decrease the intraocular pressure in glaucoma patients.

  17. Specific binding of prostaglandin E2 to membrane preparations from human skin: receptor modulation by UVB-irradiation and chemical agents

    International Nuclear Information System (INIS)

    Lord, J.T.; Ziboh, V.A.

    1979-01-01

    Human skin membranes bind prostaglandin E2 (PGE2) with high affinity and specificity. This binding is inhibited by trypsin or heat treatment suggesting that PGE2 receptors have protein components. Exposure of the membranes to ultraviolet irradiation (UVB) resulted in the loss of the membrane binding capacity for PGE2. This UVB-inhibitory effect could be prevented by a known protein sulfhydryl-oxidizing agent and a known lipid anti-oxidant

  18. Amphioxus Sp5 is a member of a conserved Specificity Protein complement and is modulated by Wnt/beta-catenin signalling

    Czech Academy of Sciences Publication Activity Database

    Dailey, S.C.; Kozmiková, Iryna; Somorjai, I.M.L.

    2017-01-01

    Roč. 61, č. 10-12 (2017), s. 723-732 ISSN 0214-6282 R&D Projects: GA ČR GC15-21285J Institutional support: RVO:68378050 Keywords : Specificity protein * Brachyury * Branchiostoma * Wnt * Sp5 Subject RIV: EB - Gene tics ; Molecular Biology OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 1.981, year: 2016

  19. Changes in the Excitability of Neocortical Neurons in a Mouse Model of Amyotrophic Lateral Sclerosis Are Not Specific to Corticospinal Neurons and Are Modulated by Advancing Disease.

    Science.gov (United States)

    Kim, Juhyun; Hughes, Ethan G; Shetty, Ashwin S; Arlotta, Paola; Goff, Loyal A; Bergles, Dwight E; Brown, Solange P

    2017-09-13

    Cell type-specific changes in neuronal excitability have been proposed to contribute to the selective degeneration of corticospinal neurons in amyotrophic lateral sclerosis (ALS) and to neocortical hyperexcitability, a prominent feature of both inherited and sporadic variants of the disease, but the mechanisms underlying selective loss of specific cell types in ALS are not known. We analyzed the physiological properties of distinct classes of cortical neurons in the motor cortex of hSOD1 G93A mice of both sexes and found that they all exhibit increases in intrinsic excitability that depend on disease stage. Targeted recordings and in vivo calcium imaging further revealed that neurons adapt their functional properties to normalize cortical excitability as the disease progresses. Although different neuron classes all exhibited increases in intrinsic excitability, transcriptional profiling indicated that the molecular mechanisms underlying these changes are cell type specific. The increases in excitability in both excitatory and inhibitory cortical neurons show that selective dysfunction of neuronal cell types cannot account for the specific vulnerability of corticospinal motor neurons in ALS. Furthermore, the stage-dependent alterations in neuronal function highlight the ability of cortical circuits to adapt as disease progresses. These findings show that both disease stage and cell type must be considered when developing therapeutic strategies for treating ALS. SIGNIFICANCE STATEMENT It is not known why certain classes of neurons preferentially die in different neurodegenerative diseases. It has been proposed that the enhanced excitability of affected neurons is a major contributor to their selective loss. We show using a mouse model of amyotrophic lateral sclerosis (ALS), a disease in which corticospinal neurons exhibit selective vulnerability, that changes in excitability are not restricted to this neuronal class and that excitability does not increase

  20. Dimensions of Assertiveness: Differential Relationships to Substance Use in Early Adolescence.

    Science.gov (United States)

    Wills, Thomas Ashby; And Others

    1989-01-01

    Tested multidimensional formulation of assertiveness and substance use in 3 metropolitan-area school samples (N=675, N=1,430, and N=5,545) of adolescents including White, Black, and Hispanic students aged 12-14 years. Found Substance-specific Assertiveness inversly associated with substance use and Social Dating Assertiveness positively associated…

  1. Toxic substances: Federal-provincial control. Revised edition. Current issue review No. 88-11E

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, K; Johansen, D

    1993-01-01

    There is widespread public concern about the effect of toxic substances on human health and the environment. This document looks at the federal-provincial control on toxic substances. It specifically examines the control of toxic substances under the Canadian constitution; the political arena; the federal- provincial co-operation; the Green Plan; and the 1991 Auditor General's Report.

  2. The role of substance use motives in the associations between minority stressors and substance use problems among young men who have sex with men.

    Science.gov (United States)

    Feinstein, Brian A; Newcomb, Michael E

    2016-09-01

    Young men who have sex with men (YMSM) report higher rates of substance use than their heterosexual peers and minority stress has been posited as a risk factor for substance use. The associations between specific types of minority stress and substance use have been inconsistent throughout the literature and few studies have examined mechanisms underlying these associations. Drawing on minority stress theory and the motivational model of alcohol use, we propose that one mechanism underlying these associations may be people's motivations for using substances, including using substances to cope with negative emotions and to enhance pleasure. The goals of the current study were: (1) to examine the associations among minority stressors, substance use motives, and substance use problems; and (2) to examine substance use motives as mediators of the associations between minority stressors and substance use problems. Baseline self-report data were used from a cohort of 370 YMSM enrolled in a larger study of substance use and sexual behavior. Results indicated that using marijuana to cope mediated the association between victimization and marijuana use problems. Using other drugs to cope mediated the associations between victimization and drug use problems and between internalized stigma and drug use problems. Drinking to cope and to enhance pleasure mediated the association between internalized stigma and alcohol use problems. In sum, substance use motives, especially using substances to cope, act as mechanisms through which certain types of minority stress influence substance use problems among YMSM.

  3. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial.

    Directory of Open Access Journals (Sweden)

    Christian Prebensen

    Full Text Available Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL. Patients in each of the two study groups were randomized to receive 90 mg qd of the cyclooxygenase-2 inhibitor etoricoxib for six months, two weeks or to a control arm, respectively. T cell activation status, HIV Gag-specific T cell responses and plasma inflammatory markers, tryptophan metabolism and thrombin generation were analyzed at baseline and after four months. In addition, patients received tetanus toxoid, conjugated pneumococcal and seasonal influenza vaccines, to which IgG responses were determined after four weeks. In ART-naïve patients, etoricoxib reduced the density of the activation marker CD38 in multiple CD8+ T cell subsets, improved Gag-specific T cell responses, and reduced in vitro plasma thrombin generation, while no effects were seen on plasma markers of inflammation or tryptophan metabolism. No significant immunological effects of etoricoxib were observed in ART-treated patients. Patients receiving long-term etoricoxib treatment had poorer tetanus toxoid and conjugated pneumococcal vaccine responses than those receiving short-course etoricoxib. Cyclooxygenase-2 inhibitors may attenuate harmful immune activation in HIV-infected patients without access to ART.

  4. Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections.

    Directory of Open Access Journals (Sweden)

    Jessica F Toro

    Full Text Available The response of antibody-secreting cells (ASC induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6-12 months old and children (1-14 years old infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI, the total and envelope (E protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = -0.59, P = 0.03. However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI. IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue.

  5. Rexinoid Bexarotene Modulates Triglyceride but not Cholesterol Metabolism via Gene-Specific Permissivity of the RXR/LXR Heterodimer in the Liver

    DEFF Research Database (Denmark)

    Lalloyer, Fanny; Pedersen, Thomas Åskov; Gross, Barbara

    2009-01-01

    OBJECTIVE: Bexarotene (Targretin) is a clinically used antitumoral agent which exerts its action through binding to and activation of the retinoid-X-receptor (RXR). The most frequent side-effect of bexarotene administration is an increase in plasma triglycerides, an independent risk factor...... controlling cholesterol homeostasis. CONCLUSIONS: These findings demonstrate that the hypertriglyceridemic action of bexarotene occurs via the RXR/LXR heterodimer and show that RXR heterodimers can act with a selective permissivity on target genes of specific metabolic pathways in the liver....

  6. Impact of Contextual Factors and Substance Characteristics on Perspectives toward Cognitive Enhancement

    OpenAIRE

    Sattler, Sebastian; Forlini, Cynthia; Racine, ?ric; Sauer, Carsten

    2013-01-01

    Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimental...

  7. The specificity of Av3 sea anemone toxin for arthropods is determined at linker DI/SS2-S6 in the pore module of target sodium channels.

    Science.gov (United States)

    Gur Barzilai, Maya; Kahn, Roy; Regev, Noa; Gordon, Dalia; Moran, Yehu; Gurevitz, Michael

    2014-10-15

    Av3 is a peptide neurotoxin from the sea anemone Anemonia viridis that shows specificity for arthropod voltage-gated sodium channels (Navs). Interestingly, Av3 competes with a scorpion α-toxin on binding to insect Navs and similarly inhibits the inactivation process, and thus has been classified as 'receptor site-3 toxin', although the two peptides are structurally unrelated. This raises questions as to commonalities and differences in the way both toxins interact with Navs. Recently, site-3 was partly resolved for scorpion α-toxins highlighting S1-S2 and S3-S4 external linkers at the DIV voltage-sensor module and the juxtaposed external linkers at the DI pore module. To uncover channel determinants involved in Av3 specificity for arthropods, the toxin was examined on channel chimaeras constructed with the external linkers of the mammalian brain Nav1.2a, which is insensitive to Av3, in the background of the Drosophila DmNav1. This approach highlighted the role of linker DI/SS2-S6, adjacent to the channel pore, in determining Av3 specificity. Point mutagenesis at DI/SS2-S6 accompanied by functional assays highlighted Trp404 and His405 as a putative point of Av3 interaction with DmNav1. His405 conservation in arthropod Navs compared with tyrosine in vertebrate Navs may represent an ancient substitution that explains the contemporary selectivity of Av3. Trp404 and His405 localization near the membrane surface and the hydrophobic bioactive surface of Av3 suggest that the toxin possibly binds at a cleft by DI/S6. A partial overlap in receptor site-3 of both toxins nearby DI/S6 may explain their binding competition capabilities.

  8. Attachment of Salmonella strains to a plant cell wall model is modulated by surface characteristics and not by specific carbohydrate interactions.

    Science.gov (United States)

    Tan, Michelle Sze-Fan; Moore, Sean C; Tabor, Rico F; Fegan, Narelle; Rahman, Sadequr; Dykes, Gary A

    2016-09-15

    Processing of fresh produce exposes cut surfaces of plant cell walls that then become vulnerable to human foodborne pathogen attachment and contamination, particularly by Salmonella enterica. Plant cell walls are mainly composed of the polysaccharides cellulose, pectin and hemicelluloses (predominantly xyloglucan). Our previous work used bacterial cellulose-based plant cell wall models to study the interaction between Salmonella and the various plant cell wall components. We demonstrated that Salmonella attachment was favoured in the presence of pectin while xyloglucan had no effect on its attachment. Xyloglucan significantly increased the attachment of Salmonella cells to the plant cell wall model only when it was in association with pectin. In this study, we investigate whether the plant cell wall polysaccharides mediate Salmonella attachment to the bacterial cellulose-based plant cell wall models through specific carbohydrate interactions or through the effects of carbohydrates on the physical characteristics of the attachment surface. We found that none of the monosaccharides that make up the plant cell wall polysaccharides specifically inhibit Salmonella attachment to the bacterial cellulose-based plant cell wall models. Confocal laser scanning microscopy showed that Salmonella cells can penetrate and attach within the tightly arranged bacterial cellulose network. Analysis of images obtained from atomic force microscopy revealed that the bacterial cellulose-pectin-xyloglucan composite with 0.3 % (w/v) xyloglucan, previously shown to have the highest number of Salmonella cells attached to it, had significantly thicker cellulose fibrils compared to other composites. Scanning electron microscopy images also showed that the bacterial cellulose and bacterial cellulose-xyloglucan composites were more porous when compared to the other composites containing pectin. Our study found that the attachment of Salmonella cells to cut plant cell walls was not mediated by

  9. The ISS dangerous substances classification and labelling database

    International Nuclear Information System (INIS)

    Di Prospero Fanghella, P.; Izzo, P.; Morassi, E.

    2008-01-01

    The database contains information about the substances marketed in the European Union at present. About 8000 out of 100000 substances on the market are listed in Annex I (Directive 67/548/EC), the published list of substances with a harmonised classification and labelling. For each entry the database gives the following details: name, CAS number, EC number, classification, labelling, specific concentration limits, reference to the last amended EU and national law. There is also a section where the legislative frame is reported together with the EU Directives and the corresponding national implementation decrees. In addition to searching a substance by name/part of the name or identifying numbers the query can be done by symbols, R and S phrases, substance categories [it

  10. Social dimensions of adolescent substance use.

    Science.gov (United States)

    Sutherland, I; Shepherd, J P

    2001-03-01

    The aim of this study was to explore in detail the relationship between various social aspects of young people's lives and substance use and differences in the degree of influence exerted by the different social factors as a function of age. Design, setting, participants. The study was a survey of pupils aged 11-16 in a stratified sample of five English schools. Data from 4516 participants were obtained in relation to their cigarette, alcohol and illicit drug use and their contact with the police, perceived academic achievements and future expectations, religious beliefs, family structure, the importance of family versus peer opinions and suspension from school. Cumulative, age-specific preferences of substance misuse were compared. Logistic regression was used to rank the various risk factors. Substantial differences were found between substance users and non-users and the various risk factors being examined. For example, of those who had only been in trouble with the police, 18.8% used illegal drugs compared with 1.6% of those who had not had a police contact and who had no other risk factors. Many of these relationships were age-sensitive. For instance, the negative relationship between belief in God and illicit drug use became stronger as age increased (non-believers: y = 8.1886x - 9.16 R(2) = 0.9484; believers: y = 5.1514x - 8.08 R(2) = 0.9247). These results suggest that, within this sample of English adolescents, there was a strong relationship between substance use and the social factors examined. Although there were differences depending upon whether cigarette, alcohol or illicit drug use was being modelled, logistic regression indicated that the social factors could be ranked in the following order of importance: concurrent use of the second and third substances, having been in trouble with the police, perceived poor academic performance and low future academic expectations, a lack of religious belief, coming from a non-intact family, favouring peer over

  11. Substance abuse and child maltreatment.

    Science.gov (United States)

    Wells, Kathryn

    2009-04-01

    Pediatricians and other medical providers caring for children need to be aware of the dynamics in the significant relationship between substance abuse and child maltreatment. A caregiver's use and abuse of alcohol, marijuana, heroin, cocaine, methamphetamine, and other drugs place the child at risk in multiple ways. Members of the medical community need to understand these risks because the medical community plays a unique and important role in identifying and caring for these children. Substance abuse includes the abuse of legal drugs as well as the use of illegal drugs. The abuse of legal substances may be just as detrimental to parental functioning as abuse of illicit substances. Many substance abusers are also polysubstance users and the compounded effect of the abuse of multiple substances may be difficult to measure. Often other interrelated social features, such as untreated mental illness, trauma history, and domestic violence, affect these families.

  12. Gang youth, substance use, and drug normalization

    OpenAIRE

    Sanders, Bill

    2012-01-01

    Gang membership is an indicator of chronic substance use.1 Evidence from North America and Europe indicates that gang youth, in comparison to their non-gang peers, are more likely to report alcohol and illicit drug use (Bendixen, Endresen, & Olweus, 2006; Gatti, Tremblay, Vitaro, & McDuff, 2005; Gordon, et al., 2004; Hall, Thornberry, & Lizotte, 2006; Sharp, Aldridge, & Medina, 2006). Qualitative studies focusing specifically on gang members have also noted high frequencies of lifetime rates ...

  13. Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli.

    Science.gov (United States)

    Bartelt, Luther A; Bolick, David T; Mayneris-Perxachs, Jordi; Kolling, Glynis L; Medlock, Gregory L; Zaenker, Edna I; Donowitz, Jeffery; Thomas-Beckett, Rose Viguna; Rogala, Allison; Carroll, Ian M; Singer, Steven M; Papin, Jason; Swann, Jonathan R; Guerrant, Richard L

    2017-07-01

    Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens in malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), we provide new insights into intersecting pathogen-specific mechanisms that enhance malnutrition. We show for the first time that during protein malnutrition, the intestinal microbiota permits persistent Giardia colonization and simultaneously contributes to growth impairment. Despite signals of intestinal injury, such as IL1α, Giardia-infected mice lack pro-inflammatory intestinal responses, similar to endemic pediatric Giardia infections. Rather, Giardia perturbs microbial host co-metabolites of proteolysis during growth impairment, whereas host nicotinamide utilization adaptations that correspond with growth recovery increase. EAEC promotes intestinal inflammation and markers of myeloid cell activation. During co-infection, intestinal inflammatory signaling and cellular recruitment responses to EAEC are preserved together with a Giardia-mediated diminishment in myeloid cell activation. Conversely, EAEC extinguishes markers of host energy expenditure regulatory responses to Giardia, as host metabolic adaptations appear exhausted. Integrating immunologic and metabolic profiles during co-pathogen infection and malnutrition, we develop a working mechanistic model of how cumulative diet-induced and pathogen-triggered microbial perturbations result in an increasingly wasted host.

