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Sample records for gamma-hydroxybutyrate ghb precursors

  1. Determination of gamma-hydroxybutyrate (GHB) and its precursors in blood and urine samples: a salting-out approach.

    PubMed

    Kankaanpää, Aino; Liukkonen, Raija; Ariniemi, Kari

    2007-08-06

    Gamma-hydroxybutyrate (GHB) is an increasingly popular drug of abuse that causes stimulation, euphoria, anxiolysis or hypnosis, depending on the dose used. Low doses of the drug are used recreationally, and also implicated in drug-facilitated sexual assaults. Because of the unusually steep dose-response curves, accidental GHB overdosing, leading to coma, seizures or death can occur. Being a controlled substance, GHB is often substituted with its non-scheduled precursors gamma-butyrolactone (GBL) and 1,4-butanediol (BD), which are rapidly metabolized into GHB in the body. Here we describe an assay for GHB, GBL and BD in blood and/or urine samples. GHB and BD were extracted from diluted 200 microL aliquots of samples with t-butylmethylether (plus internal standard benzyl alcohol) in test tubes preloaded with NaCl. After acidification and centrifugation the solvent phase was transferred to a test tube preloaded with Na(2)SO(4), incubated for 30 min, centrifuged again, and evaporated in vacuum. The residue was mixed with N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA) in acetonitrile, and injected into a GC-MS. When analyzing GBL, the salting-out step was omitted, and analysis was performed with a GC-FID apparatus. As revealed by the validation data this procedure is suitable for quantitative determination of GHB and its precursors in blood and/or urine samples.

  2. Preference for Gamma-Hydroxybutyrate (GHB) in Current Users

    ERIC Educational Resources Information Center

    Roll, John M.; Newton, Thomas; Chudzynski, Joy; Cameron, Jennifer M.; McPherson, Sterling; Fong, Tim; Torrington, Matt

    2012-01-01

    Gamma-hydroxybutyrate (GHB) is a drug with significant abuse potential. The present study aimed to assess the relative value of escalating doses of GHB to current GHB users via the Multiple Choice Procedure (MCP), and to validate that the dose rated highest with the MCP would be self-administered at a greater rate than placebo. Participants were 5…

  3. Preference for gamma-hydroxybutyrate (GHB) in current users.

    PubMed

    Roll, John M; Newton, Thomas; Chudzynski, Joy; Cameron, Jennifer M; McPherson, Sterling; Fong, Timothy; Torrington, Matt

    2012-05-01

    Gamma-hydroxybutyrate (GHB) is a drug with significant abuse potential. The present study aimed to assess the relative value of escalating doses of GHB to current GHB users via the Multiple Choice Procedure (MCP), and to validate that the dose rated highest with the MCP would be self-administered at a greater rate than placebo. Participants were 5 current GHB users who were not currently trying to stop using GHB. To examine the value of escalating doses of GHB, the following doses of GHB were used: 0 (placebo), 12.5, 25, 37.5, and 50 mg/kg. Participants typically assigned higher doses of GHB had higher crossover points on the MCP. During choice sessions, participants made repeated choices between administering GHB, placebo or nothing. All participants selected GHB exclusively (5 out of 5 instances) except for one participant who selected GHB on 4 out of 5 instances, thus 96% (i.e., 24/25) of choices were for active GHB. Based on these data, GHB appears likely to function as a dose-dependent reinforcer for humans based on our sample.

  4. The clinical development of gamma-hydroxybutyrate (GHB).

    PubMed

    Wedin, Gregory P; Hornfeldt, Carl S; Ylitalo, Lisa M

    2006-01-01

    The discovery of gamma-hydroxybutyrate (GHB) over 40 years ago led to its immediate use as a general anesthetic agent. Subsequent research demonstrated that GHB is an endogenous compound in the mammalian brain and current research suggests that GHB is a probable neurotransmitter. In the United States, reports of anabolic effects lead to its misuse among body builders during the 1980's while the intoxicating properties of the drug lead to its popularization as a substance of abuse during the 1990's. GHB became associated with reports of drug-facilitated sexual assault and cases of physical dependence and withdrawal. Efforts to ban GHB caused increased use of GHB analogues and pro-drugs. Against this backdrop, GHB was being developed for the treatment of narcolepsy, leading to the approval of Xyrem (sodium oxybate) oral solution in 2002 for the treatment of cataplexy in patients with narcolepsy. A risk management program permits the safe handling and distribution of the approved product, minimizes the risk for diversion, provides professional and patient education about the risks and benefits of sodium oxybate, and includes physician and patient registries. Post-marketing surveillance indicates sodium oxybate has an acceptable safety profile and presents minimal risk for the development of physical dependence.

  5. EXPERIENCES OF GAMMA HYDROXYBUTYRATE (GHB) INGESTION: A FOCUS GROUP STUDY

    PubMed Central

    Barker, Judith C.; Harris, Shana L.; Dyer, Jo E.

    2008-01-01

    GHB (gamma hydroxybutyrate) is a significant new drug of abuse added to the United States Controlled Substance Act in 2000. The majority of the published literature on GHB consists of clinical case reports, mainly from emergency departments, and a collection of laboratory-based studies, focused mainly on anesthesia. While comments about the various experiences and behaviors of human users are often included in such studies or reports, these aspects of GHB are only just beginning to be systematically investigated or detailed. Reported here are data from a qualitative study using focus group methods on the consumption habits, experiences, and beliefs of GHB users. A total of 51 people, 30 men and 21 women, mean age of 31.1±7.6 years (range 18 – 52 years), who report having used GHB for an average of 4.3±2.5 years (range 1–11 years), were interviewed in 10 separate groups held in 2004. This paper discusses broadly the general experience of the GHB ‘high,’ major perceived benefits including sexual responses to the drug, perceived risks and dangers of ingestion, co-ingestion, and various contexts of use. The paper concludes with a discussion of the implications drawn from this information for clinicians treating patients who use GHB. PMID:17703706

  6. [Gamma-hydroxybutyric acid (GHB) dependence and the GHB withdrawal syndrome: diagnosis and treatment].

    PubMed

    van Noorden, Martijn S; Kamal, Rama; de Jong, Cor A J; Vergouwen, A C M Ton; Zitman, Frans G

    2010-01-01

    Gamma-hydroxybutyric acid (GHB) is a neurotransmitter that occurs naturally in the brain and is increasingly being used as a 'party drug' because of its relaxing and euphoria-inducing effects. GHB has a limited medical use in the treatment of narcolepsy. GHB-intoxications occur often in non-medical use, and generally result in a coma of short duration. GHB use several times a day can lead to tolerance and dependence. After sudden cessation or reduction of intensive GHB use, a severe withdrawal syndrome may occur with symptoms varying from tremor, anxiety and agitation to autonomic instability, hallucinations and delirium. Treatment of the GHB withdrawal syndrome consists of supportive care and benzodiazepines, often in high doses. The controlled detoxification of GHB using pharmaceutical GHB in an adjusted dose is currently being investigated in the Netherlands. There is no literature concerning the treatment of patients following GHB intoxication or after detoxification.

  7. BEHAVIORAL EFFECTS OF GAMMA-HYDROXYBUTYRATE (GHB) IN HUMANS

    PubMed Central

    Oliveto, Alison; Gentry, W. Brooks; Pruzinsky, Rhonda; Gonsai, Kishorchandra; Kosten, Thomas R.; Martell, Bridget; Poling, James

    2010-01-01

    Despite the therapeutic use and abuse potential of gamma-hydroxybutyrate (GHB or Xyrem), relatively few studies have examined the behavioral effects of GHB in humans under controlled laboratory conditions. Thus, this eight-session study examined in 10 non substance-abusing volunteers the behavioral effects of GHB at each of the following doses: 0, 0.32, 0.56, 0.75, 1.0, 1.8, 2.4, 3.2 g/70 kg, p.o.. Order of dose testing was random, except that the first two participants received active doses in ascending order and 2.4 g/70 kg was always tested before 3.2 g/70 kg. Prior to drug administration and at several post-drug time points, self-report, observer-report, physiological, and psychomotor performance measures were obtained. Analyses based on area under the curve showed that GHB produced dose-related increases in subjective ratings of sedative-like, stimulant-like, positive mood, and dissociative effects, but no changes in psychomotor performance measures or blood pressure. Analyses based on peak effects generally showed dose-related increases in ratings indicating sedative-like, dissociative, and drug liking, although some measures showed U-shaped dose-related changes. These initial findings suggest that GHB at doses of 0.32–3.2 g/70 kg produces dissociative, sedating and some stimulant-like effects in humans without a history of sedative abuse. PMID:20526195

  8. Gamma-hydroxybutyrate (GHB): a scoping review of pharmacology, toxicology, motives for use, and user groups.

    PubMed

    Brennan, Rebekah; Van Hout, Marie Claire

    2014-01-01

    Gamma hydroxybutyrate (GHB) is a central nervous system depressant with euphoric and relaxant effects. Documentation of GHB prevalence and the underreporting of abuse remains problematic, given the availability of GHB and its precursors γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) and the ease of synthesis from kits available on the Internet. The continued abuse of and dependence on GHB, and associated fatalities, present an on-going public health problem. As the drug GHB remains an underresearched topic, a scoping review was chosen as a technique to map the available literature into a descriptive summarized account. PRISMA was used to assist in data retrieval, with subsequent data charting into three key themes (pharmacology and toxicology, outcomes, and user groups). Administered orally, GHB is dose-dependent and popular for certain uses (therapeutic, body enhancement, sexual assault) and amongst user sub groups (recreational party drug users, homosexual men). Despite the low prevalence of use in comparison to other club drugs, rising abuse of the drug is associated with dependence, withdrawal, acute toxicity, and fatal overdose. Clinical diagnosis and treatment is complicated by the co-ingestion of alcohol and other drugs. Limitations of the scoping review and potential for further research and harm reduction initiatives are discussed.

  9. Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem): differences in characteristics and misuse.

    PubMed

    Carter, Lawrence P; Pardi, Daniel; Gorsline, Jane; Griffiths, Roland R

    2009-09-01

    There are distinct differences in the accessibility, purity, dosing, and misuse associated with illicit gamma-hydroxybutyrate (GHB) compared to pharmaceutical sodium oxybate. Gamma-hydroxybutyrate sodium and sodium oxybate are the chemical and drug names, respectively, for the pharmaceutical product Xyrem (sodium oxybate) oral solution. However, the acronym GHB is also used to refer to illicit formulations that are used for non-medical purposes. This review highlights important differences between illicit GHB and sodium oxybate with regard to their relative abuse liability, which includes the likelihood and consequences of abuse. Data are summarized from the scientific literature; from national surveillance systems in the U.S., Europe, and Australia (for illicit GHB); and from clinical trials and post-marketing surveillance with sodium oxybate (Xyrem). In the U.S., the prevalence of illicit GHB use, abuse, intoxication, and overdose has declined from 2000, the year that GHB was scheduled, to the present and is lower than that of most other licit and illicit drugs. Abuse and misuse of the pharmaceutical product, sodium oxybate, has been rare over the 5 years since its introduction to the market, which is likely due in part to the risk management program associated with this product. Differences in the accessibility, purity, dosing, and misuse of illicit GHB and sodium oxybate suggest that risks associated with illicit GHB are greater than those associated with the pharmaceutical product sodium oxybate.

  10. Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide.

    PubMed

    Petersen, Ida Nymann; Tortzen, Christian; Kristensen, Jesper Langgaard; Pedersen, Daniel Sejer; Breindahl, Torben

    2013-06-01

    Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3-6 h. In the search of improved detection methods, the existence in vivo of a glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards of GHB-GLUC and a deuterated analogue for chromatography were synthesized. Liquid chromatography and tandem mass spectrometry were used for targeted analysis in anonymous clinical urine samples (n = 50). GHB-GLUC was found in concentrations ranging from 0.11 to 5.0 µg/mL (mean: 1.3 ± 1.2 µg/mL). Thus far, this is the first report of a GHB glucuronide detected in biological samples. Given that glucuronides generally have longer half-life values than their corresponding free drugs, GHB-GLUC should theoretically be a biomarker of GHB intoxication. It is also proposed that the hitherto unexplained reports of elevated GHB concentrations in some biological samples, which has caused the setting of a relatively high cutoff value (10 µg/mL), represent total GHB measurements (sum of free GHB and actively chemically hydrolyzed GHB-GLUC). To address these challenges, the present study must be followed by comprehensive pharmacokinetic and stability studies after the controlled administration of GHB.

  11. High-Risk Behaviors and Hospitalizations Among Gamma Hydroxybutyrate (GHB) Users

    PubMed Central

    Kim, Susan Y.; Anderson, Ilene B.; Dyer, Jo Ellen; Barker, Judith C.; Blanc, Paul D.