  14. Touching lips and hearing fingers: effector-specific congruency between tactile and auditory stimulation modulates N1 amplitude and alpha desynchronization.

    Science.gov (United States)

    Shen, Guannan; Meltzoff, Andrew N; Marshall, Peter J

    2018-01-01

    Understanding the interactions between audition and sensorimotor processes is of theoretical importance, particularly in relation to speech processing. Although one current focus in this area is on interactions between auditory perception and the motor system, there has been less research on connections between the auditory and somatosensory modalities. The current study takes a novel approach to this omission by examining specific auditory-tactile interactions in the context of speech and non-speech sound production. Electroencephalography was used to examine brain responses when participants were presented with speech syllables (a bilabial sound /pa/ and a non-labial sound /ka/) or finger-snapping sounds that were simultaneously paired with tactile stimulation of either the lower lip or the right middle finger. Analyses focused on the sensory-evoked N1 in the event-related potential and the extent of alpha band desynchronization elicited by the stimuli. N1 amplitude over fronto-central sites was significantly enhanced when the bilabial /pa/ sound was paired with tactile lip stimulation and when the finger-snapping sound was paired with tactile stimulation of the finger. Post-stimulus alpha desynchronization at central sites was also enhanced when the /pa/ sound was accompanied by tactile stimulation of the lip. These novel findings indicate that neural aspects of somatosensory-auditory interactions are influenced by the congruency between the location of the bodily touch and the bodily origin of a perceived sound.

  15. pKa modulation of the acid/base catalyst within GH32 and GH68: a role in substrate/inhibitor specificity?

    Directory of Open Access Journals (Sweden)

    Shuguang Yuan

    Full Text Available Glycoside hydrolases of families 32 (GH32 and 68 (GH68 belong to clan GH-J, containing hydrolytic enzymes (sucrose/fructans as donor substrates and fructosyltransferases (sucrose/fructans as donor and acceptor substrates. In GH32 members, some of the sugar substrates can also function as inhibitors, this regulatory aspect further adding to the complexity in enzyme functionalities within this family. Although 3D structural information becomes increasingly available within this clan and huge progress has been made on structure-function relationships, it is not clear why some sugars bind as inhibitors without being catalyzed. Conserved aspartate and glutamate residues are well known to act as nucleophile and acid/bases within this clan. Based on the available 3D structures of enzymes and enzyme-ligand complexes as well as docking simulations, we calculated the pKa of the acid-base before and after substrate binding. The obtained results strongly suggest that most GH-J members show an acid-base catalyst that is not sufficiently protonated before ligand entrance, while the acid-base can be fully protonated when a substrate, but not an inhibitor, enters the catalytic pocket. This provides a new mechanistic insight aiming at understanding the complex substrate and inhibitor specificities observed within the GH-J clan. Moreover, besides the effect of substrate entrance on its own, we strongly suggest that a highly conserved arginine residue (in the RDP motif rather than the previously proposed Tyr motif (not conserved provides the proton to increase the pKa of the acid-base catalyst.

  16. Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

    Science.gov (United States)

    Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

    2010-01-15

    Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

  17. Dual-specificity phosphatase 10 controls brown adipocyte differentiation by modulating the phosphorylation of p38 mitogen-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Hye-Ryung Choi

    Full Text Available Brown adipocytes play an important role in regulating the balance of energy, and as such, there is a strong correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism underlying white adipocyte differentiation has been well characterized, brown adipocyte differentiation has not been studied extensively. Here, we investigate the potential role of dual-specificity phosphatase 10 (DUSP10 in brown adipocyte differentiation using primary brown preadipocytes.The expression of DUSP10 increased continuously after the brown adipocyte differentiation of mouse primary brown preadipocytes, whereas the phosphorylation of p38 was significantly upregulated at an early stage of differentiation followed by steep downregulation. The overexpression of DUSP10 induced a decrease in the level of p38 phosphorylation, resulting in lower lipid accumulation than that in cells overexpressing the inactive mutant DUSP10. The expression levels of several brown adipocyte markers such as PGC-1α, UCP1, and PRDM16 were also significantly reduced upon the ectopic expression of DUSP10. Furthermore, decreased mitochondrial DNA content was detected in cells expressing DUSP10. The results obtained upon treatment with the p38 inhibitor, SB203580, clearly indicated that the phosphorylation of p38 at an early stage is important in brown adipocyte differentiation. The effect of the p38 inhibitor was partially recovered by DUSP10 knockdown using RNAi.These results suggest that p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38 phosphorylation at an early stage is critical in brown adipocyte differentiation. Thus, the regulation of DUSP10 activity affects the efficiency of brown adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the regulation of obesity.

  18. Association Between Substance Use and Gun-Related Behaviors.

    Science.gov (United States)

    Chen, Danhong; Wu, Li-Tzy

    2016-01-01

    Gun-related violence is a public health concern. This study synthesizes findings on associations between substance use and gun-related behaviors. Searches through PubMed, Embase, and PsycINFO located 66 studies published in English between 1992 and 2014. Most studies found a significant bivariate association between substance use and increased odds of gun-related behaviors. However, their association after adjustment was mixed, which could be attributed to a number of factors such as variations in definitions of substance use and gun activity, study design, sample demographics, and the specific covariates considered. Fewer studies identified a significant association between substance use and gun access/possession than other gun activities. The significant association between nonsubstance covariates (e.g., demographic covariates and other behavioral risk factors) and gun-related behaviors might have moderated the association between substance use and gun activities. Particularly, the strength of association between substance use and gun activities tended to reduce appreciably or to become nonsignificant after adjustment for mental disorders. Some studies indicated a positive association between the frequency of substance use and the odds of engaging in gun-related behaviors. Overall, the results suggest a need to consider substance use in research and prevention programs for gun-related violence. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Radioactive substance solidifying device

    International Nuclear Information System (INIS)

    Sakoda, Kotaro.

    1979-01-01

    Purpose: To easily solidify radioactive substances adhering to the surfaces of solid wastes without scattering in the circumference by paints, and further to reduce surface contamination concentrations. Constitution: Solid wastes are placed on a hanging plate, and dipped in paints within a paint dipping treatment tank installed at the lower part of a treatment tank by means of a monorail hoist, and the surfaces of said solid wastes are coated with paints, thereby to solidify the radioactivity on the surfaces of the solid wastes. After dipping, the solid wastes are suspended up to a paint spraying tank to dry the paints. After drying, non-contaminated paints are atomized to apply through an atomizing tube onto the solid wastes. After drying the atomized paints, the solid wastes are carried outside the treatment tank by means of the monorail hoist. (Yoshino, Y.)

  20. Substance P release from rat hypothalamus and spinal cord

    International Nuclear Information System (INIS)

    Kronheim, S.; Sheppard, M.C.; Pimstone, B.L.

    1980-01-01

    A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 μM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested

  1. Substance Use and Mental Health

    Science.gov (United States)

    ... and Alcohol Tobacco Learn More Substance Use and Mental Health Drugs and Alcohol Did you know that addiction ... Plus – also en Español Treatment Substance Abuse and Mental Health Administration (SAMHSA): SAMHSA’s National Helpline: 1-800-662- ...

  2. Role of parenting styles in adolescent substance use: results from a Swedish longitudinal cohort study

    Science.gov (United States)

    Berge, J; Sundell, K; Öjehagen, A; Håkansson, A

    2016-01-01

    Objective Adolescent substance use is an area of concern because early substance use is associated with a higher risk of adverse outcomes. Parenting style, defined as the general style of parenting, as well as substance-specific parenting practices may influence children's substance use behaviour. The present study aims to probe the impact of parenting style on adolescent substance use. Method A cohort of 1268 adolescents (48% girls), aged 12–13 years at baseline, from 21 junior high schools was assessed in the first semester of junior high school, and then again in the last semester of the 9th grade, 32 months later. Parenting style, operationalised as a fourfold classification of parenting styles, including established risk factors for adolescent substance use, were measured at baseline. Results Neglectful parenting style was associated with worse substance use outcomes across all substances. After adjusting for other proximal risk factors in multivariate analyses, parenting style was found to be unrelated to substance use outcomes with one exception: authoritative parenting style was associated with less frequent drinking. Association with deviant peers, delinquent behaviour, provision of alcohol by parents, and previous use of other substances were associated with substance use outcomes at follow-up. Conclusions The results of the present study indicate that parenting style may be less important for adolescent substance use outcomes than what has previously been assumed, and that association with deviant peers and delinquent behaviour may be more important for adolescent substance use outcomes than general parenting style. PMID:26769781

  3. Production of chemical substances in Tajikistan

    International Nuclear Information System (INIS)

    Boboev, Kh.E.; Nazarov, K.M.

    2010-01-01

    Full text: Government of the Republic of Tajikistan has signed Convention "On prohibition of chemical weapon application"and no chemical weapon (CHW) is produced on the territory of republic. However, the potential production of CHW by individual persons or groups can be organized, using available production and obtaining chemical substances from other countries. Chemical substances, which have strong damage effect, easily, can be synthesized in chemical laboratories. These are general toxic substances, as hydrocyanic acid acid, phosgene, mustard gas, lewisite, sarin and others. The similar chemical substances of industrial significance are produced in Tajikistan: ammonia, chlorine, explosives, caustic soda, carbamide, formaldehyde and others. For industrial needs and agriculture from other countries Tajikistan is receiving the following: sodium cyanide and potassium for gold-mining; mineral acids; pesticides and others. Besides, there are different deposits in Tajikistan, reprocessing of which gives an opportunity to obtain different chemical substances. What can be obtained from chemicals produced in Tajikistan? Chlorine - from this reagent the fluoride chlorine, phosgene COCl_2 and many other compounds are easily synthesized, which are CHW components. Obtained cyanic compounds for gold mining can be used as precursor for neuroparalytic action. A big amount of metallic aluminum is produced in the republic. The Al powder for rocket fuel can be obtained from it. Obtained from other countries pesticides are potential components for CHW creation. A strong control and account of pesticides use is necessary. It is extremely important to control materials, equipment and technologies which allow countries and separate groups to create weapons of mass destruction (WMD). The most important factor is goods identification. Firstly - inspection of external view, labeling, packing specifications, license availability and etc. Strong control of checklists is necessary according

  4. Neuroregulatory properties of substance P in the enteric nervous system

    International Nuclear Information System (INIS)

    Smith, K.E.

    1985-01-01

    Substance P (SP) is a putative neurotransmitter in both central and peripheral nervous systems. Its presence in intrinsic neurons of the gut, combined with its potent biological effects on this tissue, suggest that endogenous SP may play a role in the physiological regulation of gastrointestinal function. SP elicits potent, atropine-resistant contractions of guinea-pig ileum which mimic the effects of high-frequency electrical field stimulation. In addition, SP-like immunoreactivity was found to be released from segments of guinea-pig ileum in a calcium-dependent fashion by electrical stimulation. A SP radioligand binding assay was developed in order to characterize SP receptors in the rat gut. 3 H-SP binds with specificity and high-affinity to membranes of rat small intestine; Scatchard plots of saturation data are curved, indicating the presence of multiple binding sites. The K/sub D/ for the high-affinity site is 0.25 nM as determined by computerized non-linear least squares analysis. Specific binding is linear with protein, dependent on temperature, and reversible. The rate constants for association and dissociation of 0.5 nm 3 H-SP are: value derived form these constants, 0.34nM, agrees well with K/sub D/ derived from Scatchard plots. The rank order of potency for various tachykinins in inhibiting 3 H-SP binding indicates that the high-affinity site is a P-type tachykinin receptor. Specific 3 H-SP binding is modulated in a dose-related fashion by guanine nucleotides; a reduction in binding is seen which can be largely attributed to an increase in the rate of dissociation of 3 H-SP in the presence of GTP. This suggests that the binding site is a receptor linked to an effector system by a GTP-binding protein

  5. Intra-individual diagnostic image quality and organ-specific-radiation dose comparison between spiral cCT with iterative image reconstruction and z-axis automated tube current modulation and sequential cCT

    International Nuclear Information System (INIS)

    Wenz, Holger; Maros, Máté E.; Meyer, Mathias; Gawlitza, Joshua; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O.; Groden, Christoph; Henzler, Thomas

    2016-01-01

    •Superiority of spiral versus sequential cCT in image quality and organ-specific-radiation dose.•Spiral cCT: lower organ-specific-radiation-dose in eye lense compared to tilted sequential cCT.•State-of-the-art IR spiral cCT techniques has significant advantages over sequential cCT techniques. Superiority of spiral versus sequential cCT in image quality and organ-specific-radiation dose. Spiral cCT: lower organ-specific-radiation-dose in eye lense compared to tilted sequential cCT. State-of-the-art IR spiral cCT techniques has significant advantages over sequential cCT techniques. To prospectively evaluate image quality and organ-specific-radiation dose of spiral cranial CT (cCT) combined with automated tube current modulation (ATCM) and iterative image reconstruction (IR) in comparison to sequential tilted cCT reconstructed with filtered back projection (FBP) without ATCM. 31 patients with a previous performed tilted non-contrast enhanced sequential cCT aquisition on a 4-slice CT system with only FBP reconstruction and no ATCM were prospectively enrolled in this study for a clinical indicated cCT scan. All spiral cCT examinations were performed on a 3rd generation dual-source CT system using ATCM in z-axis direction. Images were reconstructed using both, FBP and IR (level 1–5). A Monte-Carlo-simulation-based analysis was used to compare organ-specific-radiation dose. Subjective image quality for various anatomic structures was evaluated using a 4-point Likert-scale and objective image quality was evaluated by comparing signal-to-noise ratios (SNR). Spiral cCT led to a significantly lower (p < 0.05) organ-specific-radiation dose in all targets including eye lense. Subjective image quality of spiral cCT datasets with an IR reconstruction level 5 was rated significantly higher compared to the sequential cCT acquisitions (p < 0.0001). Consecutive mean SNR was significantly higher in all spiral datasets (FBP, IR 1–5) when compared to sequential cCT with a mean

  6. The self-perceived survival ability and reproductive fitness (SPFit) theory of substance use disorders.

    Science.gov (United States)

    Newlin, David B

    2002-04-01

    A new theory of substance use disorders is proposed-the SPFit theory-that is based on evolutionary biology and adaptive systems. Self-perceived survival ability and reproductive fitness (SPFit) is proposed as a human psychobiological construct that prioritizes and organizes (i.e. motivates) behavior, but is highly vulnerable to temporary, artificial activation by drugs of abuse. Autoshaping/sign-tracking/feature positive phenomena are proposed to underlie the development of craving and expectations about drugs as the individual learns that abused drugs will easily and reliably inflate SPFit. The cortico-mesolimbic dopamine system and its modulating interconnections are viewed as the biological substrate of SPFit; it is proposed to be a survival and reproductive motivation system rather than a reward center or reward pathway. Finally, the concept of modularity of mind is applied to the SPFit construct. Although considerable empirical data are consistent with the theory, new research is needed to test specific hypotheses derived from SPFit theory.

  7. Maintenance and hazardous substances

    NARCIS (Netherlands)

    Kuhl, K.; Terwoert, J.; Cabecas, J.J.M.

    2012-01-01

    Maintenance workers come into close contact with a broad variety of often hazardous chemicals. Depending on the specific type, these chemicals may not only cause diseases like skin sores or cancer, but many of them are highly flammable and explosive. This e-facts focuses on the specific risks

  8. Distillation of bituminous substances

    Energy Technology Data Exchange (ETDEWEB)

    du Buisson, M A.B.B.

    1845-06-23

    New and improved methods are described for the distillation of bituminous schistus and other bituminous substances, as well as for the purification, rectification, and preparation necessary for the employment of the productions obtained by such distillation for various useful purposes. This invention consists, first, in the arrangement and construction of furnace or apparatus for the distillation of schistus, and (any) other bituminous rocks. This furnace is made of circular brick-work, and is provided with the requisite number of fires placed round the circumference. The retort is of a conical or funnel shape, and when ready for use, has the appearance of one inverted cone being placed within a larger cone, in such a manner as to leave a space between the two cones for the reception of the schistus. Both cones are capable of being closed at their apexes, and their mouths, which are placed upwards, are connected together, and hermetically closed by a flat ring. The flame draft is caused to impinge against the lower portion of the outer cone and ascending, turns over the upper edge and descends within the inner cone to the mouth of the chimney, which is placed in the interior, and as low as may be convenient. A third cone is so placed within the inner cone as to cause the flame draft, in its descent, to bind against the surface of the retort.

  9. Just say know: an examination of substance use disorders among older adults in gerontological and substance abuse journals.