    2008-01-01

    Introduction Little is known about behaviors linked to gamma hydroxybutyrate (GHB) morbidity. Methods We surveyed 131 GHB users, using logistic regression to test the associations between the high risk behaviors and hospital treatment for GHB (26 [20%] of subjects). Results Increased risk of GHB hospital treatment was associated with: co-ingestion of ethanol (OR 5.2; 95% CI 1.7–16), driving under the influence of GHB (OR 3.2; 95%, CI 1.3–7.8), use of GHB to treat withdrawal symptoms (OR 2.9; 95% CI 1.1–7.9), and co-ingestion of ketamine (OR 2.7; 95% CI 1.1–6.7). Conclusion Targeted prevention activities could focus on selected high-risk behaviors. PMID:17613970

  12. A Web-Based Study of Gamma Hydroxybutyrate (GHB): Patterns, Experiences, and Functions of Use

    PubMed Central

    Stein, LAR; Lebeau, Rebecca; Clair, Mary; Martin, Rosemarie; Bryant, Monte; Storti, Susan; Monti, Peter

    2011-01-01

    GHB (gamma hydroxybutyrate) was developed as a general anesthetic. Due to dosing difficulty and side effects, regular use was discontinued. Medical uses include treating sleep and alcohol disorders. In the 1990s, it was promoted as a supplement and taken to improve mood and sex. GHB and its analogs (gamma butyrolactone and butanediol) were widely available until federal regulations were put into effect with mounting evidence of adverse events. This survey (N = 61) study was conducted to assess patterns, experiences, and functions of use. Much of what is understood regarding GHB treatment is based on hospital case studies for overdose and withdrawal. Not enough is known about prevention, reducing use and associated problems, or relapse. We know little about specific drug effect expectancies, triggers, coping skills, and consequences of use (positive/negative). While the drug treatment literature has a wealth of information to draw upon, GHB-specific information may greatly assist relapse prevention. PMID:21175918

  13. GHB

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness GHB KidsHealth > For Teens > GHB A A A What's ... How Can Someone Quit? Avoiding GHB What Is GHB? GHB is short for gamma hydroxybutyrate. It's a ...

  14. Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication.

    PubMed

    Ferrara, S D; Tedeschi, L; Frison, G; Rossi, A

    1995-05-01

    The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication.

  15. Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse

    PubMed Central

    Carter, Lawrence P.; Pardi, Daniel; Gorsline, Jane; Griffiths, Roland R.

    2009-01-01

    There are distinct differences in the accessibility, purity, dosing, and misuse associated with illicit gamma-hydroxybutyrate (GHB) compared to pharmaceutical sodium oxybate. Gamma-hydroxybutyrate sodium and sodium oxybate are the chemical and drug names, respectively, for the pharmaceutical product Xyrem® (sodium oxybate) oral solution. However, the acronym GHB is also used to refer to illicit formulations that are used for non-medical purposes. This review highlights important differences between illicit GHB and sodium oxybate with regard to their relative abuse liability, which includes the likelihood and consequences of abuse. Data are summarized from the scientific literature; from national surveillance systems in the U.S., Europe, and Australia (for illicit GHB); and from clinical trials and post-marketing surveillance with sodium oxybate (Xyrem). In the U.S., the prevalence of illicit GHB use, abuse, intoxication, and overdose has declined from 2000, the year that GHB was scheduled, to the present and is lower than that of most other licit and illicit drugs. Abuse and misuse of the pharmaceutical product, sodium oxybate, has been rare over the 5 years since its introduction to the market, which is likely due in part to the risk management program associated with this product. Differences in the accessibility, purity, dosing, and misuse of illicit GHB and sodium oxybate suggest that risks associated with illicit GHB are greater than those associated with the pharmaceutical product sodium oxybate. PMID:19493637

  16. Fatal Combination with 3-Methylmethcathinone (3-MMC) and Gamma-Hydroxybutyric Acid (GHB).

    PubMed

    Jamey, Carole; Kintz, Pascal; Martrille, Laurent; Raul, Jean-Sébastien

    2016-09-01

    We reported the case of 69-year-old man who was discovered dead at a friend's home. 3-Methylmethcathinone (3-MMC) and poppers (alkyl nitrites) were found at the scene by the police. Autopsy specimens including peripheral and cardiac blood, urine, gastric content, bile and hair were sent to our laboratory to document a possible death involving abuse of drugs. Routine toxicological analysis was performed with gas chromatography with flame ionization detection (GC-FID), high performance liquid chromatography-diode array detection (HPLC-DAD), headspace gas chromatography-mass spectrometry (HS-GC-MS), gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)-MS. After liquid-liquid extraction at alkaline pH, 3-MMC was identified with GC-MS (to allow the discrimination with 4-MMC) and quantified with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-MS with the two following transitions: m/z 178.1 > 160 and 178.1 > 144.9. Gamma-hydroxybutyric acid (GHB) was analyzed by GC-MS for fluids and GC-MS-MS for hair. Toxicological analysis in peripheral blood revealed the presence of 3-MMC (0.33 mg/L), pseudoephedrine (0.03 mg/L) and GHB (576 mg/L). These molecules have also been found in other post-mortem fluids. Furthermore, testing for "poppers" by HS-GC-MS was negative. Hair analysis, without segmentation, demonstrated the presence of 3-MMC (206.7 ng/mg), pseudoephedrine (0.16 ng/mg) and GHB (96.3 ng/mg) and suggested a repeated consumption of these substances. However, one cannot exclude contamination by sweat during the agony period. Toxicological post-mortem results suggest a fatal combination of 3-MMC and GHB. Despite his age, the decedent was known to abuse drugs.

  17. [Gamma-hydroxybutyric acid (GHB): more than a date rape drug, a potentially addictive drug].

    PubMed

    Karila, Laurent; Novarin, Johanne; Megarbane, Bruno; Cottencin, Olivier; Dally, Sylvain; Lowenstein, William; Reynaud, Michel

    2009-10-01

    According to available information, GHB and its precursors--gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene characterized by the search for amplified sensations through the combination of electronic music, marathon dancing, and substance abuse. Evidence indicates that GHB/GHL is used particularly in some subpopulations and in places, such as in gay nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for its bodybuilding effects and in the 1990s as a recreational drug at music venues. In the same period, media coverage of the use of GHB in sexual assault (often referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction is a recognized clinical entity evidenced by severe withdrawal symptoms when the drug is abruptly discontinued after regular or chronic use. There is evidence that negative health and social consequences may occur in recreational and chronic users. Nonfatal overdoses and deaths related to GHB have been reported. These undesirable effects and especially the deaths appear to have prompted campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is being sold and used as a substitute for GHB.

  18. Monitoring of the interconversion of gamma-butyrolactone (GBL) to gamma hydroxybutyric acid (GHB) by Raman spectroscopy.

    PubMed

    Munshi, Tasnim; Brewster, Victoria L; Edwards, Howell G M; Hargreaves, Michael D; Jilani, Shelina K; Scowen, Ian J

    2013-08-01

    Gamma-hydroxybutyric acid (GHB) is a drug-of-abuse that has recently become associated with drug-facilitated sexual assault, known as date rape. For this reason the drug is commonly found 'spiked' in alcoholic beverages. When GHB is in solution it may undergo conversion into the corresponding lactone, Gamma-butyrolactone (GBL). Studies have been carried out to determine the detection limits of GHB and GBL in various solutions by Raman spectroscopy and to monitor the interconversion of GHB and GBL in solution with different pH conditions and temperature. In this study, a portable Raman spectrometer was used to study the interconversion of GHB and GBL in water and ethanol solutions as a function of pH, time, and temperature. The aim of this was to determine the optimum pH range for conversion in order to relate this to the pH ranges that the drug is likely to be subjected to, first in spiked beverages and secondly after ingestion in the digestive system. The aim was also to identify a timescale for this conversion in relation to possible scenarios, for example if GHB takes a number of hours to convert to GBL, it is likely for the beverage to be ingested before esterification can take place. GHB and GBL were then spiked into a selection of beverages of known pH in order to study the stability of GHB and GBL in real systems.

  19. Novel high-affinity and selective biaromatic 4-substituted gamma-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies.

    PubMed

    Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte; Frydenvang, Karla; Dahl, Ivar F; Bräuner-Osborne, Hans; Brehm, Lotte; Frølund, Bente; Clausen, Rasmus P

    2008-12-25

    Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands.

  20. Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue - Differentiating between postmortem formation and antemortem intake.

    PubMed

    Thomsen, Ragnar; Rasmussen, Brian Schou; Johansen, Sys Stybe; Linnet, Kristian

    2017-03-01

    Gamma-hydroxybutyrate (GHB) is a recreational drug, a drug of abuse, as well as an endogenous molecule in mammals. The drug has become infamous as a tool for drug-facilitated sexual assault. GHB is found in low concentrations in living humans, while at postmortem the concentration of GHB rises due to fermentation processes. The endogenous nature of GHB leads to difficulty in interpretation of concentrations, as the source of GHB is not obvious. Postmortem brain and blood samples were collected from 221 individuals at autopsy. Of these, 218 were not suspected of having ingested GHB, while GHB intake was reported for the last three (cases A-C). Decomposition level was estimated and cases classified into no/minor and advanced decomposition. Brain samples were extracted from the frontal lobe; only gray matter from the cerebral cortex was used. Blood was drawn from the femoral vein. Brain samples were homogenized and diluted with water. Brain homogenates or femoral blood were then prepared using protein precipitation and GHB was quantified with UHPLC-MS/MS. For 189 cases where ingestion of GHB was not suspected and where no/minor decomposition had occurred the concentrations were in the range 4.8-45.4mg/kg (median 15.3mg/kg) in blood and not-detected to 9.8mg/kg (median 4.8mg/kg) in brain tissue. For case A, where intoxication with GHB was deemed to be the sole cause of death, the concentrations were 199 and 166mg/kg in blood and brain, respectively. For case B, where intoxication with GHB was a contributing factor of death, the respective concentrations were 142 and 78.4mg/kg. For case C, where GHB was ingested but the cause of death was opioid poisoning, the concentrations were 40.3 and 12.7mg/kg. The results demonstrate that postmortem-formed levels of GHB are much lower in brain than peripheral blood. Analysis of GHB in brain tissue thus provides for an improved capability to identify an exogenous source of GHB. By measuring GHB in brain tissue and employing a cut

  1. Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency.

    PubMed

    Johansen, S S; Wang, X; Sejer Pedersen, D; Pearl, P L; Roullet, J-B; Ainslie, G R; Vogel, K R; Gibson, K M

    2017-02-18

    Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD. We quantified GHB in hair derived from ten patients with SSADHD, and documented a significant negative age correlation. These findings are consistent with recent results in patient biological fluids, including plasma and red blood cells. These findings may provide additional insight into the developmental course of SSADHD (Jansen et al., J Inherit Metab Dis 39:795-800, 2016).

  2. Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.

    PubMed

    Lott, S; Musshoff, F; Madea, B

    2012-09-10

    There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected by police during road side testing for GHB. The samples subject to this study have already been found to be positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDEA). Analysis has been performed by LC/MS/MS in the multiple reaction monitoring (MRM) mode. Due to its polarity, chromatographic separation of GHB was achieved by a HILIC column. To differentiate endogenous and exogenous levels of GHB, a cut-off concentration of 4μg/ml was applied. Of the 196 samples, two have been found to be positive for GHB. Of these samples, one sample was also positive for amphetamine and one for MDMA. Whilst other amphetamine derivates were not detected in these samples, both samples were found to be positive for cannabinoids. These results suggest that co-consumption of GHB with amphetamine or ecstasy is relatively low (1%) for the collective of this study.

  3. Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?

    PubMed

    Brown, Andrew J

    2007-01-01

    Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse.

  4. Gamma-hydroxybutyrate (GHB) induces cognitive deficits and affects GABAB receptors and IGF-1 receptors in male rats.

    PubMed

    Johansson, Jenny; Grönbladh, Alfhild; Hallberg, Mathias

    2014-08-01

    In recent years, the abuse of the club drug gamma-hydroxybutyrate (GHB) has become increasingly popular among adolescents. The drug induces euphoria but can also result in sedation, anaesthesia as well as short-term amnesia. In addition, the abuse of GHB causes cognitive impairments and the mechanism by which GHB induces these impairments is not clarified. The present study investigates the impact of GHB treatment on spatial learning and memory using a water maze (WM) test in rats. Furthermore, the behavioural data is combined with an autoradiographic analysis of the GABAB and the IGF-1 receptor systems. The results demonstrate that the animals administered with GHB display an impaired performance in the WM test as compared to controls. In addition, significant alterations in GABAB and IGF-1 receptor density as well as GABAB receptor functionality, were observed in several brain regions associated with cognitive functions e.g. hippocampus. To conclude, our findings suggest that GHB treatment can affect spatial learning and memory, and that this outcome at least to some extent is likely to involve both GABAB and IGF-1 receptors.

  5. The Impact of Gamma Hydroxybutyrate (GHB) Legal Restrictions on Patterns of Use: Results from an International Survey.

    PubMed

    Anderson, Ib; Kim-Katz, Sy; Dyer, Je; Blanc, Pd

    2010-10-01

    AIMS: To conduct an Internet-based survey of GHB use, identifying differences by respondent residence. METHODS: We recruited GHB-knowledgeable persons via "social networking Internet sites." Individuals (n=314) or groups (n=66) were approached based on GHB-use testimonials. DATA COLLECTED: location, use, reason for cessation (if applicable). FINDINGS: We recruited 155 GHB users. U.S. respondents (53 of 70; 76%) compared to non-U.S. respondents (38 of 85; 45%) were older and more highly educated (p<0.05) but manifest a 3-fold greater adjusted odds of GHB cessation (Odds Ratio [OR] 3.1; 95% CI 1.4-6.9; p < 0.05). Of the 80 respondents stating reason for cessation, 36 (45%) cited legal risk, price, or access; 44 (55%) cited health or related concerns. U.S. compared to non-U.S. respondents more frequently invoked legal and related concerns (OR 2.5; 95% CI 0.99-6.3; p=0.05). In a nested analysis, narrowly stated legal (n=4/5 U.S.) versus health (n=6/18 U.S.) reasons differed by location (p=0.048, one-tailed). CONCLUSIONS: In the U.S., where GHB has stricter legal penalties, GHB cessation is more likely, with legal and related reasons more commonly invoked for cessation. These findings support a link between declining U.S. GHB abuse and more stringent restrictions; although other un-assessed factors may also explain this association. The Impact of Gamma Hydroxybutyrate (GHB) Legal Restrictions on Patterns of Use: Results from an International Survey.

  6. The Impact of Gamma Hydroxybutyrate (GHB) Legal Restrictions on Patterns of Use: Results from an International Survey

    PubMed Central

    Anderson, IB; Kim-Katz, SY; Dyer, JE; Blanc, PD

    2009-01-01

    Aims To conduct an Internet-based survey of GHB use, identifying differences by respondent residence. Methods We recruited GHB-knowledgeable persons via “social networking Internet sites.” Individuals (n=314) or groups (n=66) were approached based on GHB-use testimonials. Data collected location, use, reason for cessation (if applicable). Findings We recruited 155 GHB users. U.S. respondents (53 of 70; 76%) compared to non-U.S. respondents (38 of 85; 45%) were older and more highly educated (p<0.05) but manifest a 3-fold greater adjusted odds of GHB cessation (Odds Ratio [OR] 3.1; 95% CI 1.4–6.9; p < 0.05). Of the 80 respondents stating reason for cessation, 36 (45%) cited legal risk, price, or access; 44 (55%) cited health or related concerns. U.S. compared to non-U.S. respondents more frequently invoked legal and related concerns (OR 2.5; 95% CI 0.99–6.3; p=0.05). In a nested analysis, narrowly stated legal (n=4/5 U.S.) versus health (n=6/18 U.S.) reasons differed by location (p=0.048, one-tailed). Conclusions In the U.S., where GHB has stricter legal penalties, GHB cessation is more likely, with legal and related reasons more commonly invoked for cessation. These findings support a link between declining U.S. GHB abuse and more stringent restrictions; although other un-assessed factors may also explain this association. The Impact of Gamma Hydroxybutyrate (GHB) Legal Restrictions on Patterns of Use: Results from an International Survey PMID:20953310

  7. Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs.

    PubMed

    Andresen-Streichert, Hilke; Jensen, P; Kietzerow, J; Schrot, M; Wilke, N; Vettorazzi, E; Mueller, A; Iwersen-Bergmann, S

    2015-01-01

    When interpreting gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens, a possible increase in GHB concentrations because of post-mortem generation must be considered. In this study, endogenous GHB concentrations in post-mortem biological fluids were investigated. Additionally, we review post-mortem GHB concentrations already published in the literature. Heart and peripheral blood samples, cerebrospinal fluid, urine, and vitreous humor were collected from 64 autopsies in subjects where the cause of death excluded GHB exposure. Sample analysis was carried out either on the day of autopsy or later after immediate freezing and storage at -20 °C. GHB concentrations in venous blood samples (n = 61) were <0.6-28.7 mg/L (mean 11.9 mg/L; median 10.6 mg/L), <0.6-65.3 mg/L (mean 15.2 mg/L; median 12.8 mg/L) in heart blood (n = 56), <0.6-25.1 mg/L (mean 6.0 mg/L; median 3.8 mg/L) in urine (n = 50), <0.6-39.0 mg/L (mean 9.6 mg/L; median 7.5 mg/L), in vitreous humor (n = 54), and <0.6-24.0 mg/L (mean 4.2 mg/L; median 3.2 mg/L) in cerebrospinal fluid (n = 52). There was no significant difference between GHB concentrations in cases where there were signs of beginning putrefaction at the time of autopsy (n = 9) and cases without obvious signs of putrefaction. In one case with advanced putrefaction, the GHB concentration in venous blood was 32.7 mg/L. In conclusion, for post-mortem venous blood, urine, and cerebrospinal fluid, an interpretative cut-off of 30 mg/L for GHB concentrations is suggested in cases where GHB analysis is conducted on the day of sample collection at autopsy or if samples have been stored at -20 °C immediately after collection.

  8. Comparative study of equimolar doses of gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) on catalepsy after acute and chronic administration.

    PubMed

    Towiwat, Pasarapa; Phattanarudee, Siripan; Maher, Timothy J

    2013-01-01

    Gamma-hydroxybutyrate (GHB), and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) are known drugs of abuse. The ability of acute and chronic administration of equimolar doses of GHB (200mg/kg), 1,4-BD (174mg/kg) and GBL (166mg/kg) to produce catalepsy in male Swiss Webster mice was examined. GHB, 1,4-BD, GBL produced catalepsy when injected acutely. Drug treatment was then continued for 14days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naïve mice. Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve (AUC) of catalepsy versus time (min-sec) on days 6 (678±254), 14 (272±247), which were less than those on day 1 (1923±269). However, less tolerance was seen from GBL or 1,4-BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1. In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1,4-BD and GBL shared only some of the in vivo effects of GHB. The rate of metabolic conversion of 1,4-BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs.

  9. Risk assessment of gamma-hydroxybutyric acid (GHB) in the Netherlands.

    PubMed

    van Amsterdam, Jan G C; van Laar, Margriet; Brunt, Tibor M; van den Brink, Wim

    2012-06-01

    The Dutch Minister of Health requested the Coordination point Assessment and Monitoring new drugs (CAM) to re-assess the overall risk of GHB. The present paper is a extended redraft of a state of art report used in the risk evaluation procedure. The prevalence of GHB use is low, but the relative proportion of GHB intoxications compared to other illicit drugs is high resulting in a substantial number of GHB related incidents. In recent years the number of GHB intoxications has increased because many inexperienced users seemed unaware of the potential adverse effects, like 'passing out' upon overdosing, a condition where the user is unconsciousness (or comatose) for several hours. The dependence potential of frequent GHB use is now judged by the CAM to be rather high, but users appear not well informed about this risk. In the Netherlands, last month prevalence of GHB use is relatively low (0.2%) and treatment demand is limited (524 of a total of 76,295 referrals to the addiction treatment services in 2010). So far, no public nuisance or criminality associated with GHB use has been reported. The CAM estimated the overall risk potential of GHB use as moderate to high. The Dutch Minister of Health endorsed this conclusion and decided to upgrade GHB to Schedule I (hard drugs) of the Dutch Opium Act.

  10. A critical evaluation of the gamma-hydroxybutyrate (GHB) model of absence seizures.

    PubMed

    Venzi, Marcello; Di Giovanni, Giuseppe; Crunelli, Vincenzo

    2015-02-01

    Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the γ-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs.

  11. Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples.

    PubMed

    Busardò, Francesco Paolo; Bertol, Elisabetta; Vaiano, Fabio; Baglio, Giovanni; Montana, Angelo; Barbera, Nunziata; Zaami, Simona; Romano, Guido

    2014-10-01

    Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse with numerous names. It has also been involved in various instances of drug-facilitated sexual assault due to its potential incapacitating effects. The first aim of this paper is to measure the post-mortem concentration of endogenous GHB in whole blood and urine samples of 30 GHB free-users, who have been divided according to the post-mortem interval (PMI) in three groups (first group: 24-36h; second group: 37-72h; third group: 73-192h), trying to evaluate the role of PMI in affecting post mortem levels. Second, the Authors have evaluated the new formation of GHB in vitro in blood and urine samples of the three groups, which have been stored at -20°C, 4°C and 20°C over a period of one month. The concentrations were measured by GC-MS after liquid-liquid extraction according to the method validated and published by Elliot (For. Sci. Int., 2003). For urine samples, GHB concentrations were creatinine-normalized. In the first group the GHB mean concentration measured after autopsy was: 2.14mg/L (range 0.54-3.21mg/L) in blood and 3.90mg/g (range 0.60-4.81mg/g) in urine; in the second group it was: 5.13mg/L (range 1.11-9.60mg/L) in blood and 3.93mg/g (range 0.91-7.25mg/g) in urine; in the third group it was: 11.8mg/L (range 3.95-24.12mg/L) in blood and 9.83mg/g (range 3.67-21.90mg/g) in urine. The results obtained in blood and urine samples showed a statistically significant difference among groups (p<0.001) in the first analysis performed immediately after autopsy. Throughout the period of investigation up to 4 weeks, the comparison of storage temperatures within each group showed in blood and urine samples a mean difference at 20°C compared to -20°C not statistically significant at the 10% level. These findings allow us to affirm that the PMI strongly affects the post mortem production of GHB in blood and urine samples. Regarding the new formation of

  12. Carbon isotopic ratio analysis by gas chromatography/combustion/isotope ratio mass spectrometry for the detection of gamma-hydroxybutyric acid (GHB) administration to humans.

    PubMed

    Saudan, Christophe; Augsburger, Marc; Mangin, Patrice; Saugy, Martial

    2007-01-01

    Since GHB (gamma-hydroxybutyric acid) is naturally produced in the human body, clinical and forensic toxicologists must be able to discriminate between endogenous levels and a concentration resulting from exposure. To suggest an alternative to the use of interpretative concentration cut-offs, the detection of exogenous GHB in urine specimens was investigated by means of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). GHB was isolated from urinary matrix by successive purification on Oasis MCX and Bond Elute SAX solid-phase extraction (SPE) cartridges prior to high-performance liquid chromatography (HPLC) fractioning using an Atlantis dC18 column eluted with a mixture of formic acid and methanol. Subsequent intramolecular esterification of GHB leading to the formation of gamma-butyrolactone (GBL) was carried out to avoid introduction of additional carbon atoms for carbon isotopic ratio analysis. A precision of 0.3 per thousand was determined using this IRMS method for samples at GHB concentrations of 10 mg/L. The (13)C/(12)C ratios of GHB in samples of subjects exposed to the drug ranged from -32.1 to -42.1 per thousand, whereas the results obtained for samples containing GHB of endogenous origin at concentration levels less than 10 mg/L were in the range -23.5 to -27.0 per thousand. Therefore, these preliminary results show that a possible discrimination between endogenous and exogenous GHB can be made using carbon isotopic ratio analyses.

  13. Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication

    PubMed Central

    Kim, Susan Y.; Barker, Judith C.; Anderson, Ilene B.; Dyer, Jo Ellen; Earnest, Gillian; Blanc, Paul D.

    2009-01-01

    We adapted and tested a previously published questionnaire battery eliciting sensory and cognitive symptoms during (acute) and immediately after (post-acute) GHB intoxication. Studying 125GHBusers, we assessed the instrument’s internal consistency using Cronbach’s alpha (CA) and responsiveness to change comparing acute and post-acute symptoms. The final 14-item battery demonstrated good internal consistency (CA ≥ 0.85, both acute and post-acute). The median symptom score (possible range 0–64) was 30 (acute) and 6 (post-acute; difference p < 0.001). This modified substance-specific symptom battery, which is easily administered, demonstrated excellent performance characteristics. It can be used to study GHB and, potentially, related drugs of abuse. PMID:18612887

  14. Incidence of craving for and abuse of gamma-hydroxybutyric acid (GHB) in different populations of treated alcoholics: an open comparative study.

    PubMed

    Caputo, F; Francini, S; Stoppo, M; Lorenzini, F; Vignoli, T; Del Re, A; Comaschi, C; Leggio, L; Addolorato, G; Zoli, G; Bernardi, M

    2009-11-01

    Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of alcohol dependence. The aim of our study was to investigate the incidence of craving for and abuse of GHB in 47 patients enrolled and divided into four groups: group A (pure alcoholics), group B (alcoholics with a sustained full remission from cocaine dependence), group C (alcoholics with a sustained full remission from heroin dependence) and group D (alcoholics in a methadone maintenance treatment [MMT] programme). All patients were treated with an oral dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB was statistically significant higher in group B than in group A (P < 0.001), C (P = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of GHB proved to be statistically significant higher in group B than in group A (P < 0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P < 0.05). Thus, the administration of GHB in alcoholics with a sustained full remission from heroin or cocaine dependence is not recommended; however, this should not discourage physicians from using GHB for the treatment of pure alcoholics or alcohol dependents following a MMT.

  15. gamma-Hydroxybutyrate (GHB) induces GABA(B) receptor independent intracellular Ca2+ transients in astrocytes, but has no effect on GHB or GABA(B) receptors of medium spiny neurons in the nucleus accumbens.

    PubMed

    Molnár, T; Antal, K; Nyitrai, G; Emri, Z

    2009-08-18

    We report on cellular actions of the illicit recreational drug gamma-hydroxybutyrate (GHB) in the brain reward area nucleus accumbens. First, we compared the effects of GHB and the GABA(B) receptor agonist baclofen. Neither of them affected the membrane currents of medium spiny neurons in rat nucleus accumbens slices. GABAergic and glutamatergic synaptic potentials of medium spiny neurons, however, were reduced by baclofen but not GHB. These results indicate the lack of GHB as well as postsynaptic GABA(B) receptors, and the presence of GHB insensitive presynaptic GABA(B) receptors in medium spiny neurons. In astrocytes GHB induced intracellular Ca(2+) transients, preserved in slices from GABA(B) receptor type 1 subunit knockout mice. The effects of tetrodotoxin, zero added Ca(2+) with/without intracellular Ca(2+) store depletor cyclopiazonic acid or vacuolar H-ATPase inhibitor bafilomycin A1 indicate that GHB-evoked Ca(2+) transients depend on external Ca(2+) and intracellular Ca(2+) stores, but not on vesicular transmitter release. GHB-induced astrocytic Ca(2+) transients were not affected by the GHB receptor-specific antagonist NCS-382, suggesting the presence of a novel NCS-382-insensitive target for GHB in astrocytes. The activation of astrocytes by GHB implies their involvement in physiological actions of GHB. Our findings disclose a novel profile of GHB action in the nucleus accumbens. Here, unlike in other brain areas, GHB does not act on GABA(B) receptors, but activates an NCS-382 insensitive GHB-specific target in a subpopulation of astrocytes. The lack of either post- or presynaptic effects on medium spiny neurons in the nucleus accumbens distinguishes GHB from many drugs and natural rewards with addictive properties and might explain why GHB has only a weak reinforcing capacity.

  16. Report on the analysis of common beverages spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) using NMR and the PURGE solvent-suppression technique.