    Science.gov (United States)

    Rosen, Daniel; Engel, Rafael J; Hunsaker, Amanda E; Engel, Yael; Detlefsen, Ellen Gay; Reynolds, Charles F

    2013-01-01

    This article examines the extent to which studies of alcohol abuse, illicit drug use, and prescription drug abuse among older adults appear in the leading gerontological and substance abuse journals. The authors reviewed articles published in the 10 social science gerontological journals and the 10 social science substance abuse journals with the highest 5-year impact factors in PubMed from 2000 to 2010. Articles were selected that presented original research on alcohol, substance, or prescription abuse with older adults aged 50 and older; and were identified through aging and substance abuse-related Medical Subject Headings and word searches of titles and abstracts (N = 634). Full text of each article was reviewed by the authors, and consensus determined inclusion in the final sample. Of the 19,953 articles published respectively in the top 10 gerontological and substance abuse journals, 181 articles met the inclusion criteria of reporting findings related to substance use disorders among older adults. Specifically, 0.9% (102 of 11,700) of articles from the top 10 gerontology journals and 1.0% (79 of 8,253) of articles from the top 10 substance abuse journals met the criteria. Most published articles addressed alcohol misuse/abuse or polysubstance abuse with few articles addressing illicit drug use or the misuse of prescription medications. Less than 1% of articles published in the 10 gerontology journals and the 10 substance abuse journals with the highest 5-year impact scores addressed substance abuse in older adults. Practitioners treating health and/or mental health problems are at a disadvantage in accurately identifying and treating these conditions in older adult populations without a proper understanding of the role of comorbid substance use disorders.

  10. A method and apparatus for preparing the storage of noxious substances, in particular radioactive substances

    International Nuclear Information System (INIS)

    1974-01-01

    The invention relates to the storage of radioactive substances. It deals with a method for storing a substance, in particular a noxious or radioactive substance, comprising trapping said substance in a solid substance by bombarding said solid substance with ions of the above substance, so that the latter reaches a certain concentration level in the solid substance. This is applicable to the storage of radioactive wastes [fr

  11. Frequency specific modulation of human somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Matteo eFeurra

    2011-02-01

    Full Text Available Oscillatory neuronal activities are commonly observed in response to sensory stimulation. However, their functional roles are still the subject of debate. One way to probe the roles of oscillatory neural activities is to deliver alternating current to the cortex at biologically relevant frequencies and examine whether such stimulation influences perception and cognition. In this study, we tested whether transcranial alternating current stimulation (tACS over the primary somatosensory cortex (SI could elicit tactile sensations in humans in a frequency dependent manner. We tested the effectiveness of tACS over SI at frequency bands ranging from 2 to 70 Hz. Our results show that stimulation in alpha (10-14 Hz and high gamma (52-70 Hz frequency range produces a tactile sensation in the contralateral hand. A weaker effect was also observed for beta (16-20 Hz stimulation. These findings highlight the frequency-dependency of effective tACS over SI with the effective frequencies corresponding to those observed in previous EEG/MEG studies of tactile perception. Our present study suggests that tACS could be used as a powerful online stimulation technique to reveal the causal roles of oscillatory brain activities.

  12. When acute-stage psychosis and substance use co-occur: differentiating substance-induced and primary psychotic disorders.

    Science.gov (United States)

    Caton, C L; Samet, S; Hasin, D S

    2000-09-01

    Substances such as alcohol, cocaine, amphetamine, and cannabis can produce psychotic reactions in individuals who are otherwise free of serious mental illness. However, persons with primary psychotic disorders, such as schizophrenia and bipolar disorder, who use these substances often present for treatment with signs and symptoms similar to those whose psychosis resulted from the use of drugs alone. While it is often difficult to distinguish substance-induced from primary psychoses, especially early in the course of treatment, this differential diagnosis has important implications for treatment planning. To help clinicians distinguish these two types of presentations, the authors first review the types of psychotic symptoms that can co-occur with substance use. They discuss the prevalence and patterns of substance use that have been found in patients with schizophrenia and other primary psychotic disorders and review the negative outcomes associated with substance use in this population. The prevalence of and types of symptoms and problems associated with psychotic symptoms that occur as a result of substance use alone are also reviewed. The authors describe assessment procedures for differentiating substance-induced and primary psychotic disorders. They stress the importance of accurately establishing the temporal relationship between the substance use and the onset and continuation of psychotic symptoms in making a differential diagnosis, as well as the importance of being familiar with the types of psychological symptoms that can occur with specific substances. The authors review the utility and limitations of a number of diagnostic instruments for assessing patients with co-occurring psychosis and substance use problems, including The Addiction Severity Index, The Michigan Alcohol Screening Test, and diagnostic interviews such as the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM. They then discuss the

  13. Alexithymia in Egyptian Substance Abusers.

    Science.gov (United States)

    El Rasheed, Amany Haroun

    2001-03-01

    Alexithymia is thought of as a trait that predisposes to drug abuse. Moreover, it is suggested to be related to type of the substance abused, with the worst-case scenario including a worse prognosis as well as tendency to relapse or even not to seek treatment at all. To address this important subject in Egyptian patients, a sample of 200 Egyptian substance abusers was randomly selected from inpatients in the Institute of Psychiatry, Ain Shams University, Egypt. The study also included 200 group-matched controls. DSM-IV criteria were used for assessment of substance use disorders, and toxicologic urine analysis was used to confirm the substances of abuse. Toronto Alexithymia Scale (TAS)-Arabic version was used for assessment of alexithymia. It was found that alexithymia was significantly more prevalent in the substance use disorders group as compared to healthy controls. It was also found that among the substance use disorders group, alexithymics reported more polysubstance abuse, more opiate use (other than heroin IV), lower numbers of hospitalizations, lower numbers of reported relapses, and a lower tendency to relapse as a result of internal cues compared to patients without alexithymia. Statistically significant associations were also found between alexithymia and more benzodiazepine abuse and nonpersistence in treatment. The results suggest that alexithymia should be targeted in a treatment setting for substance use disorders.

  14. Psychiatric comorbidity and acculturation stress among Puerto Rican substance abusers.

    Science.gov (United States)

    Conway, Kevin P; Swendsen, Joel D; Dierker, Lisa; Canino, Glorisa; Merikangas, Kathleen R

    2007-06-01

    Although acculturation to the United States has been associated with an increase in substance, mood, and anxiety disorders in Latino populations, few studies have examined this concept relative to comorbidity among these syndromes. This study compares the prevalence and patterns of psychiatric comorbidity among Puerto Ricans with substance use disorders living in San Juan (Puerto Rico) to those who have migrated to New Haven (Connecticut) and examines the association between acculturation-related stress and the prevalence and patterns of psychiatric comorbidity among those who have migrated to New Haven. Lifetime levels of nearly all comorbid psychiatric disorders among respondents with substance use disorders were generally similar across sites. However, the risk of any co-occurring psychiatric disorder was higher among substance use disorder cases in New Haven who reported high levels of total acculturation stress and family-specific acculturation stress. These findings were generally accounted for by associations between affective disorders and high scores on these indicators of acculturation stress. The overall prevalence and patterns of psychiatric comorbidity are remarkably similar among Puerto Rican substance abusers whether they live in San Juan or have migrated to New Haven, thereby demonstrating robustness to differences in geographic location. Nevertheless, the degree of acculturation-related family stress is positively associated with co-occurring substance and psychiatric disorders, particularly affective disorders. Intervention in family strain related to the acculturation process may diminish the development of comorbid mental disorders and assist in implementing successful treatment of substance abuse.

  15. Metal homeostasis in Hypogymnia physodes is controlled by lichen substances

    International Nuclear Information System (INIS)

    Hauck, Markus

    2008-01-01

    The hypothesis was tested that the lichen substances produced by the epiphytic lichen Hypogymnia physodes control the intracellular uptake of divalent transition metals. Incubating lichen thalli with and without their natural content of lichen substances with metal solutions showed that the lichen substances of H. physodes selectively inhibit the uptake of Cu 2+ and Mn 2+ , but not of Fe 2+ and Zn 2+ . Such behavior is ecologically beneficial, as ambient concentrations of Cu 2+ and Mn 2+ in precipitation and bark are known to limit the abundance of H. physodes, whereas limiting effects of Fe 2+ or Zn 2+ have never been found. This suggests that increasing the Cu 2+ and Mn 2+ tolerance stimulated the evolution of lichen substances in H. physodes. The depsidone physodalic acid is apparently most effective at reducing Cu 2+ and Mn 2+ uptake among the seven lichen substances produced by H. physodes. Probably lichen substances play a general role in the metal homeostasis of lichens. - Lichen substances in Hypogymnia physodes specifically reduce the uptake of Cu 2+ and Mn 2+ , but not Fe 2+ or Zn 2+

  16. Stroke And Substance Abuse

    Directory of Open Access Journals (Sweden)

    A Chitsaz

    2017-02-01

    Full Text Available Introduction: stroke in recreational substance users can be an indirect complication, like endocarditis and cardio embolism in parenteral drug users. With some drug like cocaine, stroke appear to be the result of a direct effect. In young subjects without other risk factors provide persuasive evidence for causality . OPIATES: Heroine is the most abused opiate drug, which is administered by injection, by snorting or by smoking. Stroke affects heroin users by diverse mechanisms,. Injectors are at risk of infections endocarditis, which carries risk for both ischemic and hemorrhagic stroke. Cerebral or subarachnoid hemorrhage usually occurs after rupture of a septic (mycotic aneurysm. Heroine users can are also at risk for hemorrhagic stroke secondary to liver failure with deranged clotting and to heroin nephropathy with uremia or malignant hypertension. In some heroin users the drug it self is directly causal due to vasculitis, hypersensitivity and immunologic changes. Embolization of foreign material to brain due to mixed of heroine with quinine can cause cerebral embolism. AMPHETAMINE AND other psychostimulants: In abuser of amphetamine hemorrhagic stroke can occur, oral, intravenous, nasal, and inhalational routes of administration have been reported. Most were chronic user, but in several patients, stroke followed a first exposure. Some of amphetamine induced intracranial hemorrhages are secondary to acute hypertension, some to cerebral vacuities, and some to a combination of two. Decongestants and diet pills: Phenylpropanolamine (PPA, an amphetamine – like drug, in decongestants and diet pills, induce acute hypertension, sever headache, psychiatric symptoms, seizures and hemorrhagic stroke. Ephedrine and pseudo ephedrine are present in decongestants and bronchodilators and induce headache, tachyarrhythmia, hypertensive emergency, and hemorrhagic and occlusive stroke. Ecstasy, 3,4 Methylenedioxymethamphetamin (MDMA with amphetamine like can

  17. Ozone-depleting Substances (ODS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global warming...

  18. Dermal uptake of petroleum substances

    NARCIS (Netherlands)

    Jakasa, Ivone; Kezic, Sanja; Boogaard, Peter J.

    2015-01-01

    Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount

  19. [Psychoactive substance use during pregnancy: a review].

    Science.gov (United States)

    Lamy, S; Thibaut, F

    2010-02-01

    these high-risk pregnancies. Environmental factors such as low economic status or marital status may play an important role. Personality disorders may also contribute to substance or alcohol use during pregnancy. In fact, in most studies the quality of the obstetrical survey is lower in pregnant women using drugs or alcohol but it remains difficult to describe a specific at-risk profile in these pregnant women. Consumption of alcohol or of one or more psychoactive substances during pregnancy may have serious consequences on the pregnancy and on the child's development. Fetal alcoholism syndrome is the main etiology of mental retardation in France. We need to improve our knowledge of alcohol and substance use during pregnancy in order to target information for prevention campaigns and to implement specific mother and child medical care in high-risk populations. Copyright (c) 2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  20. Area Specific Self-Esteem, Values, and Adolescent Substance Use

    Science.gov (United States)

    Donnelly, Joseph; Young, Michael; Pearson, Rebecca; Penhollow, Tina M.; Hernandez, Aida

    2008-01-01

    The use of illicit and licit drugs continues to be a major public health concern. Many prevention and drug education programs address this issue by attempting to enhance self-esteem. The idea is that increased levels of self-esteem will serve as a protective factor in decreasing the motivation and increasing the resistance to use drugs. This study…

  1. Second generation SLAC modulator

    International Nuclear Information System (INIS)

    Donaldson, A.R.; Cron, J.C.; Hanselman, R.R.

    1986-06-01

    The Stanford Linear Accelerator Laboratory has undertaken the construction of a single pass electron-positron collider. In order to reach required beam energy 235 new klystrons needed upgraded modulator systems. The collider will use 50 GeV electrons and positrons. The increase in accelerator energy from the present 30 GeV necessitates the replacement of existing 35 MW klystrons with new 67 MW units. The doubling of klystron output power required a redesign of the modulator system. The 67 MW klystron needs a 350 kV beam voltage pulse with a 3.7 μs pulse width. A new pulse transformer was designed to deliver the increased voltage and pulse width. Pulse cable design was evaluated to obtain increased reliability of that critical element. The modulator, with the exception of its power supply, was rebuilt to produce the required power increase while enhancing reliability and improving maintainability. An investigation of present thyratron switch tube performance under the new operating conditions resulted in agitation and some warranted panic but these conditions were mitigated after several successful experiments and some evolutionary narrowing of the klystron pulse width. The discussion will cover the upgraded modulator system specifications and some details of the new pulse transformer tank, pulse cable, modulator, and modulator switch tube

  2. The Web-based Module of Changes in Objects

    Science.gov (United States)

    Triayomi, R.

    2017-09-01

    To understand the changes of substances contained in such a kind of substance and substance characteristics then need a deep study of the concept. In this concept is expected to understand the changes of objects such as substance type and substance characteristics. Types of substances and characteristics of substances through physical changes and chemical changes and means of separation consisting of two or more substances. The principle of separation of the mixture is based on differences in physical properties of its constituents, such as substances, particle size, melting point, boiling point, magnetic properties, solubility, and so forth. This study aims to produce a web-based module of changes in objects that are valid, practical, and have effectiveness of student learning outcomes and activities on natural science learning. The experiment was conducted on 30 children in South Sumatera. The case of the development of the learning module of change of the object is influenced by the child’s understanding of the concept. Expected to be adapted by world teachers.

  3. Emotion, Decision-Making and Substance Dependence: A Somatic-Marker Model of Addiction

    Science.gov (United States)

    Verdejo-García, A; Pérez-García, M; Bechara, A

    2006-01-01

    Similar to patients with orbitofrontal cortex lesions, substance dependent individuals (SDI) show signs of impairments in decision-making, characterised by a tendency to choose the immediate reward at the expense of severe negative future consequences. The somatic-marker hypothesis proposes that decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between abnormalities in experiencing emotions in SDI, and their severe impairments in decision-making in real-life. Growing evidence from neuroscientific studies suggests that core aspects of substance addiction may be explained in terms of abnormal emotional guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in SDI. Combined neuropsychological and physiological assessment has demonstrated that the poorer decision-making of SDI is associated with altered reactions to reward and punishing events. Imaging studies have shown that impaired decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, including the ventromedial cortex, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker model of addiction. PMID:18615136

  4. Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: Implications for secondary cancer risk assessment

    International Nuclear Information System (INIS)

    Joosten, Andreas; Matzinger, Oscar; Jeanneret-Sozzi, Wendy; Bochud, François; Moeckli, Raphaël

    2013-01-01

    Background and purpose: To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS). Materials and methods: Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal + modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS. Results: Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4–5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses. Conclusions: In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart)

  5. Negative attributions towards people with substance use disorders in South Africa: Variation across substances and by gender

    Directory of Open Access Journals (Sweden)

    Sorsdahl Katherine

    2012-08-01

    Full Text Available Abstract Background Little research has examined attitudes towards people who use substances in low and middle income countries (LMIC. Therefore, the present study examined the attributions made by the general South African population about people who use substances and whether these attributions differ by the type of substance being used, the gender of the person using the substance, or the characteristics of the person making the attribution. Method A convenience sample of 868 members of the general public was obtained through street-intercept methods. One of 8 vignettes portraying alcohol, cannabis, methamphetamine or heroin, with either a male or female as the protagonist was presented to each respondent. Respondents’ attitudes towards the specific cases were investigated. Results Respondents held equally negative views of the presented substances, with the exception of the cannabis vignette which was considered significantly less “dangerous” than the alcohol vignette. Respondents were more likely to offer “help” to women who use alcohol, but more likely to suggest “coercion into treatment” for men. Individuals who scored higher on the ASSIST were more likely to hold negative attitudes towards substance users and black African respondents were more likely to offer help to individuals who use substances. Conclusion The stigma associated with substance use in South Africa is high and not necessarily dependent on the drug of choice. However, a range of factors, including gender of the substance user, and ethnicity of the rater, may impact on stigma. Interventions designed to strengthen mental health literacy and gender-focused anti-stigma campaigns may have the potential to increase treatment seeking behaviour.

  6. Irreducible Specht modules are signed Young modules

    OpenAIRE

    Hemmer, David J.

    2005-01-01

    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  7. Monetary rewards modulate inhibitory control

    Directory of Open Access Journals (Sweden)

    Paula Marcela Herrera

    2014-05-01

    Full Text Available The ability to override a dominant response, often referred to as behavioural inhibiton, is considered a key element of executive cognition. Poor behavioural inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioural inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/Nogo and Stop Signal Tasks. Several studies have reported a positive modulatory effect of reward on the performance of such tasks in pathological conditions such as substance abuse, pathological gambling, and ADHD. However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory paradigms are rare and consequently, little is known about the finer grained relationship between motivation and self-control. Here, we probed the effect of reward and reward magnitude on behavioural inhibition using two modified version of the widely used Stop Signal Task. The first task compared no reward with reward, whilst the other compared two different reward magnitudes. The reward magnitude effect was confirmed by the second study, whereas it was less compelling in the first study, possibly due to the effect of having no reward in some conditions. In addition, our results showed a kick start effect over global performance measures. More specifically, there was a long lasting improvement in performance throughout the task, when participants received the highest reward magnitudes at the beginning of the protocol. These results demonstrate that individuals’ behavioural inhibition capacities are dynamic not static because they are modulated by the reward magnitude and initial reward history of the task at hand.