    PubMed

    Lesar, Casey T; Decatur, John; Lukasiewicz, Elaan; Champeil, Elise

    2011-10-10

    In forensic evidence, the identification and quantitation of gamma-hydroxybutyric acid (GHB) in "spiked" beverages is challenging. In this report, we present the analysis of common alcoholic beverages found in clubs and bars spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL). Our analysis of the spiked beverages consisted of using (1)H NMR with a water suppression method called Presaturation Utilizing Relaxation Gradients and Echoes (PURGE). The following beverages were analyzed: water, 10% ethanol in water, vodka-cranberry juice, rum and coke, gin and tonic, whisky and diet coke, white wine, red wine, and beer. The PURGE method allowed for the direct identification and quantitation of both compounds in all beverages except red and white wine where small interferences prevented accurate quantitation. The NMR method presented in this paper utilizes PURGE water suppression. Thanks to the use of a capillary internal standard, the method is fast, non-destructive, sensitive and requires no sample preparation which could disrupt the equilibrium between GHB and GBL.

  17. Identification of the date-rape drug GHB and its precursor GBL by Raman spectroscopy.

    PubMed

    Brewster, Victoria L; Edwards, Howell G M; Hargreaves, Michael D; Munshi, Tasnim

    2009-01-01

    Gamma hydroxybutyric acid (GHB), also known as 'liquid ecstasy', has recently become associated with drug-facilitated sexual assaults, known colloquially as 'date rape', due to the ability of the drug to cause loss of consciousness. The drug is commonly found 'spiked' into alcoholic beverages, as alcohol increases its sedative effects. Gamma hydroxybutyric acid and the corresponding lactone gamma-butyrolactone (GBL) will reach an equilibrium in solution which favours the lactone in basic conditions and GHB in acidic conditions (less than pH 4). Therefore, we have studied both GHB and GBL, as a mildly acidic beverage 'spiked' with GHB will contain both GHB and GBL. We report the analysis of GHB as a sodium salt and GBL, its precursor, using bench-top and portable Raman spectroscopy. It has been demonstrated that we are able to detect GHB and GBL in a variety of containers including colourless and amber glass vials, plastic vials and polythene bags. We have also demonstrated the ability to detect both GBL and GHB in a range of liquid matrices simulating 'spiked' beverages.

  18. Sedative and hypothermic effects of gamma-hydroxybutyrate (GHB) in rats alone and in combination with other drugs: assessment using biotelemetry.

    PubMed

    van Nieuwenhuijzen, Petra S; McGregor, Iain S

    2009-08-01

    The recreational drug gamma-hydroxybutyrate (GHB) has euphoric effects and can induce sedation and body temperature changes. GHB is frequently combined with other recreational drugs although these interactions are not well characterised. The present study used biotelemetry to provide a fine-grained analysis of the effects of GHB on body temperature and locomotor activity in freely moving rats, and investigated interactions between GHB and 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH) and various antagonist drugs. GHB (1000mg/kg) caused profound sedation for more than 2h and a complex triphasic effect on body temperature: an initial hypothermia (5-40min), followed by hyperthermia (40-140min), followed again by hypothermia (140-360min). A lower GHB dose (500mg/kg) also caused sedation but only a hypothermic effect that lasted up to 6h. The dopamine D(1) receptor antagonist SCH 23390 (1mg/kg), the opioid antagonist naltrexone (1mg/kg), the benzodiazepine antagonist flumazenil (10mg/kg), and the 5-HT(2A/2C) receptor antagonist ritanserin (1mg/kg) did not prevent the overall sedative or body temperature effects of GHB (1000mg/kg). However the GABA(B) antagonist SCH 50911 (50mg/kg) prevented the hyperthermia induced by GHB (1000mg/kg). Repeated daily administration of GHB (1000mg/kg) produced tolerance to the sedative and hyperthermic effects of the drug and cross-tolerance to the sedative effects of the GABA(B) receptor agonist baclofen (10mg/kg). A high ambient temperature of 28 degrees C prevented the hypothermia obtained with GHB (500mg/kg) at 20 degrees C, while GHB (500mg/kg) reduced the hyperthermia and hyperactivity produced by co-administered doses of MDMA (5mg/kg) or METH (1mg/kg) at 28 degrees C. These results further confirm a role for GABA(B) receptors in the hypothermic and sedative effects of GHB and show an interaction between GHB and MDMA, and GHB and METH, that may be relevant to the experience of recreational users who mix these

  19. Gamma-Hydroxybutyrate (GHB)

    MedlinePlus

    ... Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury Rehabilitation Emotional Well- ...

  20. Gamma-butyrolactone (GBL) disruption of passive avoidance learning in the day-old chick appears to be due to its effect on GABAB not gamma-hydroxybutyric [corrected] acid (GHB) receptors.

    PubMed

    Sherry, Joanne M; Hazi, Agnes; Hale, Mathew W; Milsome, Sarah L; Crowe, Simon F

    2009-02-11

    Gamma-butyrolactone (GBL) is a prodrug to gamma-hydroxybutyric acid (GHB) and metabolises to GHB when ingested. Discrimination stimulus studies report generalisation of effects of GHB to GBL. While amnesia is one of the most commonly reported symptoms of GHB's ingestion in human users, as yet few studies have examined this effect. Although an endogenous GHB specific receptor is present in the brain, several studies have indicated that the clinical effects of exogenous doses of GBL/GHB are due to its action on GABA(B) receptors rather than on the GHB receptor. In this series of studies, New Hampshire x White leghorn cockerels were trained using a modified version of the passive avoidance learning task. Subcutaneous injections of GBL induced a memory deficit by 10 min post-training, which persisted for at least 24 h. No effect on memory was seen with administration of the specific GHB agonist NCS-356 (gamma-p-chlorophenyl-trans-4-hydroxycrotonate). The GBL-induced memory deficit appeared similar to the deficit produced by baclofen, where the antagonist facilitated learning. Additionally, GBL-induced memory deficit was ameliorated by application of a GABA(B) antagonist. The results support the hypothesis that GBL exerts its influence on memory via the GABA(B) receptor rather than by the specific GHB receptor.

  1. GHB - Gamma-Hydroxybutyric Acid

    MedlinePlus

    ... Drug Free: Red Ribbon Week Oct. 23-31 Watch DEA National Red Ribbon Rally Video: Red Ribbon Week Red Ribbon Resolution Introduced In The House Of Representatives DEA Red Ribbon Week Patch Program National Heroin and ... What is it? Prescribed as Xyrem, it is also known as the “date rape drug." It comes in a liquid or as ...

  2. Source inference of exogenous gamma-hydroxybutyric acid (GHB) administered to humans by means of carbon isotopic ratio analysis: novel perspectives regarding forensic investigation and intelligence issues.

    PubMed

    Marclay, François; Saudan, Christophe; Vienne, Julie; Tafti, Mehdi; Saugy, Martial

    2011-05-01

    γ-Hydroxybutyric acid (GHB) is an endogenous short-chain fatty acid popular as a recreational drug due to sedative and euphoric effects, but also often implicated in drug-facilitated sexual assaults owing to disinhibition and amnesic properties. Whilst discrimination between endogenous and exogenous GHB as required in intoxication cases may be achieved by the determination of the carbon isotope content, such information has not yet been exploited to answer source inference questions of forensic investigation and intelligence interests. However, potential isotopic fractionation effects occurring through the whole metabolism of GHB may be a major concern in this regard. Thus, urine specimens from six healthy male volunteers who ingested prescription GHB sodium salt, marketed as Xyrem(®), were analysed by means of gas chromatography/combustion/isotope ratio mass spectrometry to assess this particular topic. A very narrow range of δ(13)C values, spreading from -24.81‰ to -25.06‰, was observed, whilst mean δ(13)C value of Xyrem(®) corresponded to -24.99‰. Since urine samples and prescription drug could not be distinguished by means of statistical analysis, carbon isotopic effects and subsequent influence on δ(13)C values through GHB metabolism as a whole could be ruled out. Thus, a link between GHB as a raw matrix and found in a biological fluid may be established, bringing relevant information regarding source inference evaluation. Therefore, this study supports a diversified scope of exploitation for stable isotopes characterized in biological matrices from investigations on intoxication cases to drug intelligence programmes.

  3. The mRNA expression of insulin-like growth factor-1 (Igf1) is decreased in the rat frontal cortex following gamma-hydroxybutyrate (GHB) administration.

    PubMed

    Brolin, Erika; Johansson, Jenny; Zelleroth, Sofia; Diwakarla, Shanti; Nyberg, Fred; Grönbladh, Alfhild; Hallberg, Mathias

    2017-02-26

    In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function. Sprague Dawley rats (n=36) were divided into three groups and administered either saline, GHB 50mg/kg or GHB 300mg/kg orally for seven days. The levels of Ghr, Igf1 and Igf2 gene transcripts were analyzed using qPCR in brain regions involved in cognition and dependence. The levels of IGF-1 in blood plasma were also determined using ELISA. The results demonstrated a significant down-regulation of Igf1 mRNA expression in the frontal cortex in high-dose treated rats. Moreover, a significant correlation between Igf1 and Ghr mRNA expression was found in the hippocampus, the frontal cortex, and the caudate putamen, indicating local regulation of the GH/IGF-1 axis. To summarize, the current study concludes that chronic GHB treatment influences gene expression of Ghr and Igf1 in brain regions involved in cognitive function.

  4. "Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndrome.

    PubMed

    Friedman, J; Westlake, R; Furman, M

    1996-02-01

    Gamma-hydroxybutyrate (GHB) is a naturally occurring GABA-like drug used illicitly by bodybuilders. Although there are reports of several cases of GHB abuse, with a variety of nervous system complications, we present the first case associated with a Wernicke-Korsakoff syndrome.

  5. Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for determination of GHB, precursors and metabolites in different specimens: Application to clinical and forensic cases.

    PubMed

    Busardò, Francesco Paolo; Kyriakou, Chrystalla; Marchei, Emilia; Pacifici, Roberta; Pedersen, Daniel Sejer; Pichini, Simona

    2017-04-15

    Gamma-hydroxybutyric acid (GHB) acts as a precursor and metabolite of the inhibitory central nervous system (CNS) neurotransmitter gamma-aminobutyric acid (GABA). Sodium salt of GHB has been used as a medication for narcolepsy and alcohol withdrawal. Moreover, GHB and its precursor gamma-butyrolactone (GBL), are illegal recreational drugs of abuse. A procedure based on ultra-high-performance liquid chromatography tandem mass spectrometry has been developed and validated in plasma, urine, cerebrospinal fluid and hair for acute and chronic exposure to GHB and in seized preparations coming from black market. In biological matrices, GHB was investigated together with its glucuronide (GHB-Gluc) as a potential marker of exposure, GABA as endogenous precursor and metabolite and GBL as eventual exogenous precursor. GBL was sought together with GHB in illegal preparations. Chromatographic separation was achieved at ambient temperature using a reverse-phase column and an isocratic elution with two solvents: 0.1% formic acid in water and pure methanol. Multiple reaction monitoring (MRM) was used. The method was linear for all analytes under investigation from limit of quantification (LOQ) to 500μgmL(-1) plasma, urine and cerebrospinal fluid, from LOQ to 100ngmg(-1) hair and from LOQ to 10mgmL(-1) illicit preparations with good correlation coefficients (r(2)=0.99) for all substances. Recovery of analytes under investigation was always higher than 75% and intra-assay and inter-assay precision and accuracy were always better than 15%. The validated method was then successfully applied to real specimens from either forensic (one post-mortem urine sample taken from a GHB fatal intoxication case) or clinical cases (cerebrospinal fluid, plasma and hair samples collected from narcoleptic patients under sodium oxybate treatment). Finally, illicit preparations, seized by police forces were also checked for GHB amount and eventual presence of prodrug GBL.

  6. Drug-facilitated sexual assault involving gamma-hydroxybutyric acid.

    PubMed

    Stillwell, Matthew E

    2002-09-01

    The first case involving an alleged sexual assault linked to the use of gamma-hydroxybutyric acid (GHB) in Oklahoma is reported. A-48-year-old Caucasian woman taking amitriptyline was known to have voluntarily ingested a sports drink containing a relaxing health product. She purportedly experienced unconsciousness that persisted for approximately 4 h. The toxicological testing on urine identified GHB, amitriptyline, and nortriptyline using a capillary Hewlett-Packard 6890 gas chromatograph coupled to a Hewlett-Packard 5973 mass selective detector (MSD). The GHB concentration in urine was 26.9 microg/mL. Urine concentrations of amitriptyline and nortriptyline were not determined. The analytical method used for identifying and quantitating GHB can be applied to matters of forensic interests.

  7. Safety and tolerability of gamma-hydroxybutyric acid in the treatment of alcohol-dependent patients.

    PubMed

    Beghè, F; Carpanini, M T

    2000-04-01

    Gamma-hydroxybutyric acid (GHB) has been in clinical use in Italy since 1991 for treatment of alcohol dependence. Results of phase III and phase IV studies have shown that the drug is effective and well tolerated in the treatment of alcohol withdrawal syndrome and in reducing alcohol consumption and alcohol craving. Pharmacosurveillance indicates that abuse of gamma-hydroxybutyric acid is a limited phenomenon in clinical settings when the drug is dispensed under strict medical surveillance and entrusted to a referring familiar member of the patient.

  8. Gamma hydroxybutyrate: an ethnographic study of recreational use and abuse.

    PubMed

    Lee, Steven J; Levounis, Petros

    2008-09-01

    Gamma hydroxybutyrate (GHB) is a psychoactive substance with complex neurophysiological activity and significant potential for abuse, addiction, and dangerous toxicity. In this study, a semistructured interview was administered to 17 subjects to investigate GHB use, including: manner of use; setting; positive and negative consequences; other drug history; and sexual practices. Respondents were overwhelmingly male, but otherwise had a broad demographic background. Settings varied from nightclubs to private use at home. There was significant variability in the drug obtained, which subjects found problematic because of the narrow therapeutic window and ease of accidental overdose. Common positive experiences included increased sexual desire, decreased sexual inhibitions, and decreased anxiety. Common negative consequences included oversedation, loss of consciousness, motor incoordination, and mental confusion. Nine subjects reported that they would use GHB again, some despite severe negative consequences. Although most subjects reported negative experiences, only three felt their use was problematic, and none sought treatment for GHB abuse or addiction. Subjects were highly drug-experienced, most commonly using MDMA, ketamine, cocaine, alcohol, and methamphetamine. Some reported that GHB could cause poor decision making in sexual situations. This effect has significant ramifications for issues such as date rape and control of sexually transmitted diseases, such as HIV.

  9. What You Need to Know about Drugs: GHB

    MedlinePlus

    ... Room? What You Need to Know About Drugs: GHB KidsHealth > For Kids > What You Need to Know About Drugs: GHB A A A en español Lo que necesitas saber sobre las drogas: El GHB What It Is: GHB (gamma hydroxybutyrate) is illegally ...

  10. Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD; BDO): A literature review with a focus on UK fatalities related to non-medical use.

    PubMed

    Corkery, John M; Loi, Barbara; Claridge, Hugh; Goodair, Christine; Corazza, Ornella; Elliott, Simon; Schifano, Fabrizio

    2015-06-01

    Misuse of gamma hydroxybutrate (GHB) and gamma butyrolactone (GBL) has increased greatly since the early 1990s, being implicated in a rising number of deaths. This paper reviews knowledge on GHB and derivatives, and explores the largest series of deaths associated with their non-medical use. Descriptive analyses of cases associated with GHB/GBL and 1,4-butanediol (1,4-BD) use extracted from the UK's National Programme on Substance Abuse Deaths database. From 1995 to September 2013, 159 GHB/GBL-associated fatalities were reported. Typical victims: White (92%); young (mean age 32 years); male (82%); with a drug misuse history (70%). Most deaths (79%) were accidental or related to drug use, the remainder (potential) suicides. GHB/GBL alone was implicated in 37%; alcohol 14%; other drugs 28%; other drugs and alcohol 15%. Its endogenous nature and rapid elimination limit toxicological detection. Post-mortem blood levels: mean 482 (range 0-6500; SD 758)mg/L. Results suggest significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, opiates, stimulants, and ketamine. More awareness is needed about risks associated with consumption.

  11. GHB, GBL and 1,4-BD addiction.

    PubMed

    Brunt, Tibor M; van Amsterdam, Jan G C; van den Brink, Wim

    2014-01-01

    A growing body of evidence shows that gamma-hydroxybutyric acid (GHB) is an addictive substance. Its precursors gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD) show the same properties and may pose even more risks due to different pharmacokinetics. There are indications that problematic GHB use is increasing in the European Union. This review investigates the existing literature on the neurochemistry of GHB and its precursors, their acute toxicity, addiction potential and withdrawal, the proposed molecular mechanism underlying addiction and the treatment of withdrawal and addiction. Current evidence shows that GHB and its precursors are highly addictive, both in humans and animals, probably through a GABAB receptor related mechanism. Severity of withdrawal symptoms can be considered as a medical emergency. Recent studies suggest that benzodiazepines are not very effective, showing a high treatment resistance, whereas detoxification with pharmaceutical GHB proved to be successful. However, relapse in GHB use is frequent and more research is warranted on relapse prevention. This might aid medical practitioners in the field and improve general understanding of the severity of addiction to GHB, GBL and 1,4-BD.

  12. Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

    PubMed

    Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior.

  13. GHB

    MedlinePlus

    ... tremors, and sweating. Many of GHB's long-term effects are still unknown, but some that are known are: problems sleeping breathing problems depression and other mental health issues memory problems continue Other Possible Problems Taking ...

  14. Baclofen antagonises intravenous self-administration of gamma-hydroxybutyric acid in mice.

    PubMed

    Fattore, L; Cossu, G; Martellotta, M C; Deiana, S; Fratta, W

    2001-07-20

    gamma-Hydroxybutyric acid (GHB) is a widely used recreational drug known to exert positive reinforcing effects in animals and humans. The GABA(B) receptor agonist baclofen has been proved to possess antimotivational effect and to inhibit alcohol, cocaine, heroin and nicotine intake. In the present study we evaluated the effect of baclofen on i.v. self-administration of GHB in drug-naive mice under a fixed-ratio (FR-1) schedule of reinforcement and nose-poking-like response as operandum. Results show that baclofen was able to completely prevent GHB seeking behaviour, decreasing the rate of responding to basal values, without showing any reinforcing properties when made contingent on nose-poking response. Our findings demonstrate that baclofen antagonises GHB i.v. self-administration, supporting an important role for the GABA(B) receptor in reward-related mechanisms underlying addictive behaviour.

  15. GHB Abuse Trends and Use in Drug-Facilitated Sexual Assault: Implications for Prevention.

    ERIC Educational Resources Information Center

    Hensley, Laura

    2003-01-01

    Gamma-hydroxybutyric acid (GHB) has become increasingly popular on the campuses of American colleges and universities. In this paper, the characteristics of GHB and the effects of both voluntary and involuntary abuse are described. Further, implications for prevention efforts related to involuntary GHB ingestion and GHB-facilitated rape are…

  16. Therapeutic intervention in mice deficient for succinate semialdehyde dehydrogenase (gamma-hydroxybutyric aciduria).

    PubMed

    Gupta, Maneesh; Greven, Rachel; Jansen, Erwin E W; Jakobs, Cornelis; Hogema, Boris M; Froestl, Wolfgang; Snead, O Carter; Bartels, Hilke; Grompe, Markus; Gibson, K Michael

    2002-07-01

    Therapeutic intervention for human succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) has been limited to vigabatrin (VGB). Pharmacologically, VGB should be highly effective due to 4-aminobutyrate-transaminase (GABA-transaminase) inhibition, lowering succinic semialdehyde and, thereby, gamma-hydroxybutyric acid (GHB) levels. Unfortunately, clinical efficacy has been limited. Because GHB possesses a number of potential receptor interactions, we addressed the hypothesis that antagonism of these interactions in mice with SSADH deficiency could lead to the development of novel treatment strategies for human patients. SSADH-deficient mice have significantly elevated tissue GHB levels, are neurologically impaired, and die within 4 weeks postnatally. In the current report, we compared oral versus intraperitoneal administration of VGB, CGP 35348 [3-aminopropyl(diethoxymethyl)phosphinic acid, a GABA(B) receptor antagonist], and the nonprotein amino acid taurine in rescue of SSADH-deficient mice from early death. In addition, we assessed the efficacy of the specific GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5-[H]benzocycloheptene-5-ol-6-ylideneacetic acid) using i.p. administration. All interventions led to significant lifespan extension (22-61%), with NCS-382 being most effective (50-61% survival). To explore the limited human clinical efficacy of VGB, we measured brain GHB and gamma-aminobutyric acid (GABA) levels in SSADH-deficient mice receiving VGB. Whereas high-dose VGB led to the expected elevation of brain GABA, we found no parallel decrease in GHB levels. Our data indicate that, at a minimum, GHB and GABA(B) receptors are involved in the pathophysiology of SSADH deficiency. We conclude that taurine and NCS-382 may have therapeutic relevance in human SSADH deficiency and that the poor clinical efficacy of VGB in this disease may relate to an inability to decrease brain GHB concentrations.

  17. The inkjet cleaner "Hurricane"--another GhB recipe.

    PubMed

    Yambo, C M; McFee, R B; Caraccio, T R; McGuigan, M

    2004-12-01

    Gamma hydroxybutyrate (GHB) is widey used as a sexual enhancement drug, a euphoriant, muscle building agent, a sleep aid, a weight loss agent, and as a date rapeagent. Precursor ingredients such as gammabutyrolactone (GBL) and GHB recipes are available, especially via the Internet. This is a report of an organic inkjet cleaner containing a GHB precursor 1,4-butanediol and butylenegycol. A 26-y-o male fell unconscious during work being unresponsive, with constricted pupils, and convulsing, he did not respond to naloxone. A bottle labeled "Hurricane" was found in his pocket. Five h later the patient awoke and was subsequently discharged with all vitals normal. The patient had recently purchased "Hurricane" as a sleep aid and to treat his panic attacks. It is an organic product with active ingredients similar to ink jet cleaner, the key ingredient being 1,4butanediol, which is metabolized to GHB. In spite of legislative changes restricting GHB, the precursors remain available and continue a public health threat.

  18. gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness.

    PubMed

    Pardi, Daniel; Black, Jed

    2006-01-01

    gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.

  19. [EEG changes during sedation with gamma-hydroxybutyric acid].

    PubMed

    Entholzner, E; Mielke, L; Pichlmeier, R; Weber, F; Schneck, H

    1995-05-01

    Gamma-hydroxybutyric acid (GHB) is a naturally occurring transmitter in the mammalian brain, related to sleep regulation and possibly to energy balance in diving or hibernating animals. It has been used for almost 35 years as an intravenous agent for induction of anaesthesia and for long-term sedation. Its convincing pharmacological properties, without serious adverse effects on circulation or respiration, are compromised by its unpredictable duration of action. This is not a major problem with long-term sedation during ICU treatment. GHB has been used with good results for sedation of patients with severe brain injury, where it compares favourably with barbiturates. In animal studies, it seems to possess a protective action against hypoxia on a cellular and whole organ level. However, in some experimental animals GHB has been shown to produce seizure-like activities, and the compound is being used to produce absence-like seizures. GHB has been used in our ICU for years to provide adequate sedation for patients under controlled ventilation or for patients fighting the respirator during spontaneous respiration. No serious side effects were observed in these patients, while in some patients under haemodialysis hypernatraemia and metabolic alkalosis developed; both were reversible after discontinuation of GHB and restriction of additional sodium input (Somsanit, the commercially available GHB preparation in Germany, contains 9.2 mmol sodium/g; the daily dose averages 20-40 g GHB, i.e. 180-370 mmol sodium). PATIENTS AND METHODS. In 31 patients after major abdominal surgery, sedation was established with GHB 50 mg/kg BW injected via perfusion pump over a 20-min period. No centrally acting medication had been given for at least 2 h. A computer-based multichannel EEG system (CATEEM, MediSyst, Linden) was used, allowing for fast Fourier transformation, spectral analysis and topographical brain mapping. EEG during induction of sedation was followed after a baseline EEG (10

  20. Baclofen as relapse prevention in the treatment of gamma-hydroxybutyrate dependence: a case series.

    PubMed

    Kamal, Rama M; Loonen, Anton J M; Dijkstra, Boukje A G; De Jong, Cornelis A J

    2015-06-01

    In the last decade, gamma-hydroxybutyrate (GHB) abuse and dependence have increased. It has been reported that GHB dependence has a high rate of relapse, serious complications of intoxication, and a potentially life-threatening withdrawal syndrome. Nevertheless, in clinical practice, there is no known medical treatment to support GHB relapse prevention. We describe a case series of patients who were supported through an off-label treatment with baclofen to avoid a relapse into GHB abuse, for a period of 12 weeks. Nine of 11 patients did not relapse while taking a dose ranging from 30 to 60 mg per day, one patient relapsed after 5 weeks, and one stopped after 7 weeks. Baclofen was well tolerated; patients reported mild side effects such as fatigue, nausea, dry mouth, excessive sweating, and depressive feelings. Although systematic evidence is still lacking, our practice-based experience suggests that treatment with baclofen to assist abstinence might be effective in patients with GHB dependence. Further systematic controlled studies are necessary to establish the exact efficacy and safety of baclofen as relapse prevention for GHB-dependent patients.

  1. Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of illicit drugs, and medical examiner cases.

    PubMed

    Jones, A Wayne; Holmgren, Anita; Kugelberg, Fredrik C

    2007-01-01

    Gamma-hydroxybutyrate (GHB) was determined in blood samples from impaired drivers, people arrested for petty drug offenses (non-traffic cases), and GHB-related deaths. The method of analysis involved conversion of GHB into gamma-butyrolactone and determination of the latter by gas chromatography with a flame ionization detector, and with gamma-valerolactone as the internal standard. The mean and median concentrations of GHB in blood from impaired drivers (N=473) were 90 and 84 mg/L, respectively, and offenders were predominantly men (96%) with an average age of 26 year (range 15-50 year). In 185 cases, GHB was the only drug present in blood at mean and median concentrations of 92 and 86 mg/L, respectively. People arrested for petty drug offenses (N=1061) had slightly higher GHB concentrations in their blood: median 118 mg/L for men and 111 mg/L for women. In GHB-related deaths (N=33), the mean and median concentrations were considerably higher: 307 mg/L and 190 mg/L, respectively, and the highest was 2200 mg/L. The typical signs of drug influence noted by the arresting police officers included sedation, agitation, slurred speech, irrational behaviour, jerky movements, and spitting. The short elimination half-life of GHB means that the concentrations in blood decrease rapidly and are probably a lot lower than at the time of driving, which was 30-90 min earlier.