  8. Adolescent brain cognitive development (ABCD study: Overview of substance use assessment methods

    Directory of Open Access Journals (Sweden)

    Krista M. Lisdahl

    2018-08-01

    Full Text Available One of the objectives of the Adolescent Brain Cognitive Development (ABCD Study (https://abcdstudy.org/ is to establish a national longitudinal cohort of 9 and 10 year olds that will be followed for 10 years in order to prospectively study the risk and protective factors influencing substance use and its consequences, examine the impact of substance use on neurocognitive, health and psychosocial outcomes, and to understand the relationship between substance use and psychopathology. This article provides an overview of the ABCD Study Substance Use Workgroup, provides the goals for the workgroup, rationale for the substance use battery, and includes details on the substance use module methods and measurement tools used during baseline, 6-month and 1-year follow-up assessment time-points. Prospective, longitudinal assessment of these substance use domains over a period of ten years in a nationwide sample of youth presents an unprecedented opportunity to further understand the timing and interactive relationships between substance use and neurocognitive, health, and psychopathology outcomes in youth living in the United States. Keywords: Adolescent Brain Cognitive Development Study, Adolescent, Child, Substance use, Alcohol, Cannabis, Marijuana, Nicotine, Longitudinal, Methods, Assessment, Drug use, Prescription drug use, Inhalants

  9. On staggered indecomposable Virasoro modules

    International Nuclear Information System (INIS)

    Kytoelae, Kalle; Ridout, David

    2009-01-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L 0 is assumed to be nondiagonalizable, possessing Jordan blocks of rank 2. Moreover, the module is further assumed to have a highest weight submodule, the 'left module', and that the quotient by this submodule yields another highest weight module, the 'right module'. Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centers on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension 0, 1, or 2, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulas as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit.

  10. On staggered indecomposable Virasoro modules

    Energy Technology Data Exchange (ETDEWEB)

    Kytoelae, Kalle [Geneve Univ. (Switzerland); Ridout, David [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-06-15

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be non-diagonalisable, possessing Jordan blocks of rank two. Moreover, the module is further assumed to have a highest weight submodule, the ''left module'', and that the quotient by this submodule yields another highest weight module, the ''right module''. Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centres on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension zero, one or two, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulae as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit. (orig.)

  11. On staggered indecomposable Virasoro modules

    International Nuclear Information System (INIS)

    Kytoelae, Kalle; Ridout, David

    2009-06-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be non-diagonalisable, possessing Jordan blocks of rank two. Moreover, the module is further assumed to have a highest weight submodule, the ''left module'', and that the quotient by this submodule yields another highest weight module, the ''right module''. Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centres on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension zero, one or two, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulae as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit. (orig.)

  12. On staggered indecomposable Virasoro modules

    Science.gov (United States)

    Kytölä, Kalle; Ridout, David

    2009-12-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be nondiagonalizable, possessing Jordan blocks of rank 2. Moreover, the module is further assumed to have a highest weight submodule, the "left module," and that the quotient by this submodule yields another highest weight module, the "right module." Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centers on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension 0, 1, or 2, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulas as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit.

  13. Impact of contextual factors and substance characteristics on perspectives toward cognitive enhancement.

    Directory of Open Access Journals (Sweden)

    Sebastian Sattler

    Full Text Available Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimentally and presented to respondents. Students in four German universities rated their willingness to use and moral acceptance of different substances for cognitive enhancement. We found that the overall willingness to use performance enhancing substances is low. Most respondents considered the use of these substances as morally unacceptable. Situational influences such as peer pressure, policies concerning substance use, relative performance level of peers, but also characteristics of the substance, such as perceptions of substance safety, shape the willingness and acceptability of using a substance to enhance academic performance. Among the findings is evidence of a contagion effect meaning that the willingness was higher when the respondents have more CE drug users in their social network. We also found deterrence effects from strong side effects of using the substance, as well as from policy regulations and sanctions. Regulations might activate social norms against usage and sanctions can be seen as costly to users. Moreover, enhancement substances seem to be most tempting to low performers to catch up with others compared to high performers. By identifying contextual factors and substance characteristics influencing the willingness and acceptability of cognitive enhancers, policy approaches could consider these insights to better manage the use of such substances.

  14. Impact of contextual factors and substance characteristics on perspectives toward cognitive enhancement.

    Science.gov (United States)

    Sattler, Sebastian; Forlini, Cynthia; Racine, Eric; Sauer, Carsten

    2013-01-01

    Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimentally and presented to respondents. Students in four German universities rated their willingness to use and moral acceptance of different substances for cognitive enhancement. We found that the overall willingness to use performance enhancing substances is low. Most respondents considered the use of these substances as morally unacceptable. Situational influences such as peer pressure, policies concerning substance use, relative performance level of peers, but also characteristics of the substance, such as perceptions of substance safety, shape the willingness and acceptability of using a substance to enhance academic performance. Among the findings is evidence of a contagion effect meaning that the willingness was higher when the respondents have more CE drug users in their social network. We also found deterrence effects from strong side effects of using the substance, as well as from policy regulations and sanctions. Regulations might activate social norms against usage and sanctions can be seen as costly to users. Moreover, enhancement substances seem to be most tempting to low performers to catch up with others compared to high performers. By identifying contextual factors and substance characteristics influencing the willingness and acceptability of cognitive enhancers, policy approaches could consider these insights to better manage the use of such substances.

  15. Perfluoroalkyl substances and fish consumption.

    Science.gov (United States)

    Christensen, Krista Y; Raymond, Michelle; Blackowicz, Michael; Liu, Yangyang; Thompson, Brooke A; Anderson, Henry A; Turyk, Mary

    2017-04-01

    Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. PFAS are emerging

  16. The soundtrack of substance use: music preference and adolescent smoking and drinking.

    Science.gov (United States)

    Mulder, Juul; Ter Bogt, Tom F M; Raaijmakers, Quinten A W; Gabhainn, Saoirse Nic; Monshouwer, Karin; Vollebergh, Wilma A M

    2009-01-01

    A connection between preferences for heavy metal, rap, reggae, electronic dance music, and substance use has previously been established. However, evidence as to the gender-specific links between substance use and a wider range of music genres in a nationally representative sample of adolescents has to date been missing. In 2003, the Dutch government funded the Dutch National School Survey on Substance Use (DNSSSU), a self-report questionnaire among a representative school-based sample of 7,324 adolescents aged 12 to 16 years, assessed music preference, tobacco, and alcohol use and a set of relevant covariates related to both substance use and music preference. Overall, when all other factors were controlled, punk/hardcore, techno/hardhouse, and reggae were associated with more substance use, while pop and classical music marked less substance use. While prior research showed that liking heavy metal and rap predicts substance use, in this study a preference for rap/hip-hop only indicated elevated smoking among girls, whereas heavy metal was associated with less smoking among boys and less drinking among girls. The types of music that mark increased substance use may vary historically and cross-culturally, but, in general, preferences for nonmainstream music are associated positively with substance use, and preferences for mainstream pop and types of music preferred by adults (classical music) mark less substance use among adolescents. As this is a correlational study no valid conclusions in the direction of causation of the music-substance use link can be drawn.

  17. Adolescent substance use in Israel: The roles of exposure to political traumas and posttraumatic stress symptoms.

    Science.gov (United States)

    Schiff, Miriam; Fang, Lin

    2014-06-01

    Previous studies have not examined the potential mediating role of posttraumatic stress symptoms (PTS) and moderating roles of gender and ethnicity among adolescents in the aftermath of political traumas, especially in the Middle East. This study of Israeli adolescents aimed to begin bridging these gaps in knowledge. We addressed the following hypotheses: (a) greater exposure to multiple political traumas would be associated with adolescent substance use; (b) greater PTS would be associated with adolescent substance use; (c) PTS would mediate the association of exposure to multiple political traumas on substance use; and (d) gender and ethnicity would moderate the pathways from exposure and PTS to substance use. A nationally representative sample included 4,733 Grade 10 and 11 students (half were females; 36.8% were Arabs). Results of bootstrapping estimations found a significant direct link between exposure to multiple political traumas and substance use, as well as an indirect link through PTS. Gender moderated the relationship between PTS and substance use, while ethnicity moderated the association between exposure and substance use. Specifically, female adolescent substance use decreased when their PTS increased. Arab adolescents who had greater exposure to multiple political traumas used more substances. PTS may be an important mechanism by which trauma exposure is associated with increased substance use. Screening adolescents for PTS and substance use, shortly after political trauma, is essential to address the potential risk factors in vulnerable adolescents.

  18. Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia.

    Science.gov (United States)

    Hartz, Sarah M; Horton, Amy C; Oehlert, Mary; Carey, Caitlin E; Agrawal, Arpana; Bogdan, Ryan; Chen, Li-Shiun; Hancock, Dana B; Johnson, Eric O; Pato, Carlos N; Pato, Michele T; Rice, John P; Bierut, Laura J

    2017-11-15

    There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity. We tested the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: the Collaborative Genetic Study of Nicotine Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317 control subjects). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to the 1000 Genomes reference panel. In each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo-R 2 range 0.8-3.7%; minimum p = 4 × 10 -23 ). These results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Humic substances in ground waters

    International Nuclear Information System (INIS)

    Paxeus, N.; Allard, B.; Olofsson, U.; Bengtsson, M.

    1986-01-01

    The presence of naturally occurring complexing agents that may enhance the migration of disposed radionuclikes and thus facilitate their uptake by plantsis a problem associated with the underground disposal of radioactive wastes in bedrock. The main purpose of this work is to characterized humic substances from ground water and compare them with humic substances from surface water. The humic materials isolated from ground waters of a borehole in Fjaellveden (Sweden) were characterized by elemental and functional group analyses. Spectroscopic properties, molecular weight distributions as well as acid-base properties of the fulvic and humic fractions were also studied. The ground water humic substances were found to be quite similar in many respects (but not identical) to the Swedish surface water humics concentrated from the Goeta River but appeared to be quite different from the American ground water humics from Biscayne Florida Aquifer or Laramie Fox-Hills in Colorado. The physico-chemical properties of the isolated humic materials are discussed

  20. Signed Young Modules and Simple Specht Modules

    OpenAIRE

    Danz, Susanne; Lim, Kay Jin

    2015-01-01

    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  1. Identification of a specific assembly of the G protein Golf as a critical and regulated module of dopamine and adenosine-activated cAMP pathways in the striatum

    Directory of Open Access Journals (Sweden)

    Denis eHervé

    2011-08-01

    Full Text Available In the principal neurons of striatum (medium spiny neurons, MSNs, cAMP pathway is primarily activated through the stimulation of dopamine D1 and adenosine A2A receptors, these receptors being mainly expressed in striatonigral and striatopallidal MSNs, respectively. Since cAMP signaling pathway could be altered in various physiological and pathological situations, including drug addiction and Parkinson’s disease, it is of crucial importance to identify the molecular components involved in the activation of this pathway. In MSNs, cAMP pathway activation is not dependent on the classical Gs GTP-binding protein but requires a specific G protein subunit heterotrimer containing Galpha-olf/beta2/gamma7 in particular association with adenylate cyclase type 5. This assembly forms an authentic functional signaling unit since loss of one of its members leads to defects of cAMP pathway activation in response to D1 or A2A receptor stimulation, inducing dramatic impairments of behavioral responses dependent on these receptors. Interestingly, D1 receptor-dependent cAMP signaling is modulated by the neuronal levels of Galpha-olf, indicating that Galpha-olf represents the rate-limiting step in this signaling cascade and could constitute a critical element for regulation of D1 receptor responses. In both Parkinsonian patients and several animal models of Parkinson’s disease, the lesion of dopamine neurons produces a prolonged elevation of Galpha-olf levels. This observation gives an explanation for the cAMP pathway hypersensitivity to D1 stimulation, occurring despite an unaltered D1 receptor density. In conclusion, alterations in the highly specialized assembly of Galpha-olf/beta2/gamma7 subunits can happen in pathological conditions, such as Parkinson’s disease, and it could have important functional consequences in relation to changes in D1 receptor signaling in the striatum.

  2. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive

  3. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper

    2016-01-01

    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...

  4. Process of treating carbonaceous substances

    Energy Technology Data Exchange (ETDEWEB)

    1938-12-16

    A process is described of removing halogens or halogen compounds (or both) from the products which form when carbonaceous substances are treated thermally in the presence of halogens or halogen compounds, consisting of passing the reaction products at the same temperature with a substance able to fix halogens or acid halides through an apparatus included between the receiver and the heat exchanger, which contains, in a relatively restricted space, internal elements obliquely disposed in relation to the direction of the flow, stretched in this direction and constituted preferably of helicoidal passages.

  5. Measuring Peer Socialization for Adolescent Substance Use: A Comparison of Perceived and Actual Friends’ Substance Use Effects

    Science.gov (United States)

    Deutsch, Arielle R.; Chernyavskiy, Pavel; Steinley, Douglas; Slutske, Wendy S.

    2015-01-01

    Objective: There has been an increase in the use of social network analysis in studies of peer socialization effects on adolescent substance use. Some researchers argue that social network analyses provide more accurate measures of peer substance use, that the alternate strategy of assessing perceptions of friends’ drug use is biased, and that perceptions of peer use and actual peer use represent different constructs. However, there has been little research directly comparing the two effects, and little is known about the extent to which the measures differ in the magnitude of their influence on adolescent substance use, as well as how these two effects may be redundant or separate constructs. Method: Using Waves I and II of the National Longitudinal Study of Adolescent Health (Add Health) saturated subsample, we directly compared effects of perception of friends’ use (PFU) and actual friends’ use (AFU) on alcohol, cigarette, and marijuana initiation and persistence of use 1 year later. We also examined potential moderating effects of friendship quality and individual use on the relationship between perceived and actual friends’ substance use and outcomes. Results: Results indicated that, overall, PFU effects were larger than AFU effects; however, these effects did not significantly differ in magnitude for most models. In addition, interaction effects differed for different substances and usage outcomes, indicating the meaning of PFU and AFU constructs (and thus, different types of peer socialization) may change based on substance and type of use. Conclusions: These results highlight the multifaceted nature of peer influence on substance use and the importance of assessing multiple aspects of peer socialization while accounting for distinct contexts related to specific substances and use outcomes. PMID:25785802

  6. Workplace Substance-Use Norms as Predictors of Employee Substance Use and Impairment: A Survey of U.S. Workers*

    Science.gov (United States)

    Frone, Michael R.; Brown, Amy L.

    2010-01-01

    Objective: Although much research has explored the relation of substance-use norms to substance use among college students, much less research has focused on employed adults and the workplace as a social context for social norms regarding substance use. This study explored the relation of descriptive and injunctive workplace substance-use norms regarding alcohol and illicit drug use to employee substance use. Both alcohol use and illicit drug use were explored, as well as overall and context-specific use and impairment. Method: Data were collected from a national probability sample of 2,430 employed adults (55% female) using a random-digit-dial telephone survey. Overall employee alcohol and illicit drug use were assessed, as well as use before work, use and impairment during the workday, and use after work. Results: After controlling for a number of potential covariates, injunctive norms regarding workplace alcohol and illicit drug use predicted substance use and impairment overall and across all contexts of use. Descriptive norms predicted alcohol and illicit drug use before and during work, as well as workplace impairment. Conclusions: This study shows that both workplace injunctive and descriptive norms are important predictors of substance use in the U.S. workforce. There were two general patterns, however, that were consistent across both alcohol and illicit drug use. Social norms marketing campaigns, therefore, may be a useful way for employers to target employee substance use. The present results also helped to integrate the results of several prior studies that employed narrower samples and measures. PMID:20553660

  7. Cross-boundary substance uses among Hong Kong Chinese young adults.

    Science.gov (United States)

    Lau, Joseph T F; Tsui, Hi Yi; Lam, Lawrence T; Lau, Mason

    2007-09-01

    The study documents the characteristics of Hong Kong residents who used substances in mainland China. Characteristics of such users were compared with those using substances elsewhere. A cross-sectional survey was used. Data analyses were stratified by gender, and multivariate analyses were performed. Respondents, Hong Kong adults aged 18-30 (n = 6,528), were interviewed using a mixed interviewer and computerized mobile phone method, at the Hong Kong-mainland China boundary. Cross-border substance users and other types of substance users had characteristics that were quite different (e.g., education level, perceived harmfulness of substance use in general, having friends who frequently used substances in mainland China). Cross-boundary substance users also found it easier to obtain substances in mainland China than in Hong Kong (males: 60.5%, females: 39.6%) and perceived no chance of being arrested in mainland China because of substance use (men: 28.8%, women: 24.5%). They tended to use substances in discos/rave parties together with friends (men: 77%, women: 81%), and substances were often obtained for free (men: 63.2%, women: 78%). Ecstasy and ketamine were often used (men: 86.5% & 79.4%, women: 81% & 70.2%), and multiple uses of different substances were common (men: 81.3%, women: 68.6%). Lower price, peer influence, and better availability were reasons behind cross-boundary substance use behaviors. Cross-boundary substance users have specific characteristics. Prevention policies should take these characteristics into account. Regional collaborations are highly warranted.