  2. Trans-gamma-hydroxycrotonic acid binding sites in brain: evidence for a subpopulation of gamma-hydroxybutyrate sites.

    PubMed

    Hechler, V; Schmitt, M; Bourguignon, J J; Maitre, M

    1990-03-02

    Trans-gamma-hydroxycrotonate (THCA), a compound naturally present in rat brain, possesses high-affinity binding sites with a heterogeneous distribution which are superimposable with those for gamma-hydroxybutyrate (GHB). Binding studies of THCA on rat brain membranes revealed two binding components, one of high affinity (Kd1, 7 nM, Bmax1 42 fmol/mg protein) and the other of low affinity (Kd2, 2 microM, Bmax2 13 pmol/mg protein). Displacement curves of [3H]THCA by THCA and GHB or of [3H]GHB by THCA are in favour of the existence of a specific high affinity site for THCA. Quantitative autoradiography with image analysis of [3H]THCA binding in rat brain slices indicated that [3H]THCA high affinity binding was displaced at a lower potency by GHB. THCA showed also some selectivity in displacing [3H]GHB from its high affinity binding site (Kd = 95 nM). This mutual overlap favours a subpopulation of GHB receptors, which have THCA as a natural ligand, showing partial agonistic properties compared to GHB. The functional significance of this result remains unknown.

  3. GHB: Forensic examination of a dangerous recreational drug by FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Kindig, J. P.; Ellis, L. E.; Brueggemeyer, T. W.; Satzger, R. D.

    1998-06-01

    Gamma-hydroxybutyric acid (GHB) is an illegal drug that has been abused for its intoxicating effects. However, GHB can also produce harmful physiological effects ranging from mild (nausea, drowsiness) to severe (coma, death). Because GHB is often produced by clandestine manufacture, its concentration, purity, and final form can be variable. Therefore, the analysis of suspected GHB samples using FTIR spectroscopy requires a variety of sample preparations and accessories, based on the sample matrix.

  4. [Hypernatremia caused by treatment with GHB obtained via a doctor's prescription].

    PubMed

    Rood, I M; Seijger, C G W; van Waarde, J A; de Maat, M M R; Verhave, J C; Blans, M J

    2017-01-01

    In the last few years, gamma hydroxybutyric acid (GHB) has been used increasingly as a party drug; this has led to a marked increase in the number of requests for professional help with the treatment of GHB addiction. Pharmaceutical GHB (sodium oxybate, the sodium-salt of GHB), registered for cataplexia in narcolepsy patients, is used off-label to treat the withdrawal symptoms associated with GHB addiction. Pharmaceutical GHB has a high sodium load. In this report we present the cases of two patients who developed symptomatic hypernatremia following treatment with pharmaceutical GHB and who thereafter needed intensive care for the severe withdrawal symptoms that they experienced.

  5. Chemical composition and structure of the microcrystals formed between silver(I) and gamma-hydroxybutyric acid and gamma-hydroxyvaleric acid.

    PubMed

    Bell, Suzanne C; Oldfield, Lucy S; Shakleya, Diaa M; Petersen, Jeffrey L; Mercer, Jennifer W

    2006-07-01

    This study examined microcrystals formed by silver with gamma-hydroxybutyric acid (GHB) and gamma-hydroxyvaleric acid (GHV), the five-carbon analog of GHB, in the presence of silver, copper, and lanthanide nitrates. Distinct microcrystals formed with silver (+1) and lanthanum (+3) ions but not with the copper (+2) ions. The crystals formed with GHB were distinctly different than those formed with GHV and in all cases, the drug microcrystals were easily distinguishable from reagent crystals. X-ray diffraction analysis provided definitive structure for the microcrystals. The morphological differences between the silver-GHB and silver-GHV crystals were characterized using simple measurements such as size and angles provided by image recognition software. The utility of the test for casework was demonstrated using spiked beverage samples.

  6. A fast and reliable method for GHB quantitation in whole blood by GC-MS/MS (TQD) for forensic purposes.

    PubMed

    Castro, André L; Tarelho, Sónia; Dias, Mário; Reis, Flávio; Teixeira, Helena M

    2016-02-05

    Gamma-hydroxybutyric acid (GHB) is an endogenous compound with a story of clinical use since the 1960s. However, due to its secondary effects, it has become a controlled substance, entering the illicit market. A fully validated, sensitive and reproducible method for the quantification of GHB by methanolic precipitation and GC-MS/MS (TQD) in whole blood is presented. Using 100μL of whole blood, obtained results included a LOD and LLOQ of 0.1mg/L and a recovery of 86% in a working range between 0.1 and 100mg/L. This method is sensitive and specific to detect the presence of GHB in small amounts of whole blood (both ante-mortem or post-mortem), and is, to the authors' knowledge, the first GC-MS-MS TQD method that uses different precursor ions and product ions for the identification of GHB and GHB-D6 (internal standard). Hence, this method may be especially useful for the study of endogenous values in this biological sample.

  7. Abuse and therapeutic potential of gamma-hydroxybutyric acid.

    PubMed

    Galloway, G P; Frederick-Osborne, S L; Seymour, R; Contini, S E; Smith, D E

    2000-04-01

    Gamma-hydroxbutyric acid is a compound found in mammalian brain that is structurally related to the neurotransmitters gamma-aminobutyric acid and glutamic acid. Gamma-hydroxybutyric acid effects dopaminergic systems in the brain and may be a neurotransmitter. Gamma-hydroxybutyric acid was first reported as a drug of abuse in 1990 and continues to be abused by bodybuilders, participants of "rave" dance parties, and polydrug abusers. Physical dependence can develop after prolonged, high-dose use, and overdoses have been widely reported. Its use in sexual assaults as a "date rape" drug and availability on the internet have recently emerged. Gamma-hydroxybutyric acid has established efficacy as an anesthetic agent, and preliminary evidence supports its utility in the treatment of alcohol dependence, opiate dependence, and narcolepsy.

  8. Sensorimotor impairment and elevated levels of dopamine metabolites in the neostriatum occur rapidly after intranigral injection of 6-hydroxydopamine or gamma-hydroxybutyrate in awake rats.

    PubMed

    Altar, C A; O'Neil, S; Marshall, J F

    1984-03-01

    The unilateral injection of 6-hydroxydopamine (8 micrograms) into the ventral tegmental area of awake rats produced a rapidly developing and irreversible sensory neglect to contralateral tactile stimuli. This neglect developed in a caudal to rostral direction on the affected body surface and coincided with significant elevation in the concentrations of dopamine and two of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral neostriatum. The unilateral injection of procaine or gamma-hydroxybutyric acid (GHB) into the substantia nigra of awake animals also produced a contralateral neglect that developed in a caudal to rostral direction, but the behavioral effect of these drugs diminished within 1 hr. Concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum were markedly elevated during continuous infusions of procaine or gamma-hydroxybutyric acid. The extent of sensory neglect and changes in dopamine metabolism in the neostriatum varied according to the amount of gamma-hydroxybutyric acid injected into the nigra and according to the proximity of injections of gamma-hydroxybutyric acid to the pars compacta. The rapid onset of sensory neglect following microinjections of 6-hydroxydopamine, procaine or gamma-hydroxybutyric acid is consistent with the ability of each of these drugs to block the conduction of impulses in mesostriatal neurons and suggests that concomitant increases in levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum resulted from decreases in the release of dopamine coupled with increased synthesis of dopamine. These findings also indicate that the catabolism of dopamine to dihydroxyphenylacetic acid or homovanillic acid may originate intraneuronally, without prior release of dopamine and its recapture by mesostriatal terminals, if the flow of impulses in this pathway has been blocked.

  9. Analysis of GHB and 4-methyl-GHB in postmortem matrices after long-term storage.

    PubMed

    Marinetti, Laureen J; Isenschmid, Daniel S; Hepler, Bradford R; Kanluen, Sawait

    2005-01-01

    Postmortem heart blood, peripheral blood, vitreous humor, urine, and bile specimens from 26 autopsy cases were analyzed for the presence of gamma-hydroxybutyric acid (GHB) and gamma-methyl gamma-hydroxybutyric acid (4-Me-GHB) after long-term freezer storage. Cases were selected for which exogenous GHB, gamma-butyrolactone (GBL), gamma valerolactone (GVL), or 1,4-butanediol use was not suspected. One documented positive GHB case subjected to the same storage conditions was also evaluated for comparison. Specimens did not contain any preservatives or additives except heart blood, which contained sodium fluoride (2% w/v). The results of the analysis for GHB in vitreous humor (n = 26) demonstrated, with one exception, concentrations below the limit of detection for the method (5 mg/L). In the exception case, the value was determined to be 7 mg/L. Documented cases of GHB positive fatalities showed vitreous humor concentrations (n = 6) that exceeded this range by a factor of 12 or more. There was no apparent relationship between storage times and GHB concentrations. The data developed in this study demonstrate a postmortem endogenous range for GHB in vitreous humor that is less than or equal to 7 mg/L. Studies of the stored GHB-positive case demonstrated no significant change in concentration over the time period studied. None of the specimens analyzed in this study contained detectable amounts of 4-Me-GHB. This would support the contention that when 4-Me-GHB is detected, it is most likely due to the exogenous consumption of GVL.

  10. Pharmacokinetics of 1,4-butanediol in rats: bioactivation to gamma-hydroxybutyric acid, interaction with ethanol, and oral bioavailability.

    PubMed

    Fung, Ho-Leung; Tsou, Pei-Suen; Bulitta, Jurgen B; Tran, Doanh C; Page, Nathaniel A; Soda, David; Mi Fung, Sun

    2008-01-01

    1,4-Butanediol (BD), a substance of abuse, is bioactivated to gamma-hydroxybutyrate (GHB), but its fundamental pharmacokinetics (PK) have not been characterized. Because this bioactivation is partly mediated by alcohol dehydrogenase, we hypothesized that there may also be a metabolic interaction between ethanol (ETOH) and BD. We therefore studied, in rats, the plasma PK of GHB, BD and ETOH each at two intravenous (IV) doses, when each substance was given alone, and when GHB or BD was co-administered with ETOH. Results showed that bioconversion of intravenously administered BD to GHB was complete, and that both GHB and BD exhibited nonlinear PK. Various population PK models were analyzed using NONMEM VI, and the best disposition model was found to include two PK compartments each for BD, an (unmeasured) putative semialdehyde intermediate (ALD), GHB and ETOH, the presence of nonlinear (Michaelis-Menten) elimination for each compound, and several mutual inhibition processes. The most prominent mutual metabolic inhibition was found between ETOH and BD, while that between GHB and ETOH was not significant. In vitro studies using liver homogenates confirmed mutual metabolic inhibitions between GHB and BD. Oral absorption of BD was best described by a first-order process with lag-time and pre-systemic metabolism from BD to ALD. Oral absorption of BD (as BD plus ALD) was rapid and complete. The fraction of the absorbed dose entering the central compartment as BD was 30% for the 1.58 mmol/kg dose and 55% for the 6.34 mmol/kg dose. At 6.34 mmol/kg IV, the onset of loss of righting reflex (LRR) for BD was significantly delayed vs. that produced by GHB (72.0 +/- 9.1 min vs. 6.7 +/- 0.6 min, respectively, p < 0.001), and the total duration of LRR was prolonged for BD vs. GHB (192 +/- 28 min vs. 117 +/- 2 min, respectively, p < 0.05). Relative to IV dosing, oral BD produced similar but more variable LRR effects. These results may provide a quantitative PK framework for the

  11. Clinical applications of sodium oxybate (GHB): from narcolepsy to alcohol withdrawal syndrome.

    PubMed

    Busardò, F P; Kyriakou, C; Napoletano, S; Marinelli, E; Zaami, S

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a short chain fatty acid endogenously produced within the central nervous system (CNS) and acts as a precursor and metabolite of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Although, it is an illegal recreational drug of abuse, its sodium salt (sodium oxybate) has been utilized as a medication for a number of medical conditions. The first aim of this review was to focus on current applications of sodium oxybate for the treatment of narcolepsy, with a particular emphasis on the key symptoms of this disorder: cataplexy and excessive daytime sleepiness (EDS). Secondly, the effectiveness of sodium oxybate therapy for the treatment of alcohol withdrawal syndrome (AWS) and the maintenance of alcohol abstinence has been assessed. Nowadays, sodium oxybate is the first-line treatment for narcolepsy and it is highly effective in meliorating sleep architecture, decreasing EDS and the frequency of cataplexy attacks in narcoleptic patients. Sodium oxybate currently finds also application in the treatment of AWS and the maintenance of alcohol abstinence in alcoholics. Most of the studies evaluating the efficacy of GHB in the treatment of AWS use a dosage of 50 mg/kg divided in three or four administrations per day. Human studies showed that GHB (dose of 50 mg/kg, divided in three administrations per day) is capable to increase the number of abstinent days, reduce alcohol craving and decrease the number of drinks per day. However, there is limited randomized evidence and, thus, GHB cannot be reliably compared to clomethiazole or benzodiazepines. Some randomized data suggest that GHB is better than naltrexone and disulfiram regarding abstinence maintenance and prevention of craving in the medium term i.e. 3-12 months. It is recommended that GHB should be used only under strict medical supervision, since concerns about the abuse/misuse of the drug and the addiction potential have been arisen.

  12. Effect of gamma-hydroxybutyrate on keratinocytes proliferation: A preliminary prospective controlled study in severe burn patients

    PubMed Central

    Rousseau, Anne-Françoise; Bargues, Laurent; Bever, Hervé Le; Vest, Philippe; Cavalier, Etienne; Ledoux, Didier; Piérard, Gérald E.; Damas, Pierre

    2014-01-01

    Background: Hypermetabolism and hyposomatotropism related to severe burns lead to impaired wound healing. Growth hormone (GH) boosts wound healing notably following stimulation of the production of insulin-like growth factor-1 (IGF1), a mitogen factor for keratinocytes. Gamma-hydroxybutyrate (GHB) stimulates endogenous GH secretion. Aim: To assess effects of GHB sedation on keratinocytes proliferation (based on immunohistochemical techniques). Design: Monocentric, prospective, controlled trial. Materials and Methods: Patients (aging 18-65 years, burn surface area >30%, expected to be sedated for at least one month) were alternately allocated, at the 5th day following injury, in three groups according to the intravenous GHB dose administered for 21 days: Evening bolus of 50 mg/kg (Group B), continuous infusion at the rate of 10 mg/kg/h (Group C), or absence of GHB (Group P). They all received local standard cares. Immunohistochemistry (Ki67/MIB-1, Ulex europaeus agglutinin-1 and Mac 387 antibodies) was performed at D21 on adjacent unburned skin sample for assessing any keratinocyte activation. Serum IGF1 levels were measured at initiation and completion of the protocol. Statistical Analysis: Categorical variables were compared with Chi-square test. Comparisons of medians were made using Kruskal-Wallis test. Post hoc analyses were performed using Mann-Whitney test with Bonferroni correction for multiple comparisons. A P < 0.05 was considered to be statistically significant. Results: A total of 14 patients completed the study (Group B: n = 5, Group C: n = 5, Group P: n = 4). Continuous administration of GHB was associated with a significant higher Ki67 immunolabeling at D21 (P = 0.049) and with a significant higher increase in the IGF1 concentrations at D21 (P = 0.024). No adverse effects were disclosed. Conclusions: Our preliminary data support a positive effect of GHB on keratinocyte proliferation and are encouraging enough to warrant large prospective studies. PMID

  13. Relationship between gamma-hydroxybutyrate plasma concentrations and its electroencephalographic effects in the rat.

    PubMed

    Van Sassenbroeck, D K; De Paepe, P; Belpaire, F M; Rosseel, M T; Martens, P; Boon, P A; Buylaert, W A

    2001-12-01

    In view of the potential interest in an objective parameter for the depth of coma in intoxications with the recreational drug gamma-hydroxybutyrate (GHB), we have studied the relationship between the plasma concentrations and the electroencephalographic (EEG) changes induced by GHB in the rat. Fifteen rats randomly received either 150 (n = 3), 200 (n = 6) or 300 mg kg(-1) (n = 6) GHB over 5 min, followed by a supramaximal dose of 450 mg kg(-1) over 5 min at the end of the experiment. Plasma concentrations were determined with HPLC. The EEG was continuously recorded and the amplitude in the 15.5-30 Hz frequency band was quantified using aperiodic analysis. The plasma concentration-time profiles were fitted to a two-compartment model with Michaelis-Menten elimination. The pharmacokinetic parameters Vmax, Km and the apparent volume of distribution (Vd) proved to be independent of the dose and the mean pooled values were Vmax 2068 +/- 140 microg min(-1) kg(-1), Km 58 +/- 16 microg mL(-1) and Vd 476 +/- 12 mL kg(-1). The EEG amplitude in the 15.5-30 Hz frequency band displayed a monophasic inhibition and the effect-plasma concentration curve showed hysteresis. This hysteresis between EEG effect and plasma concentrations was minimized by simultaneous calculation of hypothetical effect-site concentrations and fitting the effect vs effect-site concentration curve to a sigmoid inhibitory Emax model. The descriptors of this Emax model (Emax, EC50, k(e,0), gamma and E0) were independent of the dose with an equilibration half-life t1/2k(e,0) of 5.6 +/- 0.3 min (mean value of the pooled results of the 5-min treatment groups). To investigate the origin of this hysteresis, a dose of 600 mg kg(-1) GHB was infused over either 45 or 60 min each in three animals. The hysteresis was much less pronounced with 45 min than with 5 min and was absent with 60-min infusions. This indicated that the hysteresis was due to a distribution delay between the central compartment and the effect site

  14. Catabolism of GABA, succinic semialdehyde or gamma-hydroxybutyrate through the GABA shunt impair mitochondrial substrate-level phosphorylation.

    PubMed

    Ravasz, Dora; Kacso, Gergely; Fodor, Viktoria; Horvath, Kata; Adam-Vizi, Vera; Chinopoulos, Christos

    2017-03-11

    GABA is catabolized in the mitochondrial matrix through the GABA shunt, encompassing transamination to succinic semialdehyde followed by oxidation to succinate by the concerted actions of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), respectively. Gamma-hydroxybutyrate (GHB) is a neurotransmitter and a psychoactive drug that could enter the citric acid cycle through transhydrogenation with α-ketoglutarate to succinic semialdehyde and d-hydroxyglutarate, a reaction catalyzed by hydroxyacid-oxoacid transhydrogenase (HOT). Here, we tested the hypothesis that the elevation in matrix succinate concentration caused by exogenous addition of GABA, succinic semialdehyde or GHB shifts the equilibrium of the reversible reaction catalyzed by succinate-CoA ligase towards ATP (or GTP) hydrolysis, effectively negating substrate-level phosphorylation (SLP). Mitochondrial SLP was addressed by interrogating the directionality of the adenine nucleotide translocase during anoxia in isolated mouse brain and liver mitochondria. GABA eliminated SLP, and this was rescued by the GABA-T inhibitors vigabatrin and aminooxyacetic acid. Succinic semialdehyde was an extremely efficient substrate energizing mitochondria during normoxia but mimicked GABA in abolishing SLP in anoxia, in a manner refractory to vigabatrin and aminooxyacetic acid. GHB could moderately energize liver but not brain mitochondria consistent with the scarcity of HOT expression in the latter. In line with these results, GHB abolished SLP in liver but not brain mitochondria during anoxia and this was unaffected by either vigabatrin or aminooxyacetic acid. It is concluded that when mitochondria catabolize GABA or succinic semialdehyde or GHB through the GABA shunt, their ability to perform SLP is impaired.

  15. A pharmacokinetic evaluation and metabolite identification of the GHB receptor antagonist NCS-382 in mouse informs novel therapeutic strategies for the treatment of GHB intoxication.

    PubMed

    Ainslie, Garrett R; Gibson, K Michael; Vogel, Kara R

    2016-12-01

    Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor antagonist, has shown significant efficacy in a murine model of succinic semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder featuring chronic elevation of GHB that blocks the final step of GABA degradation. NCS-382 exposures and elimination pathways remain unknown; therefore, the goal of the present work was to obtain in vivo pharmacokinetic data in a murine model and to identify the NCS-382 metabolites formed by mouse and human. NCS-382 single-dose mouse pharmacokinetics were established following an intraperitoneal injection (100, 300, and 500 mg/kg body weight) and metabolite identification was conducted using HPLC-MS/MS. Kinetic enzyme assays employed mouse and human liver microsomes. Upon gaining an understanding of the NCS-382 clearance mechanisms, a chemical inhibitor was used to increase NCS-382 brain exposure in a pharmacokinetic/pharmacodynamic study. Two major metabolic pathways of NCS-382 were identified as dehydrogenation and glucuronidation. The Km for the dehydrogenation pathway was determined in mouse (Km = 29.5 ± 10.0 μmol/L) and human (Km = 12.7 ± 4.8 μmol/L) liver microsomes. Comparable parameters for glucuronidation were >100 μmol/L in both species. Inhibition of NCS-382 glucuronidation, in vivo, by diclofenac resulted in increased NCS-382 brain concentrations and protective effects in gamma-butyrolactone-treated mice. These initial evaluations of NCS-382 pharmacokinetics and metabolism inform the development of NCS-382 as a potential therapy for conditions of GHB elevation (including acute intoxication & SSADHD).

  16. Endogenous concentrations of GHB in postmortem blood from deaths unrelated to GHB use.

    PubMed

    Korb, Ann-Sophie; Cooper, Gail

    2014-10-01

    Gamma-hydroxybutyrate (GHB) is an endogenous compound, but its presence in postmortem blood presents a challenge when interpreting elevated levels as GHB is misused as a recreational drug and is also produced postmortem. A total of 387 postmortem cases (273 male and 114 female) submitted to the toxicology laboratory between 2010 and 2012 specifically requested the analysis of the ketoacidosis biomarker, beta-hydroxybutyrate (BHB). No reference to GHB use was identified in any of the case files; however, BHB and GHB are measured simultaneously using deuterated GHB as the internal standard (GHB-d6) within a calibration range of 5-500 mg/L. GHB was not detected or <10 mg/L in 18% of the cases (n = 68), between 10 and 50 mg/L in 73% of the cases (n = 283) and between 51 and 193 mg/L in 9% of the cases (n = 36). The manner of death was classified as accidental (n = 11), alcohol-related (n = 237), drug-related (n = 23), homicide (n = 1), natural (n = 91), suicide (n = 9), medical-related (n = 1) and undetermined (n = 14). Six cases had GHB concentrations in excess of 100 mg/L with advanced decomposition changes noted in five of these cases. Moderate-to-advanced decomposition was also noted in 50% (n = 15) of the cases with GHB concentrations in excess of 50 mg/L but <100 mg/L. Approximately one-third of the blood samples tested contained a preservative and although a higher proportion of these samples had GHB concentrations <10 mg/L or not detected (∼30% preserved versus 11% unpreserved), there were still cases with GHB concentrations >51 mg/L (∼6% preserved versus 11% unpreserved). This study highlights the danger of only using a cutoff to establish endogenous levels compared with exogenous use of GHB in postmortem blood.

  17. GHB and Ethanol Effects and Interactions in Humans

    PubMed Central

    Thai, Dung; Dyer, Jo Ellen; Benowitz, Neal L.; Haller, Christine A.

    2008-01-01

    Background Gamma-hydroxybutyrate (GHB) is a common drug of abuse that can produce serious toxicity, particularly when used with other sedatives. We examined the individual and combined effects of GHB and ethanol in human volunteers. Methods Sixteen healthy adults (7 men) were given 50 mg/kg GHB (Xyrem), 0.6 g/kg ethanol in 2 doses, alone and combined in a double-blind, placebo-controlled, crossover study. Plasma concentrations, heart rate (HR), blood pressure (BP), and oxygen saturation (O2sat) were serially monitored for 24 hours. Results Adverse events included 2 instances of hypotension and 6 episodes of vomiting with GHB-plus-ethanol ingestion. Oxygen saturation was decreased by GHB and ethanol individually, and maximally decreased by the drugs combined (max −2.1% ± 0.3%, P < 0.0001 vs placebo). Compared with baseline, systolic and diastolic BP were significantly decreased, and HR was increased by ethanol but not affected by GHB alone (maximum systolic BP change −15.7 ± 3.0 mm Hg, P = 0.0006; maximum HR change 13.5 ± 2.3 beats per minute, P = 0.006). Ethanol coingestion resulted in 16% higher GHB maximal plasma concentration and 29% longer elimination half-life, indicating possible enhanced bioavailability or reduced clearance of GHB caused by ethanol, however, these effects were not statistically significant. Conclusions Modest doses of GHB do not affect hemodynamic function, but O2sat was decreased. Gamma-hydroxybutyrate-plus-ethanol resulted in more adverse effects, including gastrointestinal disturbances, hypotension, and decreased O2sat, but only minimal pharmacokinetic interactions were observed. PMID:16974199

  18. GHB Urine Concentrations After Single-Dose Administration in Humans

    PubMed Central

    Haller, Christine; Thai, Dung; Jacob, Peyton; Dyer, Jo Ellen

    2008-01-01

    Gamma-hydroxybutyric acid (GHB) is used as an illicit drug and is implicated in drug-facilitated sexual assault, but it also has some therapeutic uses. Detection of GHB in urine is important for forensic testing and could be of clinical benefit in overdose management. Urine GHB concentration-time profiles have not been well-characterized or correlated with doses used therapeutically. GHB levels were measured by gas chromatography–mass spectrometry in urine collected over 24 h from 16 adults administered single doses of 50 mg/kg GHB (Xyrem®) alone and combined with 0.6 g/kg ethanol. Peak GHB urine concentrations averaged 150–200 mg/L and occurred in the 0–3 h urine collection. Significant variability in GHB urine levels between individuals was observed. Caucasians had lower urine concentrations than other races/ethnicities (p = 0.03). Men had lower GHB levels than women in the first 3 h after dosing (p = 0.038). Coingestion of ethanol did not significantly affect renal clearance of GHB, but urine GHB concentrations were lower in the first 3 h when ethanol and GHB were coingested (p = 0.039). At a proposed cut-off of 10 mg/L to distinguish endogenous versus exogenous GHB levels, 12.5% of the samples collected from 3 to 6 h, 81.3% of samples collected from 6 to 12 h, and 100% of urine specimens collected from 12 to 24 h were below this level. We conclude that the detection time for GHB in urine may be shorter than the previously reported 12-h window in some people taking therapeutic doses of GHB. PMID:16872565

  19. A multi-drug intoxication fatality involving Xyrem (GHB).

    PubMed

    Akins, Brianne E; Miranda, Estuardo; Lacy, J Matthew; Logan, Barry K

    2009-03-01

    Gamma-hydroxybutyrate (GHB) is best known as a recreational depressant drug, whose use has also been implicated in drug facilitated sexual assault cases. It is also available as a therapeutic agent (Xyrem) used for the treatment of daytime sleepiness or cataplexy associated with narcolepsy. This is a report of a case of a 53-year-old woman undergoing treatment with Xyrem for narcolepsy. The decedent was also prescribed tramadol, gabapentin, cetirizine, modafinil, carisoprodol, and Xyrem. Toxicological analysis of the blood revealed GHB 165.6 mg/L, and 90.7 mg/L in the urine. Blood GHB concentrations in the range 156-260 mg/L have been reported to induce moderately sound sleep. The combined use of central nervous system depressant drugs, together with her problematic sleep apnea, and snoring (both contraindications for GHB use) were determined to have caused this subject's death. The manner of death was determined to be accidental.

  20. GHB acid: A rage or reprive.

    PubMed

    Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita

    2013-10-01

    Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties) who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs.