  8. 9 CFR 73.10 - Permitted dips; substances allowed.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Permitted dips; substances allowed. 73.10 Section 73.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... flowers of sulphur or sulphur flour to 100 gallons of water; or a specifically permitted proprietary brand...

  9. Dating Violence and Substance Use among Ethnically Diverse Adolescents

    Science.gov (United States)

    Temple, Jeff R.; Freeman, Daniel H., Jr.

    2011-01-01

    Teen dating violence is a serious public health concern with numerous and long-lasting consequences. Although alcohol and drug use have been associated with dating violence, little is known about the role of specific substances, especially the use of club drugs and the nonmedical use of prescription drugs. Thus, the authors examined the…

  10. Substance Abuse and the Family.

    Science.gov (United States)

    Murphy, John P.

    1984-01-01

    Examines the effect that a substance abuser may have on the family system and the maladaptive roles sometimes assumed by family members. Discusses dysfunctional family phases and therapeutic issues and presents 11 guidelines for counselors working with chemically dependent families. (JAC)

  11. Substance Use as Impression Management.

    Science.gov (United States)

    Sharp, Mark J.; Getz, J. Greg

    1996-01-01

    Examines the function of substance use as an impression management tactic. Introductory psychology students (n=377) responded to a survey instrument measuring self-monitoring, perceived success in impression management, interaction anxiety, and self-esteem. Results suggest that alcohol use may serve an impression management function. (JPS)

  12. Substance Use among Welfare Recipients: Trends and Policy Responses. JCPR Working Paper.

    Science.gov (United States)

    Pollack, Harold A.; Danziger, Sheldon; Seefeldt, Kristin S.; Jayakody, Rukmalie

    Substance use by welfare recipients is frequently mentioned as an important barrier to well-being and social performance. This article uses nationally representative cross-sectional data and Michigan-specific panel data to summarize trends in substance use among Aid to Families with Dependent Children (AFDC) and Temporary Assistance to Needy…

  13. Paths Leading to Teenage Psychiatric Symptoms and Substance Use: Developmental Epidemiological Studies in Woodlawn.

    Science.gov (United States)

    Kellam, Sheppard G.; And Others

    Early predictors of two major areas of teenage outcome -- substance use and psychiatric symptoms -- were analyzed and specific developmental paths leading to each teenage outcome were identified in this long-term, follow-up study. Substance "use" rather than "abuse" and psychiatric "symptoms" rather than…

  14. Addressing Viral Hepatitis in People with Substance Use Disorders. Treatment Improvement Protocol (TIP) Series 53

    Science.gov (United States)

    Substance Abuse and Mental Health Services Administration, 2011

    2011-01-01

    Treatment Improvement Protocols (TIPs) are developed by the Center for Substance Abuse Treatment (CSAT), part of the Substance Abuse and Mental Health Services Administration (SAMHSA) within the U.S. Department of Health and Human Services (HHS). Each TIP involves the development of topic-specific best-practice guidelines for the prevention and…

  15. Influence of Conduct Problems and Depressive Symptomatology on Adolescent Substance Use: Developmentally Proximal versus Distal Effects

    Science.gov (United States)

    Maslowsky, Julie; Schulenberg, John E.; Zucker, Robert A.

    2014-01-01

    The identification of developmentally specific windows at which key predictors of adolescent substance use are most influential is a crucial task for informing the design of appropriately targeted substance use prevention and intervention programs. The current study examined effects of conduct problems and depressive symptomatology on changes in…

  16. 77 FR 42990 - Significant New Use Rules on Certain Chemical Substances

    Science.gov (United States)

    2012-07-23

    ... Pigment Manufacturers Association (CPMA) members with similar products, there is no substantiation of... the PMN substances have been incorporated into a polymer, glass, dispersion, cementitious matrix, or a.... Specifically, the PMN substances are intended to replace pigments containing heavy metals such as lead and...

  17. A survey on the presence of undesirable botanical substances in feed in the European Union

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Vancutsem, J.; Jorgensen, J.S.

    2009-01-01

    Directive 2002/32/EC of the European Parliament and of the Council of 7 May 2002 on undesirable substances in animal feed lists a range of substances from botanical origin (weed seeds) and additionally some chemical compounds directly originating from specific weeds. In order to examine the actual

  18. Adolescent substance use behavior and suicidal behavior for boys and girls: a cross-sectional study by latent analysis approach.

    Science.gov (United States)

    Wang, Peng-Wei; Yen, Cheng-Fang

    2017-12-08

    Adolescent suicidal behavior may consist of different symptoms, including suicidal ideation, suicidal planning and suicidal attempts. Adolescent substance use behavior may contribute to adolescent suicidal behavior. However, research on the relationships between specific substance use and individual suicidal behavior is insufficient, as adolescents may not use only one substance or develop only one facet of suicidal behavior. Latent variables permit us to describe the relationships between clusters of related behaviors more accurately than studying the relationships between specific behaviors. Thus, the aim of this study was to explore how adolescent substance use behavior contributes to suicidal behavior using latent variables representing adolescent suicidal and substance use behaviors. A total of 13,985 adolescents were recruited using a stratified random sampling strategy. The participants indicated whether they had experienced suicidal ideation, planning and attempts and reported their cigarette, alcohol, ketamine and MDMA use during the past year. Latent analysis was used to examine the relationship between substance use and suicidal behavior. Adolescents who used any one of the above substances exhibited more suicidal behavior. The results of latent variables analysis revealed that adolescent substance use contributed to suicidal behavior and that boys exhibited more severe substance use behavior than girls. However, there was no gender difference in the association between substance use and suicidal behavior. Substance use behavior in adolescents is related to more suicidal behavior. In addition, the contribution of substance use to suicidal behavior does not differ between genders.

  19. The intersecting roles of violence, gender, and substance use in the emergency department: a research agenda.

    Science.gov (United States)

    Choo, Esther K; Benz, Madeline; Rybarczyk, Megan; Broderick, Kerry; Linden, Judith; Boudreaux, Edwin D; Ranney, Megan L

    2014-12-01

    The relationship between gender, violence, and substance use in the emergency department (ED) is complex. This article examines the role of gender in the intersection of substance use and three types of violence: peer violence, intimate partner violence, and firearm violence. Current approaches to treatment of substance abuse and violence are similar across both genders; however, as patterns of violence and substance abuse differ by gender, interventions may be more effective if they are designed with a specific gender focus. © 2014 by the Society for Academic Emergency Medicine.

  20. Assessing Change in Psychosocial Functioning of Incarcerated Girls with a Substance Use Disorder: Gender Sensitive Substance Abuse Intervention

    Science.gov (United States)

    Roberts-Lewis, Amelia C.; Welch-Brewer, Chiquitia L.; Jackson, Mary S.; Kirk, Raymond; Pharr, O. Martin

    2010-01-01

    The objective of this preliminary study was to determine the effectiveness of a female gender-specific substance abuse treatment intervention (Holistic Enrichment for At-Risk Teens, or HEART) in improving problems related to personal and social functioning. A quasi-experimental, 2-group pretest and posttest repeated measures design was used to…

  1. Substance use by Egyptian youth: current patterns and potential avenues for prevention.

    Science.gov (United States)

    Loffredo, Christopher A; Boulos, Dina N K; Saleh, Doa'a A; Jillson, Irene A; Garas, Magdy; Loza, Nasser; Samuel, Philip; Shaker, Yousri Edward; Ostrowski, Mar-Jan; Amr, Sania

    2015-04-01

    Substance abuse in Egypt is a serious public health threat. Recent studies have demonstrated increases in the prevalence of the use of tobacco, illegal drugs, and over-the-counter drugs, particularly among youth. We conducted focus groups with a total of 40 male and female youth participants, ages 12-14 and 15-18, recruited from two different areas (Cairo and Alexandria) in 2012. We investigated their knowledge and perceptions regarding current substance use, its sources, and promoting and protecting factors, broadly addressing the use of tobacco products, illicit and prescription drugs, inhaled substances such as glue and solvents, and alcohol. Our findings suggest that: (1) youth in Egypt had access to and were actively using substances encountered in similar research worldwide, including tobacco, alcohol, illicit drugs, glue sniffing, and pharmaceutical agents; (2) smoking cigarettes and using hashish were the most common practices, and Tramadol was the most commonly used pharmaceutical drug; (3) peer pressure from friends stood out as the most common reason to start and continue using substances, followed by adverse life events and having a parent or family member who used substances; (4) strict parenting, religiosity, and having non-user friends were among the factors perceived by youth to prevent substance use or help them quit using substances; (5) most youths were aware of the adverse health effects of substance use. These findings will inform the design of quantitative surveys aimed at estimating the prevalence of specific behaviors related to substance use among youth and potential avenues for prevention.

  2. **1**5N-NMR INVESTIGATION OF HYDROXYLAMINE DERIVATIZED HUMIC SUBSTANCES.

    Science.gov (United States)

    Thorn, Kevin A.; Arterburn, Jeffrey B.; Mikita, Michael A.

    1986-01-01

    Humic substances are the most abundant naturally occurring refactory organic compounds in soils and water. They have a broad range of physical, chemical and physiological properties. In soils, humic substances contribute to the cation exchange capacity, help maintain the physical structure, and play a role in plant growth and nutrition. In aquatic systems, humic substances serve to regulate the levels of inorganic constituents, yield trihalomethanes upon chlorination, and transport or concentrate organic and inorganic pollutants. The oxygen containing functional groups of humic and fulvic acids are believed to play a key role in the chemical properties of humic substances. This study was undertaken to gain additional information on the specific types of oxygen functionalities in humic substances. Since the analysis of hydroxyl moieties had been earlier established, we focused our attention on the analysis of ketone and aldehyde functional groups in humic substances.

  3. Thermal management, systems and modules; Thermomanagement, Systeme und Module

    Energy Technology Data Exchange (ETDEWEB)

    Flik, M. [Behr GmbH und Co., Stuttgart (Germany)

    1999-11-01

    Up till now the individual systems for engine temperature control and air conditioning of the vehicle cabin have to a large extent been viewed independently of one another. With the progress of electronic control systems, however, Behr has adopted an integrative approach to managing all heat and substance flows outside of the engine. This perspective, which is known as thermal management, has significantly boosted the rate of innovation. In a short period of time, new and optimized modules and systems have allowed considerable improvements to be made in relation to passenger comfort and safety, the integration of subsystems and modules into the vehicle and environmental compatibility. This innovation drive, which also extends to the design of major modules, will continue to gain impetus in the future. (orig.) [German] Bisher wurden die verschiedenen Systeme zur Temperierung des Motors und zur Klimatisierung der Fahrzeugkabine weitgehend unabhaengig voneinander betrachtet. Mit dem Vordringen der elektronischen Regelung hat bei Behr jedoch eine gesamtheitliche Betrachtung aller Waerme- und Stoffstroeme ausserhalb des Motors eingesetzt. Diese Sichtweise, Thermomanagement genannt, hat eine erhebliche Innovationsdynamik ermoeglicht. Mit neuen und optimierten Modulen und Systemen konnten in kurzer Zeit betraechtliche Verbesserungen erzielt werden - bei Komfort und Sicherheit der Fahrzeuginsassen, bei der Integration der Subsysteme und Module ins Fahrzeug sowie bei seiner oekologischen Vertraeglichkeit. Diese Innovationsdynamik, die auch die Bildung von Grossmodulen einschliesst, wird in Zukunft noch zunehmen. (orig.)

  4. PETRORISK: a risk assessment framework for petroleum substances.

    Science.gov (United States)

    Redman, Aaron D; Parkerton, Thomas F; Comber, Mike H I; Paumen, Miriam Leon; Eadsforth, Charles V; Dmytrasz, Bhodan; King, Duncan; Warren, Christopher S; den Haan, Klaas; Djemel, Nadia

    2014-07-01

    PETRORISK is a modeling framework used to evaluate environmental risk of petroleum substances and human exposure through these routes due to emissions under typical use conditions as required by the European regulation for the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Petroleum substances are often complex substances comprised of hundreds to thousands of individual hydrocarbons. The physicochemical, fate, and effects properties of the individual constituents within a petroleum substance can vary over several orders of magnitude, complicating risk assessment. PETRORISK combines the risk assessment strategies used on single chemicals with the hydrocarbon block approach to model complex substances. Blocks are usually defined by available analytical characterization data on substances that are expressed in terms of mass fractions for different structural chemical classes that are specified as a function of C number or boiling point range. The physicochemical and degradation properties of the blocks are determined by the properties of representative constituents in that block. Emissions and predicted exposure concentrations (PEC) are then modeled using mass-weighted individual representative constituents. Overall risk for various environmental compartments at the regional and local level is evaluated by comparing the PECs for individual representative constituents to corresponding predicted no-effect concentrations (PNEC) derived using the Target Lipid Model. Risks to human health are evaluated using the overall predicted human dose resulting from multimedia environmental exposure to a substance-specific derived no-effect level (DNEL). A case study is provided to illustrate how this modeling approach has been applied to assess the risks of kerosene manufacture and use as a fuel. © 2014 SETAC.

  5. NEIGHBORHOOD NORMS AND SUBSTANCE USE AMONG TEENS

    Science.gov (United States)

    Musick, Kelly; Seltzer, Judith A.; Schwartz, Christine R.

    2008-01-01

    This paper uses new data from the Los Angeles Family and Neighborhood Survey (L.A. FANS) to examine how neighborhood norms shape teenagers’ substance use. Specifically, it takes advantage of clustered data at the neighborhood level to relate adult neighbors’ attitudes and behavior with respect to smoking, drinking, and drugs, which we treat as norms, to teenagers’ own smoking, drinking, and drug use. We use hierarchical linear models to account for parents’ attitudes and behavior and other characteristics of individuals and families. We also investigate how the association between neighborhood norms and teen behavior depends on: (1) the strength of norms, as measured by consensus in neighbors’ attitudes and conformity in their behavior; (2) the willingness and ability of neighbors to enforce norms, for instance, by monitoring teens’ activities; and (3) the degree to which teens are exposed to their neighbors. We find little association between neighborhood norms and teen substance use, regardless of how we condition the relationship. We discuss possible theoretical and methodological explanations for this finding. PMID:18496598

  6. ORIGINAL ARTICLES An epidemiological perspective of substance ...

    African Journals Online (AJOL)

    2002-09-06

    Sep 6, 2002 ... advertising linking alcohol with the glamour of sport. This inculcates values that ... of substance use is a useful preventive strategy, hence the importance of ... substance use and associated factors (including age, gender,.

  7. Dual Diagnosis: Substance Abuse and Mental Illness

    Science.gov (United States)

    ... is a term for when someone experiences a mental illness and a substance use disorder simultaneously. Either disorder—substance use or mental illness—can develop first. People experiencing a mental health ...

  8. EPA Linked Open Data: Substance Registry Service

    Data.gov (United States)

    U.S. Environmental Protection Agency — Substance Registry Services (SRS) is the Environmental Protection Agency's (EPA) central system for information about substances that are tracked or regulated by EPA...

  9. Agency for Toxic Substances and Disease Registry

    Science.gov (United States)

    ... Z # Search Form Controls Search The CDC submit Agency for Toxic Substances and Disease Registry Note: Javascript ... gov . Recommend on Facebook Tweet Share Compartir The Agency for Toxic Substances and Disease Registry (ATSDR) , based ...

  10. Dietary supplements containing prohibited substances

    African Journals Online (AJOL)

    with information regarding dietary supplements and be advised to minimise risks for ... to promote strength and muscle mass, ... selective oestrogen receptor modulators or .... It has also come to the attention of the WADA that another sub-.

  11. Role of parenting styles in adolescent substance use: results from a Swedish longitudinal cohort study.

    Science.gov (United States)

    Berge, J; Sundell, K; Öjehagen, A; Håkansson, A

    2016-01-14

    Adolescent substance use is an area of concern because early substance use is associated with a higher risk of adverse outcomes. Parenting style, defined as the general style of parenting, as well as substance-specific parenting practices may influence children's substance use behaviour. The present study aims to probe the impact of parenting style on adolescent substance use. A cohort of 1268 adolescents (48% girls), aged 12-13 years at baseline, from 21 junior high schools was assessed in the first semester of junior high school, and then again in the last semester of the 9th grade, 32 months later. Parenting style, operationalised as a fourfold classification of parenting styles, including established risk factors for adolescent substance use, were measured at baseline. Neglectful parenting style was associated with worse substance use outcomes across all substances. After adjusting for other proximal risk factors in multivariate analyses, parenting style was found to be unrelated to substance use outcomes with one exception: authoritative parenting style was associated with less frequent drinking. Association with deviant peers, delinquent behaviour, provision of alcohol by parents, and previous use of other substances were associated with substance use outcomes at follow-up. The results of the present study indicate that parenting style may be less important for adolescent substance use outcomes than what has previously been assumed, and that association with deviant peers and delinquent behaviour may be more important for adolescent substance use outcomes than general parenting style. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Illicit substance use among adolescents: a matrix of prospective predictors.

    Science.gov (United States)

    Petraitis, J; Flay, B R; Miller, T Q; Torpy, E J; Greiner, B

    1998-11-01

    This paper reviews findings from 58 prospective studies of illicit substance use (ISU) among adolescents. It arranges 384 findings according to three types of influence (viz., social, attitudinal, and intrapersonal) and four levels of influence (viz., ultimate, distal, proximal, and immediate). The bulk of evidence reconfirms the importance of several predictors of ISU (e.g., intentions and prior substance-related behavior, friendship patterns and peer behaviors, absence of supportive parents, psychological temperament), reveals that a few variables thought to be well-established predictors may not be (e.g., parental behaviors, parental permissiveness, depression, low self-esteem), and uncovers several variables where findings were either sparse or inconsistent (e.g., the role of public policies concerning ISU, mass media depictions of ISU, certain parenting styles, affective states, perceptions of parental disapproval for ISU, and substance-specific refusal skills). Directions for future research are discussed.

  13. Risk assessment of flavouring substances used in foods

    DEFF Research Database (Denmark)

    Norby, Karin; Beltoft, Vibe Meister; Greve, Krestine

    2006-01-01

    not to present a safety concern, have been specified. In the project a very comprehensive database (the FLAVIS database) has been developed for the evaluation. It compiles information on the about 2800 flavouring substances used in Europe: specifications, structural class, food categories used in, intake data......The aim of the present project, the FLAVIS project, is to perform risk assessment of chemically defined flavouring substances. The evaluations are then presented to the European Food Safety Authority (EFSA) for final adoption in its Scientific Panel on food additives, flavourings, processing aids...... and materials in contact with food. The regulatory background for the work is found in the European Parliament and Council Regulation No. 2232/96 laying down a procedure for the establishment of a list of flavouring substances the use of which will be authorised to the exclusion of all others in the EU...

  14. Abortion Legalization and Adolescent Substance Use

    OpenAIRE

    Charles, Kerwin Kofi; Stephens, Melvin, Jr

    2006-01-01

    We assess whether in utero exposure to legalized abortion in the early 1970's affected individuals' propensities to use controlled substances as adolescents. We exploit the fact that some states legalized abortion before national legalization in 1973 to compare differences in substance use for adolescents across birth cohorts in different states. We find that persons exposed to early legalization were, on average, much less likely to use controlled substances. We also assess how substance use...

  15. Psychotropic substances in indoor environments.

    Science.gov (United States)

    Cecinato, Angelo; Romagnoli, Paola; Perilli, Mattia; Patriarca, Claudia; Balducci, Catia

    2014-10-01

    The presence of drugs in outdoor air has been established, but few investigations have been conducted indoors. This study focused on psychotropic substances (PSs) at three schools, four homes and one office in Rome, Italy. The indoor drug concentrations and the relationships with the outdoor atmosphere were investigated. The optimised monitoring procedure allowed for the determination of cocaine, cannabinoids and particulate fractions of nicotine and caffeine. In-field experiments were performed during the winter, spring and summer seasons. Psychotropic substances were observed in all indoor locations. The indoor concentrations often exceeded those recorded both outdoors at the same sites and at the atmospheric pollution control network stations, indicating that the drugs were released into the air at the inside sites or were more persistent. During winter, the relative concentrations of cannabinol, cannabidiol and tetrahydrocannabinol depended on site and indoor/outdoor location at the site. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. US ITER limiter module design

    International Nuclear Information System (INIS)

    Mattas, R.F.; Billone, M.; Hassanein, A.

    1996-08-01

    The recent U.S. effort on the ITER (International Thermonuclear Experimental Reactor) shield has been focused on the limiter module design. This is a multi-disciplinary effort that covers design layout, fabrication, thermal hydraulics, materials evaluation, thermo- mechanical response, and predicted response during off-normal events. The results of design analyses are presented. Conclusions and recommendations are also presented concerning, the capability of the limiter modules to meet performance goals and to be fabricated within design specifications using existing technology

  17. TOXICOLOGICAL ENDPOINTS OF DOPING SUBSTANCES

    OpenAIRE

    BASARAN, A. Ahmet

    2018-01-01

    Athletes and non athletes weighlifters have tried to gain an unfairadvantage through the use doping substances since ancient times. Dopingsubstances although enhance sports performance, represent a risk to the healthof individuals and violate the sprit of competition. The use of prohibitedperformance enhancing drugs (PED’s) or methods to improve results incompetitive sports is referred as doping. Among the PED’s used areandrogenic-anabolic steroids (AASs), diuretics and masking agents, narkot...

  18. The administration of radioactive substances

    International Nuclear Information System (INIS)

    Bourdillon, P.J.; Godfrey, B.E.; O'Brien, R.

    1983-01-01

    A brief history is given of the evolution of a system to approve the licensing of doctors and dentists to use radioactive medicinal products in man. Currently, the Administration of Radioactive Substances Advisory Committee (ARSAC) is appointed by UK Health Ministers to advise them on the granting, renewal, suspension, revocation and variation of certificates. The type of information requested on the application form for a certificate is outlined. (UK)

  19. Personal networks of women in residential and outpatient substance abuse treatment.

    Science.gov (United States)

    Kim, HyunSoo; Tracy, Elizabeth; Brown, Suzanne; Jun, MinKyoung; Park, Hyunyong; Min, Meeyoung; McCarty, Chris

    This study compared compositional, social support, and structural characteristics of personal networks among women in residential (RT) and intensive outpatient (IOP) substance abuse treatment. The study sample included 377 women from inner-city substance use disorder treatment facilities. Respondents were asked about 25 personal network members known within the past 6 months, characteristics of each (relationship, substance use, types of support), and relationships between each network member. Differences between RT women and IOP women in personal network characteristics were identified using Chi-square and t -tests. Compared to IOP women, RT women had more substance users in their networks, more network members with whom they had used substances and fewer network members who provided social support. These findings suggest that women in residential treatment have specific network characteristics, not experienced by women in IOP, which may make them more vulnerable to relapse; they may therefore require interventions that target these specific network characteristics in order to reduce their vulnerability to relapse.

  20. Substance misuse in Aboriginal Australians.

    Science.gov (United States)

    Gracey, M

    1998-01-01

    Australia's Aborigines lived in isolation from the rest of humanity as successful hunter-gatherers for tens of thousands of years. That isolation ended abruptly with British colonization in the late 18th century and was followed by a traumatic 200 years for Aborigines who are now seriously disadvantaged, socio-economically and in terms of their health standards. It has often been assumed that the Aborigines had no access to psychotropic substances before permanent European contact but several pieces of evidence dispute this view. The history of Aboriginal contact with and usage of intoxicating substances, including alcohol, is extremely complex and affected by a maze of restrictive government policies. These interact with a wide range of other Federal and State policies which have changed rapidly since the late 1960s when Aborigines were first granted the franchise; access to unrestricted drinking followed soon afterwards. Today Aborigines suffer disproportionately to other Australians from the physical and social consequences of excess alcohol consumption, tobacco usage, petrol and other solvent sniffing, usage of marijuana, amphetamines, cocaine and heroin, as well as other drugs. The Aboriginal population is dispersed in cities, towns, fringe settlements, rural and remote areas over this vast continent and there are different patterns of drug usage from place to place. This review attempts to synthesize some of this information in order to give an overview to the history, background, current status of substance misuse by Aborigines as well as some strategies being used to try to overcome this serious problem.

  1. Dermal uptake of petroleum substances.

    Science.gov (United States)

    Jakasa, Ivone; Kezic, Sanja; Boogaard, Peter J

    2015-06-01

    Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount importance. The extent and significance of dermal absorption of eight petroleum substances, representing different classes of hydrocarbons, was evaluated. Literature data on the steady-state flux and permeability coefficient of these substances were evaluated and compared to those predicted by mathematical models. Reported results spanned over 5-6 orders of magnitude and were largely dependent on experimental conditions in particular on the type of the vehicle used. In general, aromatic hydrocarbons showed higher dermal absorption than more lipophilic aliphatics with similar molecular weight. The results showed high variation and were largely influenced by experimental conditions emphasizing the need of performing the experiments under "in use" scenario. The predictive models overestimated experimental absorption. The overall conclusion is that, based on the observed percutaneous penetration data, dermal exposure to petroleum hydrocarbons, even of aromatics with highest dermal absorption is limited and highly unlikely to be associated with health risks under real use scenarios. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Substance misuse and substance use disorders in sex offenders: a review

    NARCIS (Netherlands)

    Kraanen, F.L.; Emmelkamp, P.M.G.

    2011-01-01

    Substance abuse has often been associated with committing sex offenses. In this article, the following will be reviewed: 1) studies that assessed substance abuse in sex offenders; 2) differences in substance abuse among different types of sex offenders; 3) differences in substance abuse between sex

  3. 21 CFR 172.510 - Natural flavoring substances and natural substances used in conjunction with flavors.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Natural flavoring substances and natural substances used in conjunction with flavors. 172.510 Section 172.510 Food and Drugs FOOD AND DRUG ADMINISTRATION....510 Natural flavoring substances and natural substances used in conjunction with flavors. Natural...

  4. Multichip module technology for automotive application

    Science.gov (United States)

    Johnson, R. Wayne; Evans, John L.; Bosley, Larry

    1995-01-01

    Advancements in multichip module technology are creating design freedoms previously unavailable to design engineers. These advancements are opening new markets for laminate based multichip module products. In particular, material improvements in laminate printed wiring boards are allowing multichip module technology to meet more stringent environmental conditions. In addition, improvements in encapsulants and adhesives are enhancing the capabilities of multichip module technology to meet harsh environment. Furthermore, improvements in manufacturing techniques are providing the reliability improvements necessary for use in high quality electronic systems. These advances are making multichip module technology viable for high volume, harsh environment applications like under-the-hood automotive electronics. This paper will provide a brief review of multichip module technology, a discussion of specific research activities with Chrysler for use of multichip modules in automotive engine controllers and finally a discussion of prototype multichip modules fabricated and tested.

  5. Effects of humic substances on the migration of radionuclides: Complexation of actinides with humic substances. 3. Progress report

    International Nuclear Information System (INIS)

    Kim, J.I.; Rhee, D.S.; Buckau, G.; Moulin, V.; Tits, J.; Decambox, P.; Franz, C.; Herrmann, G.; Trautmann, N.; Dierckx, A.; Vancluysen, J.; Maes, A.

    1993-03-01

    The aim of the present research programme is to study the complexation behaviour of actinide ions with humic substances in natural aquifer systems and hence to quantify the effect of humic substances on the actinide migration. Aquatic humic substances commonly found in all groundwaters in different concentrations have a strong tendency towards complexation with actinide ions. This is one of the major geochemical reactions but hitherto least quantified. Therefore, the effect of humic substances on the actinide migration is poorly understood. In the present research programme the complexation of actinide ions with humic substances will be described thermodynamically. This description will be based on a model being as simple as possible to allow an easy introduction of the resulting reaction constants into geochemical modelling of the actinide migration. This programme is a continuation of the activities of the COCO group in the second phase of the CEC-MIRAGE project. The programme consists of the following three main tasks: Task 1: Complexation reactions of actinide ions with well characterized reference and site-specific humic and fulvic acids; Task 2: Competition reactions with major cations in natural groundwaters; Task 3: Validation of the complexation data in natural aquatic systems by comparison of calculation with spectroscopic experiment. (orig./EF)

  6. Toxic or dangerous substances present construction materials

    International Nuclear Information System (INIS)

    Campos Alvarado, A.

    2003-01-01

    The purpose of this investigation is the elaboration of a guide which could be used as a support and consultation concerning the topic of safety in the construction, specifically in the area of the use and managing of material and dangerous substances; considering the possible dangers to medium and long term that some of the common construction materials represent for the health. The gathered information is the result of the review of bibliographical material, the visits to public institutions at national level and to international offices which representation in our country, this way as a work of field and of study of the national market, among others. Besides important consult through the Internet checking many sites of interest with the finality of getting more updated information as possible, like that as the consultation to professionals and workers related to the construction area. (Author) [es

  7. Auditory sensitivity to spectral modulation phase reversal as a function of modulation depth.

    Science.gov (United States)

    Buss, Emily; Grose, John

    2018-01-01

    The present study evaluated auditory sensitivity to spectral modulation by determining the modulation depth required to detect modulation phase reversal. This approach may be preferable to spectral modulation detection with a spectrally flat standard, since listeners appear unable to perform the task based on the detection of temporal modulation. While phase reversal thresholds are often evaluated by holding modulation depth constant and adjusting modulation rate, holding rate constant and adjusting modulation depth supports rate-specific assessment of modulation processing. Stimuli were pink noise samples, filtered into seven octave-wide bands (0.125-8 kHz) and spectrally modulated in dB. Experiment 1 measured performance as a function of modulation depth to determine appropriate units for adaptive threshold estimation. Experiment 2 compared thresholds in dB for modulation detection with a flat standard and modulation phase reversal; results supported the idea that temporal cues were available at high rates for the former but not the latter. Experiment 3 evaluated spectral modulation phase reversal thresholds for modulation that was restricted to either one or two neighboring bands. Flanking bands of unmodulated noise had a larger detrimental effect on one-band than two-band targets. Thresholds for high-rate modulation improved with increasing carrier frequency up to 2 kHz, whereas low-rate modulation appeared more consistent across frequency, particularly in the two-band condition. Experiment 4 measured spectral weights for spectral modulation phase reversal detection and found higher weights for bands in the spectral center of the stimulus than for the lowest (0.125 kHz) or highest (8 kHz) band. Experiment 5 compared performance for highly practiced and relatively naïve listeners, and found weak evidence of a larger practice effect at high than low spectral modulation rates. These results provide preliminary data for a task that may provide a better estimate of

  8. Autoradiographic localization of substance P receptors using 125I substance P

    International Nuclear Information System (INIS)

    Shults, C.W.; Quirion, R.; Jensen, R.T.; Moody, T.W.; O'Donohue, T.L.; Chase, T.N.

    1982-01-01

    This paper describes a method for localization of substance P receptors in the rat central nervous system using 125 I labeled substance P in an autoradiographic procedure. Particularly high densities of substance P receptors were observed in the olfactory bulb, dentate gyrus, amygdala, superior colliculus, and locus coeruleus. Surprisingly low densities of substance P receptors were found in the substantia nigra pars reticulata, a region which contains high concentrations of substance P

  9. Substance Use Among Students of Guilan University of Medical Sciences in Iran in 2005-2006

    Directory of Open Access Journals (Sweden)

    Moosa Kafi

    2009-12-01

    Full Text Available Population pattern in Guilan province represents a dramatic increase in youth population. Regarding high prevalence of substance use among them, its destructive effects and consequences and paucity of previous related studies, this research was performed to determine the prevalence of substance use among students of Guilan University of Medical Sciences (GUMS. We conducted a cross-sectional study in a representative sample of 845 students in 2005-2006. Data were collected by a questionnaire including demographic data and history of substance use and were analyzed by EPI 2002 software and chi-square. 30.1% of students had a history of substance use at least once during their lives. Cigarette (26.36%, alcohol (17.04% and opium (3.86% were the most prevalent used substances. Substance use was significantly associated with male gender, higher age groups, living with friends or alone and being married. There were significant relationships between substance use during past 30 days and studying medicine or dentistry and substance use during life and past 30 days was significantly higher in residency period. This study demonstrated substance use between our samples was considerable and specific interventions to reduce it seem necessary.

  10. Adolescents' media-related cognitions and substance use in the context of parental and peer influences.

    Science.gov (United States)

    Scull, Tracy M; Kupersmidt, Janis B; Parker, Alison E; Elmore, Kristen C; Benson, Jessica W

    2010-09-01

    Two cross-sectional studies investigated media influences on adolescents' substance use and intentions to use substances in the context of exposure to parental and peer risk and protective factors. A total of 729 middle school students (n = 351, 59% female in Study 1; n = 378, 43% female in Study 2) completed self-report questionnaires. The sample in Study 1 was primarily African-American (52%) and the sample in Study 2 was primarily Caucasian (63%). Across the two studies, blocks of media-related cognitions made unique contributions to the prediction of adolescents' current substance use and intentions to use substances in the future above and beyond self-reported peer and parental influences. Specifically, identification with and perceived similarity to media messages were positively associated with adolescents' current substance use and intentions to use substances in the future, and critical thinking about media messages and media message deconstruction skills were negatively associated with adolescents' intention to use substances in the future. Further, peer influence variables (e.g., peer pressure, social norms, peer substance use) acted as risk factors, and for the most part, parental influence variables (e.g., parental pressure to not use, perceived parental reaction) acted as protective factors. These findings highlight the importance of developing an increased understanding of the role of media messages and media literacy education in the prevention of substance use behaviors in adolescence.

  11. Partition of pollution between dissolved and particulate phases: what about emerging substances in urban stormwater catchments?

    Science.gov (United States)

    Zgheib, Sally; Moilleron, Régis; Saad, Mohamed; Chebbo, Ghassan

    2011-01-01

    This paper presents results about the occurrence, the concentrations of urban priority substances on both the dissolved and the particulate phases in stormwater. Samples were collected at the outlet of a dense urban catchment in Paris suburb (2.30 km(2)). 13 chemical groups were investigated including 88 individual substances. Results showed that stormwater discharges contained 45 substances among them some metals, organotins, PAHs, PCBs, alkylphenols, pesticides, phthalates, cholorophenols and one volatile organic compound, i.e. methylene chloride. With respect to the European Water Framework Directive, these substances included 47% of the priority hazardous substances (n = 8), 38% of the priority substances (n = 10). The remaining substances (n = 27) belong to a list of others specific urban substances not included in the Water Framework Directive but monitored during this work. Finally, stormwater quality was evaluated by comparing the substance concentrations to environmental quality standards (EQS) and the particulate content to Canadian sediment quality guidelines. This showed that stormwater was highly contaminated and should be treated before being discharged to receiving waters in order to avoid any adverse impact on the river quality. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Predictors of substance use among young adults transitioning away from high school: a narrative review.

    Science.gov (United States)

    Kirst, Maritt; Mecredy, Graham; Borland, Tracey; Chaiton, Michael

    2014-11-01

    Young adulthood has been shown to be a time of increased substance use. Yet, not enough is known about which factors contribute to initiation and progression of substance use among young adults specifically during the transition year away from high school. A narrative review was undertaken to increase understanding of the predictors of changes in use of tobacco, alcohol, cannabis, other illicit drugs, and mental health problems among young adults during the transition period after high school. A review of academic literature examining predictors of the use of tobacco, alcohol and cannabis, and co-morbidities (e.g., co-occurring substance use and/or mental health issues) among young adults transitioning from high school to post-secondary education or the workforce. Twenty six studies were included in the review. The majority of the studies (19) examined substance use during the transition from high school to post-secondary settings. Seven studies examined substance use in post-secondary settings. The studies consistently found that substance use increases among young adults as they transition away from high school. During the transition away from high school, common predictors of substance use include substance use in high school, and peer influence. Common predictors of substance use in post-secondary education include previous substance use, peer influence, psychological factors and mental health issues. Conclusions/Importance: Further research on social contextual influences on substance use, mental health issues, gender differences and availability of substances during the transition period is needed to inform the development of new preventive interventions for this age group.

  13. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  14. Functional role for suppression of the insular-striatal circuit in modulating interoceptive effects of alcohol.

    Science.gov (United States)

    Jaramillo, Anel A; Agan, Verda E; Makhijani, Viren H; Pedroza, Stephen; McElligott, Zoe A; Besheer, Joyce

    2017-09-27

    The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4D i designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular-striatal circuit in modulating behavior under a drug stimulus control. © 2017 Society for the Study of Addiction.

  15. Maternal substance use and integrated treatment programs for women with substance abuse issues and their children: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Milligan Karen

    2010-09-01

    Full Text Available Abstract Background The rate of women with substance abuse issues is increasing. Women present with a unique constellation of risk factors and presenting needs, which may include specific needs in their role as mothers. Numerous integrated programs (those with substance use treatment and pregnancy, parenting, or child services have been developed to specifically meet the needs of pregnant and parenting women with substance abuse issues. This synthesis and meta-analysis reviews research in this important and growing area of treatment. Methods We searched PsycINFO, MedLine, PubMed, Web of Science, EMBASE, Proquest Dissertations, Sociological Abstracts, and CINAHL and compiled a database of 21 studies (2 randomized trials, 9 quasi-experimental studies, 10 cohort studies of integrated programs published between 1990 and 2007 with outcome data on maternal substance use. Data were summarized and where possible, meta-analyses were performed, using standardized mean differences (d effect size estimates. Results In the two studies comparing integrated programs to no treatment, effect sizes for urine toxicology and percent using substances significantly favored integrated programs and ranged from 0.18 to 1.41. Studies examining changes in maternal substance use from beginning to end of treatment were statistically significant and medium sized. More specifically, in the five studies measuring severity of drug and alcohol use, the average effect sizes were 0.64 and 0.40, respectively. In the four cohort studies of days of use, the average effect size was 0.52. Of studies comparing integrated to non-integrated programs, four studies assessed urine toxicology and two assessed self-reported abstinence. Overall effect sizes for each measure were not statistically significant (d = -0.09 and 0.22, respectively. Conclusions Findings suggest that integrated programs are effective in reducing maternal substance use. However, integrated programs were not

  16. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

    2008-01-01

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  17. Deep brain stimulation in addiction due to psychoactive substance use.

    Science.gov (United States)

    Kuhn, Jens; Bührle, Christian P; Lenartz, Doris; Sturm, Volker

    2013-01-01

    Addiction is one of the most challenging health problems. It is associated with enormous individual distress and tremendous socioeconomic consequences. Unfortunately, its underlying mechanisms are not fully understood, and pharmacological, psychological, or social interventions often fail to achieve long-lasting remission. Next to genetic, social, and contextual factors, a substance-induced dysfunction of the brain's reward system is considered a decisive factor for the establishment and maintenance of addiction. Due to its successful application and approval for several neurological disorders, deep brain stimulation (DBS) is known as a powerful tool for modulating dysregulated networks and has also been considered for substance addiction. Initial promising case reports of DBS in alcohol and heroin addiction in humans have recently been published. Likewise, results from animal studies mimicking different kinds of substance addiction point in a similar direction. The objective of this review is to provide an overview of the published results on DBS in addiction, and to discuss whether these preliminary results justify further research, given the novelty of this treatment approach. © 2013 Elsevier B.V. All rights reserved.

  18. The Anatomy of a Successful Caribbean Substance Abuse Training Programme

    Directory of Open Access Journals (Sweden)

    SD Reid

    2015-03-01

    Full Text Available Objectives: This paper describes the components of the Caribbean Institute on Alcoholism and Other Drug Problems (CARIAD, a long-standing substance abuse training programme. It seeks to explain how certain strategies and pedagogic techniques may be contributing to its success. Methods: Authors deconstruct the core elements of CARIAD to demonstrate how the programme effectively meets the characteristics of a community of practice. The processes used to develop the learning community and the specific pedagogic strategies and techniques that foster collaborative knowledge construction and sharing are described. Results: Caribbean Institute on Alcoholism and Other Drug Problems brings together a multi-disciplinary, multi-national group of individuals with interest in substance abuse. The programme provides a range of formal and informal learning activities which focus on sharing best practices and creating new sociocultural relevant knowledge to advance the domain of professional practice in substance abuse. The components of CARIAD promote interactivity, rapid bonding and a sense of identity. Caribbean Institute on Alcoholism and Other Drug Problems provides a unique platform for cultural sharing that gives participants an opportunity to reveal insights into local and regional expressions of substance abuse challenges. Participants, however, recognize the absence of structured continuity and the diminution of what could be accomplished by graduates over time. Conclusion: The success of CARIAD as a regional learning platform may be related to its success as a Caribbean community of practice for substance abuse. Caribbean Institute on Alcoholism and Other Drug Problems would do well to sustain the community of practice, generating and maintaining ongoing participation and collaboration among graduates. This can potentially serve to create new strategies for advancing the region in the area of substance abuse.

  19. [Reconsideration of nicotine and other substance dependence: a clue from dependence-related mentation including reward, motivation, learning, delusion and hallucination toward understanding the concept of non-substance-related addiction].

    Science.gov (United States)

    Miyata, Hisatsugu

    2013-11-01

    Nicotine produces core symptoms of substance dependence (craving and withdrawal) without any psychotic symptoms. The psychopharmacological structure of craving is hypothesized to be constituted by three components: the primary reinforcing property of a substance, the secondary reinforcing property of that substance (conditioned aspects of the environment, such as contextual or specific cues associated with substance taking), and the negative affective motivational property during withdrawal (i.e. the desire to avoid the dysphoric withdrawal symptoms elicits craving). Among the three components, the primary reinforcing property of a substance forms the most fundamental factor for establishing substance dependence. Sensitization or reverse tolerance observed in locomotor activity of animals, which had been believed to be a methamphetamine psychosis model, is demonstrated to reflect the establishment of conditioned reinforcement. Finally, non-substance-related addiction such as gambling, internet, and sex is discussed. From the aspect of the above hypothetical psychopharmacological structure of craving, the most significant difference between substance dependence and non-substance-related addiction is that the primary reinforcing property of non-substance reward is relatively intangible in comparison with that of a substance of abuse.

  20. Airborne psychotropic substances in eight Italian big cities: Burdens and behaviours

    International Nuclear Information System (INIS)

    Cecinato, Angelo; Balducci, Catia; Romagnoli, Paola; Perilli, Mattia

    2012-01-01

    Psychotropic substances were monitored in eight big cities of Italy over one year, starting in May 2010, in the frame of the Ariadrugs Project. Yearly average concentrations ranged from 0.02 ± 0.01 to 0.26 ± 0.11 ng/m 3 for cocaine, from 0.05 ± 0.05 to 0.96 ± 1.37 ng/m 3 for cannabinoids, from 16 ± 6 to 61 ± 28 ng/m 3 for nicotine, and from 1.0 ± 0.8 to 8 ± 7 ng/m 3 for caffeine. Palermo and Turin were the cities suffering the lowest and the highest psychotropic substance concentrations, respectively. Nicotine and cocaine exhibited trends less seasonally modulated than common air toxicants. Caffeine and cannabinoids peaked in winter dropping close to zero from May to August. In Rome, where various anthropic contours were investigated in February 2011, differences were observed both in net concentrations and ratios of psychotropic substances vs. regulated toxicants. Ambient drugs look as a consequence of addiction and their burdens give insights about the corresponding consumes. - Highlights: ► Psychotropic substances (PSs) were monitored in eight big Italian cities over one year. ► The site-to-site and year time modulations of PSs were investigated. ► The PSs contents in the air were plotted vs. air toxicants (O 3 , NO 2 , PM 10 , PAHs). ► The relationships among drug modulations and meteo-climatic variables were studied. ► The results were compared to those of previous investigations. - Both licit and illicit psychotropic substances modulate in space and time along Italy, resulting influenced by both the environmental and human contours.

  1. Adolescent substance use behavior and suicidal behavior for boys and girls: a cross-sectional study by latent analysis approach

    OpenAIRE

    Wang, Peng-Wei; Yen, Cheng-Fang

    2017-01-01

    Background Adolescent suicidal behavior may consist of different symptoms, including suicidal ideation, suicidal planning and suicidal attempts. Adolescent substance use behavior may contribute to adolescent suicidal behavior. However, research on the relationships between specific substance use and individual suicidal behavior is insufficient, as adolescents may not use only one substance or develop only one facet of suicidal behavior. Latent variables permit us to describe the relationships...

  2. Fast Convolution Module (Fast Convolution Module)

    National Research Council Canada - National Science Library

    Bierens, L

    1997-01-01

    This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

  3. Specification and development of the sharing memory data management module for a nuclear processes simulator; Especificacion y desarrollo del modulo de administracion de datos de memoria compartida para un simulador de procesos nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Telesforo R, D. [UNAM, DEPFI, Campus Morelos, Jiutepec, Morelos (Mexico)]. e-mail: cchavez2@cableonline.com.mx

    2003-07-01

    Actually it is developed in the Engineering Faculty of UNAM a simulator of nuclear processes with research and teaching purposes. It consists of diverse modules, included the one that is described in the present work that is the shared memory module. It uses the IPC mechanisms of the UNIX System V operative system, and it was codified with C language. To model the diverse components of the simulator the RELAP code is used. The function of the module is to generate locations of shared memory for to deposit in these the necessary variables for the interaction among the diverse ones processes of the simulator. In its it will be able read and to write the information that generate the running of the simulation program, besides being able to interact with the internal variables of the code in execution time. The graphic unfolding (mimic, pictorials, tendency graphics, virtual instrumentation, etc.) they also obtain information of the shared memory. In turn, actions of the user in interactive unfolding, they modify the segments of shared memory, and the information is sent to the RELAP code to modify the simulation course. The program has two beginning modes: automatic and manual. In automatic mode taking an enter file of RELAP (indta) and it joins in shared memory, the control variables that in this appear. In manual mode the user joins, he reads and he writes the wanted control variables, whenever they exist in the enter file (indta). This is a dynamic mode of interacting with the simulator in a direct way and of even altering the values as when its don't exist in the board elements associated to the variables. (Author)

  4. National substance use patterns on Twitter.

    Directory of Open Access Journals (Sweden)

    Hsien-Wen Meng

    Full Text Available We examined openly shared substance-related tweets to estimate prevalent sentiment around substance use and identify popular substance use activities. Additionally, we investigated associations between substance-related tweets and business characteristics and demographics at the zip code level.A total of 79,848,992 tweets were collected from 48 states in the continental United States from April 2015-March 2016 through the Twitter API, of which 688,757 were identified as being related to substance use. We implemented a machine learning algorithm (maximum entropy text classifier to estimate sentiment score for each tweet. Zip code level summaries of substance use tweets were created and merged with the 2013 Zip Code Business Patterns and 2010 US Census Data.Quality control analyses with a random subset of tweets yielded excellent agreement rates between computer generated and manually generated labels: 97%, 88%, 86%, 75% for underage engagement in substance use, alcohol, drug, and smoking tweets, respectively. Overall, 34.1% of all substance-related tweets were classified as happy. Alcohol was the most frequently tweeted substance, followed by marijuana. Regression results suggested more convenience stores in a zip code were associated with higher percentages of tweets about alcohol. Larger zip code population size and higher percentages of African Americans and Hispanics were associated with fewer tweets about substance use and underage engagement. Zip code economic disadvantage was associated with fewer alcohol tweets but more drug tweets.The patterns in substance use mentions on Twitter differ by zip code economic and demographic characteristics. Online discussions have great potential to glorify and normalize risky behaviors. Health promotion and underage substance prevention efforts may include interactive social media campaigns to counter the social modeling of risky behaviors.

  5. Computing optimal interfacial structure of modulated phases

    OpenAIRE

    Xu, Jie; Wang, Chu; Shi, An-Chang; Zhang, Pingwen

    2016-01-01

    We propose a general framework of computing interfacial structures between two modulated phases. Specifically we propose to use a computational box consisting of two half spaces, each occupied by a modulated phase with given position and orientation. The boundary conditions and basis functions are chosen to be commensurate with the bulk structures. It is observed that the ordered nature of modulated structures stabilizes the interface, which enables us to obtain optimal interfacial structures...

  6. The moderating effects of peer substance use on the family structure-adolescent substance use association: quantity versus quality of parenting.

    Science.gov (United States)

    Eitle, David

    2005-06-01

    This study examines the association between family structure and adolescent substance use, specifically focusing on the potential conditioning effects of the level of exposure to substance-using peers. Using data from a statewide study of Florida students, tobacco, alcohol, marijuana, and other illicit drug use was regressed on measures of family structure, exposure to deviant peers, family process variables (including supervision, attachment, and discipline), and an array of salient predictors of adolescent substance use. Logistic regression analyses revealed that the level of exposure to substance-using peers moderates the relationship between family structure and substance use for three of the four dependent variables. The core finding is that living with two natural parents serves as a protective factor against using tobacco, alcohol, or other illicit drugs, but only under conditions when exposure to deviant peers is lowest. Under conditions when exposure to deviant peers is highest, teens residing in a traditional two-parent family are most likely to report substance use. However, some evidence suggests that this latter finding may be due to differences in the duration of exposure to deviant peers. These findings reinforce the need to continue to explore how the quantity of parenting may provide additional protection against adolescent substance use beyond quality of parenting factors.

  7. Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement.

    Science.gov (United States)

    Carey, Caitlin E; Agrawal, Arpana; Bucholz, Kathleen K; Hartz, Sarah M; Lynskey, Michael T; Nelson, Elliot C; Bierut, Laura J; Bogdan, Ryan

    2016-01-01

    Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium's Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)-and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.

  8. Family Structure and Adolescent Substance Use: An International Perspective.

    Science.gov (United States)

    Hoffmann, John P

    2017-11-10

    Numerous studies indicate that family structure is a key correlate of adolescent substance use. Yet there are some important limitations to this research. Studies have been conducted mainly in the United States, with relatively few studies that have compared family structure and youth substance use across nations. There is also a lack of recognition of the complexity of family types prevalent in contemporary global society. Moreover, there remains a need to consider personal, interpersonal, and macro-level characteristics that may help account for the association between family structure and youth substance use. This study uses data from 37 countries to examine several models that purport to explain the association between family structure and substance use. The data are from the 2005-2006 WHO-sponsored Health Behaviour in School-Aged Children (HBSC) (n = 193,202). Multilevel models, including linear, probit, and structural equation models (SEMs), were used to test several hypotheses. The results suggest that time spent with friends largely accounted for the association between specific types of family structures and frequency of alcohol use and getting drunk, but that cannabis use was negatively associated with living with both biological parents irrespective of other factors.

  9. Maternal neural responses to infant cries and faces: relationships with substance use

    Directory of Open Access Journals (Sweden)

    Nicole eLandi

    2011-06-01

    Full Text Available Substance abuse in pregnant and recently postpartum women is a major public health concern because of effects on the infant and on the ability of the adult to care for the infant. In addition to the negative health effects of teratogenic substances on fetal development, substance use can contribute to difficulties associated with the social and behavioral aspects of parenting. Neural circuits associated with parenting behavior overlap with circuits involved in addiction (e.g., frontal, striatal and limbic systems and thus may be co-opted for the craving/reward cycle associated with substance use and abuse and be less available for parenting. The current study investigates the degree to which neural circuits associated with parenting are disrupted in mothers who are substance-using. Specifically, we used functional magnetic resonance imaging to examine the neural response to emotional infant cues (faces and cries in substance-using compared to non-using mothers. In response to both faces (of varying emotional valence and cries (of varying distress levels, substance-using mothers evidenced reduced neural activation in regions that have been previously implicated in reward and motivation as well as regions involved in cognitive control. Specifically, in response to faces, substance users showed reduced activation in prefrontal regions, including the dorsolateral and ventromedial prefrontal cortex, as well as visual processing (occipital lobes and limbic regions (parahippocampus and amygdala. Similarly, in response to infant cries substance-using mothers showed reduced activation relative to non-using mothers in prefrontal regions, auditory sensory processing regions, insula and limbic regions (parahippocampus and amygdala. These findings suggest that infant stimuli may be less salient for substance-using mothers, and such reduced saliency may impair developing infant-caregiver attachment and the ability of mothers to respond appropriately to their

  10. Substance Use among Adolescent Mothers: A Review.

    Science.gov (United States)

    Chapman, Shawna L Carroll; Wu, Li-Tzy

    2013-05-01

    Maternal substance abuse is a critical problem, and adolescent mothers appear to be at high risk for such behaviors. We review studies on postpartum adolescent substance use to explore the extent of this problem and avenues for new research. Authors screened 1,300 studies, identifying 12 articles on substance use among postpartum adolescent mothers for this review. Adolescent mothers reported greater substance use before pregnancy compared to other adolescent females. Although some adolescents continued substance use during pregnancy, most stopped using only to resume within six months after birth. Comparisons of use to national samples of nulliparous adolescent females showed a higher prevalence of substance use in this population. Substances used often varied by race/ethnicity, with white mothers more likely to smoke cigarettes and use marijuana, and Black mothers more likely than whites to drink and use drugs. Of all identified studies, only one focused on Hispanics. Beliefs about drug use grew less negative as girls transitioned from pregnancy to parenthood. As they transitioned to adulthood, substance use remained prevalent and stable. Psychological distress and low self-esteem appeared to influence continued use. Friends' cigarette smoking predicted early initiation of and persistent smoking, while increased education predicted quitting. Early initiation of substances often predicted problem behaviors. Adolescent mothers are a vulnerable population, implicating use of problem behavior theory or the self-medication hypothesis in future research. Multiple avenues for new studies are needed to help identify effective treatment and intervention for this understudied population.

  11. Humic Substances in waters for supply

    International Nuclear Information System (INIS)

    Camargo Valero, Miller; Cruz Torres, Luis Eduardo

    1999-01-01

    The humic substances make part of the degradation products of the organic matter of the soil and they are incorporate to the superficial waters for the action of laundry that they carry out by the superficial waters. These substances have been recognized as precursors in the formation of the disinfections sub-products, with free chlorine in treatment of drinkable water plants. The disinfections sub-product and the compound organic halogens, they have been classified potentially in human as cancerigenic substances, and therefore the interest in knowing more about the precursors substances, mechanisms of formation of disinfections sub-products, national situation and methods to diminish their formation

  12. Refractory organic substances in the environment

    National Research Council Canada - National Science Library

    Frimmel, F. H

    2002-01-01

    ... and its Quality Control in Fractions of Refractory Organic Substances and the Corresponding Original Water Samples 39 Introduction 39 Description of Analytical Methods 41 Sample Treatment 41 Fl...

  13. Module theory, extending modules and generalizations

    CERN Document Server

    Tercan, Adnan

    2016-01-01

    The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

  14. List of hazardous substances for 1995. Hazardous substances at the working place; Gefahrstoffliste 1995. Gefahrstoffe am Arbeitsplatz

    Energy Technology Data Exchange (ETDEWEB)

    Pflaumbaum, W. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany); Blome, H. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany); Kleine, H. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany); Stamm, R. [Berufsgenossenschaftliches Inst. fuer Arbeitssicherheit, St. Augustin (Germany)

    1995-04-01

    The List of Hazardous Substances for 1995 contains a summarizing table of the most important regulations concerning safety and health at the working place together with supplementary information. The present version, compiled by the Berufsgenossenschaftliche Institut fuer Arbeitssicherheit (Trade Associations` Institute for Working Safety), is an update of the List of Hazardous Substances for 1994. The List contains the prescribed classifications and designations of substances and preparations pursuant to the EC Directive 67/548/EEC (including the 20th amendment); the substances contained in the ``List of carcinogenic, mutagenic and reproduction-endangering substances`` (TRGS 905); the air pollution limit values of MAK and TRK (``Air pollution limit values at the working place``, TRGS 900); and the Biological Tolerance Values (BAT, TRGS 903). At the end it provides information, amongst other things, on measuring methods (DFG, ZH1/120, BIA desk folder, HSE, NIOSH, OSHA), industrial medicine, substance-specific regulations of the Ordinance On Hazardous Substances (GefStoffV), Ordinance of Prohibitions Concerning Chemicals (ChemVerbotsV), and Hazardous Substances Technical Code (TRGS), and on regulations of the trade associations. The amendments to the Technical Code (e.g. TRGS 900 and 905) published in early 1995 have also been incorporated. (orig./SR) [Deutsch] Das Berufsgenossenschaftliche Institut fuer Arbeitssicherheit - BIA hat in der Gefahrstoffliste 1995 die wichtigsten Regelungen fuer die Sicherheit und Gesundheit am Arbeitsplatz sowie ergaenzende Hinweise in einer Tabelle zusammengefasst. Die vorliegende Version aktualisiert die Gefahrstoffliste aus dem Jahr 1994. Die Liste enthaelt die vorgeschriebenen Einstufungen und Kennzeichnungen von Stoffen und Zubereitungen gemaess der EU-Richtlinie 67/548/EWG (einschliesslich 20. Anpassung) sowie die in der TRGS 905 ``Verzeichnis krebserzeugender, erbgutveraendernder und fortpflanzungsgefaehrdender Stoffe

  15. Sequential assessment via daphnia and zebrafish for systematic toxicity screening of heterogeneous substances.

    Science.gov (United States)

    Jang, Gun Hyuk; Park, Chang-Beom; Kang, Benedict J; Kim, Young Jun; Lee, Kwan Hyi

    2016-09-01

    Environment and organisms are persistently exposed by a mixture of various substances. However, the current evaluation method is mostly based on an individual substance's toxicity. A systematic toxicity evaluation of heterogeneous substances needs to be established. To demonstrate toxicity assessment of mixture, we chose a group of three typical ingredients in cosmetic sunscreen products that frequently enters ecosystems: benzophenone-3 (BP-3), ethylhexyl methoxycinnamate (EHMC), and titanium dioxide nanoparticle (TiO2 NP). We first determined a range of nominal toxic concentration of each ingredient or substance using Daphnia magna, and then for the subsequent organismal level phenotypic assessment, chose the wild-type zebrafish embryos. Any phenotype change, such as body deformation, led to further examinations on the specific organs of transgenic zebrafish embryos. Based on the systematic toxicity assessments of the heterogeneous substances, we offer a sequential environmental toxicity assessment protocol that starts off by utilizing Daphnia magna to determine a nominal concentration range of each substance and finishes by utilizing the zebrafish embryos to detect defects on the embryos caused by the heterogeneous substances. The protocol showed additive toxic effects of the mixtures. We propose a sequential environmental toxicity assessment protocol for the systematic toxicity screening of heterogeneous substances from Daphnia magna to zebrafish embryo in-vivo models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography

    International Nuclear Information System (INIS)

    Gates, T.S.; Zimmerman, R.P.; Mantyh, C.R.; Vigna, S.R.; Maggio, J.E.; Welton, M.L.; Passaro, E.P. Jr.; Mantyh, P.W.

    1988-01-01

    Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125 I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: (1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; (2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; (3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and (4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells

  17. Decisions to regulate genotoxic substances

    Energy Technology Data Exchange (ETDEWEB)

    Bengtsson, G

    1988-07-01

    Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

  18. Decisions to regulate genotoxic substances

    International Nuclear Information System (INIS)

    Bengtsson, G.

    1988-01-01

    Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

  19. Organic substances of bituminous shales

    Energy Technology Data Exchange (ETDEWEB)

    Lanin, V A; Pronina, M V

    1944-01-01

    Samples of Gdov (Estonia) and Volga (Russia) oil shales were oxidized by alkaline permanganate to study the distribution of carbon and the composition of the resulting oxidation products. Gdov shale was rather stable to oxidation and, after 42 hours 61.2 percent of the organic material remained unoxidized. Five hundred hours were required for complete oxidation, and the oxidation products consisted of CO/sub 2/, acetic, oxalic, and succinic acids. The oxidation products from Volga shale consisted of CO/sub 2/, acetic, oxalic, succinic, adipic, phthalic, benzenetricarboxylic, benzenetetracarboxylic, and benzenepentacarboxylic acids. The results indicated that Gdov shale is free of humic substances and is of sapropelic origin, while Volga shale is of sapropelic-humic origin.

  20. Transportation Brokerage: An Instructional Module.

    Science.gov (United States)

    Hayden, Linda

    A concept-based introduction to transportation brokerage is provided in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business, marketing, and technology. The concept of transportation brokerage is defined as an assignment of the management of a specific element of a…

  1. Substance abuse precedes Internet addiction.

    Science.gov (United States)

    Lee, Young Sik; Han, Doug Hyun; Kim, Sun Mi; Renshaw, Perry F

    2013-04-01

    The purpose of the current study was to evaluate possible overlapping substance abuse and internet addiction in a large, uniformly sampled population, ranging in age from 13 to 18 years. Participants (N=73,238) in the current study were drawn from the 6th Korea Youth Risk Behavior Web-based Survey (KYRBWS-V) for students from 400 middle schools and 400 high schools in 16 cities within South Korea. Of adolescent internet users, 85.2% were general users (GU), 11.9% were users with potential risk for internet addiction (PR), and 3.0% were users with high risk for internet addiction (HR). There was a difference in the number of students with alcohol drinking among the GU, PR, and HR groups (20.8% vs 23.1% vs 27.4%). There was a difference in the number of students who smoked among the GS, PR, and HR groups (11.7% vs 13.5% vs 20.4%). There was a difference in the number of students with drug use among the GU, PR, and HR groups (1.7% vs 2.0% vs 6.5%). After adjusting for sex, age, stress, depressed mood, and suicidal ideation, smoking may predict a high risk for internet addiction (OR=1.203, p=0.004). In addition, drug use may predict a high risk for internet addiction (OR=2.591, paddiction have vulnerability for addictive behaviors, co-morbid substance abuse should be evaluated and, if found, treated in adolescents with internet addiction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Risk factors for substances use and misuse among young people in France: What can we learn from the Substance Use Risk Profile Scale?

    Science.gov (United States)

    Ali, A; Carré, A; Hassler, C; Spilka, S; Vanier, A; Barry, C; Berthoz, S

    2016-06-01

    The prevention of addictions in young people is a challenge for Mental and Public Health policies, and requires specific risk-screening tools. Specific personality traits, as assessed using the Substance Use Risk Profile Scale (SURPS), could play a key role in the onset and escalation of substance use. This study aimed to examine (1) measurement invariance across age and gender (2) the effects of age and gender on associations between SURPS scores and the most frequently-consumed substances. Analyses were based on the responses from 5069 participants (aged 14-20 years) from the 2011 ESPAD-France dataset. Substance-use outcomes were experimentation and current frequency of alcohol, tobacco and cannabis use, and drunkenness. Our approach, consisting in analysing measurement and structural invariance and interaction terms, established the stability of (i) SURPS profiles, and (ii) relationships between these scores and substance experimentation and use over a developmental period ranging from mid-adolescence to early adulthood. Measurement invariance across genders was also confirmed despite the absence of scalar invariance for 2 items. Significant interactions between gender and SURPS factors were established, highlighting differential vulnerability, especially concerning Hopelessness and experimentation of alcohol and drunkenness, or Impulsivity and tobacco experimentation. Finally, Anxiety Sensitivity could be protective against substance use, especially for cannabis in girls. Our results suggest the relevance of the SURPS to assess vulnerability towards drug use, and underline the need to consider gender differences in addiction risks. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Peer Substance Use and Homelessness Predicting Substance Abuse from Adolescence Through Early Adulthood

    OpenAIRE

    Tompsett, Carolyn J.; Domoff, Sarah E.; Toro, Paul A.

    2013-01-01

    Adolescents who experience homelessness are at higher risk for abusing substances, and for being exposed to substance-using peers. The current study used a longitudinal design to track substance abuse, affiliation with substance-using peers, and episodes of homelessness among a sample of 223 adolescents who were homeless at thebaseline data collection and 148 adolescents who were housed at baseline. Participants were interviewed at six waves over 6.5 years, covering an age rang...

  4. Customized PEC modules. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, Martin B. (DTI, Taastrup (Denmark))

    2012-07-01

    The purpose of the project ''Customized PEC modules'' was to move from the production hand-made individual DSCs (dye-sensitized solar cells) in the laboratory to the production of DSC modules in a semi-automated process. At the same time allowing sufficient variation in the product's specification for real tailoring of the product to the application. The tailoring can be related to the module's electrical output and size, but also to the possibility of designing patterns for decoration or communication purposes by playing around with the shape, size and layout of the individual cells forming the module. This was to be accomplished mainly by screen printing of DSC components on glass substrates at Mekoprint. For reaching this goal the work was divided into a number of steps. The central part of the work done was in the initial conception activity and the following manufacturing activity. An activity regarding optimization included several tasks of optimization and adaptation of the existing laboratory process for manufacturing of the DSCs. Finally, work focused on international activities was done. All the steps needed for the production of customized DSC modules have been demonstrated in this project. In combination with the development of a high performing printable sealant and sealing method all the prerequisites for producing customized DSC modules have been demonstrated. (LN)

  5. Determination of specificity influencing residues for key transcription factor families

    DEFF Research Database (Denmark)

    Patel, Ronak Y.; Garde, Christian; Stormo, Gary D.

    2015-01-01

    Transcription factors (TFs) are major modulators of transcription and subsequent cellular processes. The binding of TFs to specific regulatory elements is governed by their specificity. Considering the gap between known TFs sequence and specificity, specificity prediction frameworks are highly de...

  6. Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement

    Directory of Open Access Journals (Sweden)

    Caitlin E Carey

    2016-08-01

    Full Text Available Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS for cross-disorder psychopathology (CROSS were generated based on the Psychiatric Genomics Consortium’s Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB. Follow-up analyses evaluated specific associations between each of the 5 psychiatric disorders which comprised CROSS—attention deficit hyperactivity disorder (ADHD, autism spectrum disorder (AUT, bipolar disorder (BIP, major depressive disorder (MDD, and schizophrenia (SCZ—and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p<0.001. After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: A MDD PRS and non-problem cannabis use, B MDD PRS and severe cocaine dependence, C SCZ PRS and non-problem cannabis use and severe cannabis dependence, and D SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.

  7. Current Trends in Adolescent Substance Use in Jamaica

    Directory of Open Access Journals (Sweden)

    U Atkinson

    2015-03-01

    Full Text Available Objective: National secondary school-based drug surveys facilitate the identification and understanding of patterns of substance use among adolescents, associated risk and protective factors which exist and inform prevention and treatment interventions and policies which are appropriate for resource constrained settings. This paper analyses current trends as well as reviews trends from the last National School Survey conducted by the National Council on Drug Abuse in 2006. Method: The study utilized a survey design that included a representative sample of secondary school students. Data were collected from 3365 students from 38 schools across the island. The study made specific reference to the prevalence of alcohol, tobacco cigarette, marijuana and inhalant use among secondary school students. Results: The most widely used substances among the sample were alcohol, tobacco cigarettes, marijuana and solvents/inhalants. A large number of students (64% reported a lifetime prevalence of alcohol use. Alcohol use was also the highest for one-year (44% and one-month (33.6% use. While lifetime use of tobacco cigarette was higher than marijuana, one-year and one-month use of marijuana was higher than that of tobacco cigarette. There has been a slight increase in the age of initiation for alcohol, tobacco cigarette and marijuana use. There has also been a significant decrease (approximately 50% in lifetime, past year and past month prevalence of inhalant use since the 2006 secondary school survey. Conclusions: Alcohol continues to be the substance most widely used by Jamaican adolescents, followed by tobacco, marijuana and inhalants. Though the average age of first use has slightly increased for all substances, prevalence remains a concern. As such, innovative school-based interventions are required to assist in reducing substance use among Jamaican adolescents.

  8. Interventions for Adolescent Substance Abuse: An Overview of Systematic Reviews.

    Science.gov (United States)

    Das, Jai K; Salam, Rehana A