  1. GHB acid: A rage or reprive

    PubMed Central

    Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita

    2013-01-01

    Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties) who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs. PMID:24350046

  2. Detection of gamma-hydroxybutyrate in hair: validation of GC-MS and LC-MS/MS methods and application to a real case.

    PubMed

    Bertol, Elisabetta; Argo, Antonina; Procaccianti, Paolo; Vaiano, Fabio; Di Milia, Maria Grazia; Furlanetto, Sandra; Mari, Francesco

    2012-11-01

    A gas chromatography-mass spectrometry (GC-MS) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method were validated for quantifying endogenous and exogenous hair concentrations of gamma-hydroxybutyrate (GHB). The GC-MS method is based on overnight extraction of 25 mg hair in NaOH at 56 °C, liquid/liquid extraction in ethylacetate and trimethylsylil derivatization; analysis is by electron ionization and single ion monitoring of three ions. The LC-MS/MS method entails a rapid digestion of 25 mg hair with NaOH at 75 °C for 40 min, liquid/liquid extraction in ethylacetate and reconstitution of the extract in the LC mobile phase; negative ion electrospray ionization and multiple reaction monitoring (MRM) analysis are employed for the LC-MS/MS detection. In both cases, GHB-d6 is used as an internal standard. The endogenous amount in "blank" hair are estimated by the standard addition method. Limits of detection are 0.4 and 0.5 ng/mg for GC-MS and LC-MS/MS respectively, while the limit of quantification (LOQ) is 0.6 ng/mg for both methods; the GC-MS method proved to be linear in the range 1-50 ng/mg whereas linearity was demonstrated from 0.6 to 50 ng/mg for the LC-MS/MS; imprecision and inaccuracy were always lower than 23% for quality controls samples. The two methods were applied to a real case of a man addicted to GHB; the drug concentration in segments from 17 cm hair strand well correlated with self-reported use of GHB in different periods of his life. Performances of the two methods were similar.

  3. Increases in Serum Growth Hormone Concentrations Associated with GHB Administration.

    PubMed

    Brailsford, Alan D; Bartlett, Christiaan; Kicman, Andrew T; Cowan, David A

    2017-01-01

    The administration of gamma-hydroxybutyrate (GHB) has been reported to augment the increase in growth hormone (GH) secretion associated with the onset of sleep. The ability of GHB to stimulate GH production in the absence of sleep in both male and female volunteers was investigated as part of a GHB administration study. Twelve healthy volunteers (six men and six women) were given a small oral dose (25 mg/kg) of GHB (as Xyrem(®)) at 10:00 h. Basal blood samples (as serum) were taken 10 min prior to GHB administration, with additional samples taken at 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 240, 360 and 480 min post-administration. The serum concentrations of GHB were measured by GC-MS and GH by immunometric assay. Following GHB administration, volunteers exhibited effects consistent with mild sedation, i.e., relaxed with normal responses to verbal stimuli. Despite none being asleep, an increase in serum GH concentration occurred in 11 out of the 12 volunteers (5 women and 6 men). In these volunteers, peak GH concentrations occurred 45-60 min post-administration compared with a mean serum tmax for GHB of 23 min (SD = 5.4 min). The absolute increase in GH was similar for men and women, averaging 3.4 and 3.7 ng/mL, respectively. The mean intra-individual increase in GH was much greater in males (29 times) compared with females (2 times), as males had (as expected) smaller basal GH concentrations (mean = 0.26 ng/mL) compared with females (mean = 5.4 ng/mL). After maximizing, the GH concentration decreased rapidly (in agreement with GHB concentrations), returning to basal concentrations at ~90-120 min post-administration. GHB administration at a small therapeutic dose results in increases in serum GH concentrations in healthy male and female volunteers in the absence of sleep onset.

  4. What constitutes a normal ante-mortem urine GHB concentration?

    PubMed

    Mari, Francesco; Politi, Lucia; Trignano, Claudia; Di Milia, Maria Grazia; Di Padua, Marianna; Bertol, Elisabetta

    2009-04-01

    Gamma-hydroxybutyric acid (GHB) is endogenously produced within the central nervous system, however it is also used as a medication for the treatment of a variety of clinical conditions, sold under the name Zyrem in the United States and Alcover in Europe. It is a very dangerous drug with a very limited safety margin, and is classified as a controlled substance in many countries. The interpretation of post-mortem studies of GHB concentrations is problematic; GHB can be detected in urine and blood from non-GHB users, both before and after death, and concentrations in both matrices may rise with prolonged storage. Because it is produced as a post-mortem artifact, forensically defensible cut-offs for post-mortem blood concentrations have yet to be established. Given the enormous degree of inter and intra-individual variation in GHB production that has been documented, it is unlikely they ever will. The important issue for forensic scientists is whether the detection of GHB in urine, in concentrations above some yet to be determined value, can be used as evidence for drug facilitated assault. In an attempt to see if a cut-off level could be determined we analyzed urine from 39 alcoholics who were being treated with known oral doses of Alcover (group 1), and compared the results with concentrations found in the urine of 30 volunteers who had no exogenous GHB intake (group 2), and 30 urine specimens taken from the alcoholics before they initiated GHB therapy (Alcover treatment group 3). More than one third (36.6%) of subjects being treated with GHB were found to have urinary GHB concentration that fell between 2.75 and 10 microg/mL. The data suggests that caution must be used when applying the currently used cut-off of 10 microg/mL.

  5. GC-MS Analysis of [gamma]-Hydroxybutyric Acid Analogs: A Forensic Chemistry Experiment

    ERIC Educational Resources Information Center

    Henck, Colin; Nally, Luke

    2007-01-01

    An upper-division forensic chemistry experiment is described. It involves using glycolic acid and sodium glycolate as analogs of [gamma]-hydroxybutyric acid and its sodium salt. The experiment shows the use of silylation in GC-MS analysis and gives students the opportunity to work with a commonly used silylating reagent,…

  6. 21 CFR 1304.26 - Additional recordkeeping requirements applicable to drug products containing gamma-hydroxybutyric...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Additional recordkeeping requirements applicable to drug products containing gamma-hydroxybutyric acid. 1304.26 Section 1304.26 Food and Drugs DRUG... accordance with an application under section 505 of the Federal Food, Drug, and Cosmetic Act must...

  7. Intoxication of a Young Girl Reveals the Pitfalls of GHB Rapid Screening.

    PubMed

    Franken, Linda G; Andrews, Louise M; Slooff, Valerie D; de Wildt, Saskia N; Koch, Birgit C P

    2016-02-01

    The authors discuss the case of a 14-year-old girl who was transferred to the ICU of our hospital with ethanol intoxication (3.3 g/L), loss of consciousness (E5M3V1), and severe amnesia on recovery that was suspected of gamma-hydroxybutyric acid (GHB) intoxication. STAT toxicology screening may be necessary, when sexual assault under GHB intoxication is suspected. Therefore, the initial analysis of a urine sample was performed with a new enzymatic assay analysis for GHB. The enzymatic assay reported a GHB concentration of 26 mg/L, which is above the cut-off value of 10 mg/L. This cut-off value is to differentiate endogenous and exogenous levels because low levels of GHB occur naturally in the body. However, confirmation of these results by gas chromatography, which is common practice to confirm a positive GHB, gave a negative result. This discrepancy is probably contributed to interference of ethanol with the assay. This is a substantial downside of the GHB rapid screening, since the combination of GHB and ethanol is common. It is therefore advised to confirm that the positive GHB results are lower than 50 mg/L by gas chromatography, when using the rapid screening. This way the false-positive results and consequent inappropriate social and legal actions may be avoided.

  8. Comparative abuse liability of GHB and ethanol in humans.

    PubMed

    Johnson, Matthew W; Griffiths, Roland R

    2013-04-01

    Gamma-hydroxybutyric acid (GHB; sodium oxybate) is approved for narcolepsy symptom treatment, and it is also abused. This study compared the participant-rated, observer-rated effects, motor/cognitive, physiological, and reinforcing effects of GHB and ethanol in participants with histories of sedative (including alcohol) abuse. Fourteen participants lived on a residential unit for ∼1 month. Sessions were conducted Monday through Friday. Measures were taken before and repeatedly up to 24 hours after drug administration. Participants were administered GHB (1, 2, 4, 6, 8, and 10 g/70 kg), ethanol (12, 24, 48, 72, 96, and 120 g/70 kg), or placebo in a double-blind, within-subjects design. For safety, GHB and ethanol were administered in an ascending dose sequence, with placebos and both drugs intermixed across sessions. The sequence for each drug was stopped if significant impairment or intolerable effects occurred. Only 9 and 10 participants received the full dose range for GHB and ethanol, respectively. The highest doses of GHB and ethanol showed onset within 30 minutes, with peak effects at 60 minutes. GHB effects dissipated between 4 and 6 hours, whereas ethanol effects dissipated between 6 and 8 hours. Dose-related effects were observed for both drugs on a variety of measures assessing sedative drug effects, abuse liability, performance impairment, and physiological effects. Within-session measures of abuse liability were similar between the two drugs. However, postsession measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, most likely as a result of the delayed aversive ethanol effects (e.g., headache).

  9. Comparative abuse liability of GHB and ethanol in humans

    PubMed Central

    Johnson, Matthew W.; Griffiths, Roland R.

    2013-01-01

    Gamma-hydroxybutyric acid (GHB; sodium oxybate) is approved for narcolepsy symptom treatment, and it is also abused. This study compared the participant-rated, observer-rated effects, motor/cognitive, physiological, and reinforcing effects of GHB and ethanol in participants with histories of sedative (including alcohol) abuse. Fourteen participants lived on a residential unit for ~1 month. Sessions were conducted Monday through Friday. Measures were taken before, and repeatedly up to 24 hours after drug administration. Participants were administered GHB (1, 2, 4, 6, 8, and 10 g/70kg), ethanol (12, 24, 48, 72, 96, and 120 g/70kg), or placebo in a double-blind, within-subjects design. For safety, GHB and ethanol were administered in an ascending dose sequence, with placebos and both drugs intermixed across sessions. The sequence for each drug was stopped if significant impairment or intolerable effects occurred. Only 9 and 10 participants received the full dose range for GHB and ethanol, respectively. The highest doses of GHB and ethanol showed onset within 30 minutes, with peak effects at 60 minutes. GHB effects dissipated between 4 and 6 hours, while ethanol effects dissipated between 6 and 8 hours. Dose-related effects were observed for both drugs on a variety of measures assessing sedative drug effects, abuse liability, performance impairment, and physiological effects. Within-session measures of abuse liability were similar between the two drugs. However, post-session measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, due most likely to the delayed aversive ethanol effects (e.g., headache). PMID:23421353

  10. γ-Hydroxybutyrate and the GABAergic footprint: a metabolomic approach to unpicking the actions of GHB.

    PubMed

    Nasrallah, Fatima A; Maher, Anthony D; Hanrahan, Jane R; Balcar, Vladimir J; Rae, Caroline D

    2010-10-01

    Gamma-hydroxybutyrate is found both naturally in the brain and self-administered as a drug of abuse. It has been reported to act at endogenous γ-hydroxybutyrate (GHB) receptors and GABA(B) receptors [GABA(B)R], and may also be metabolized to GABA. Here, the metabolic fingerprints of a range of concentrations of GHB were measured in brain cortical tissue slices and compared with those of ligands active at GHB and GABA-R using principal components analysis (PCA) to identify sites of GHB activity. Low concentrations of GHB (1.0 μM) produced fingerprints similar to those of ligands active at GHB receptors and α4-containing GABA(A)R. A total of 10 μM GHB clustered proximate to mainstream GABAergic synapse ligands, such as 1.0 μM baclofen, a GABA(B)R agonist. Higher concentrations of GHB (30 μM) clustered with GABA(C)R agonists and the metabolic responses induced by blockade of the GABA transporter-1 (GAT1). The metabolic responses induced by 60 and 100 μM GHB were mimicked by simultaneous blockade of GAT1 and GAT3, addition of low concentrations of GABA(C)R antagonists, or increasing cytoplasmic GABA concentrations by incubation with the GABA transaminase inhibitor vigabatrin. These data suggest that at concentrations > 30 μM, GHB may be active via metabolism to GABA, which is then acting upon an unidentified GABAergic master switch receptor (possibly a high-affinity extrasynaptic receptor), or GHB may itself be acting directly on an extrasynaptic GABA-R, capable of turning off large numbers of cells. These results offer an explanation for the steep dose-response curve of GHB seen in vivo, and suggest potential target receptors for further investigation.

  11. Detection of exogenous GHB in blood by gas chromatography-combustion-isotope ratio mass spectrometry: implications in postmortem toxicology.

    PubMed

    Saudan, Christophe; Augsburger, Marc; Kintz, Pascal; Saugy, Martial; Mangin, Patrice

    2005-01-01

    Because GHB (gamma-hydroxybutyrate) is present in both blood and urine of the general population, toxicologists must be able to discriminate between endogenous levels and a concentration resulting from exposure. In this paper, we propose a procedure for the detection of exogenous GHB in blood by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Following liquid-liquid and solid-phase extractions, GHB is derivatized to GHB di-TMS before analysis by GC-C-IRMS. Significant differences in the carbon isotopic ratio (delta(13)C-values > 13.5 per thousand) were found between endogenous and synthetic GHB. Indeed, for postmortem blood samples with different GHB concentrations (range: 13.8-86.3 mg/L), we have obtained GHB delta(13)C-values ranging from -20.6 to -24.7 per thousand, whereas delta(13)C-values for the GHB from police seizure were in the range -38.2 to -50.2 per thousand. In contrast to the use of cut-off concentrations for positive postmortem blood GHB concentrations, this method should provide an unambiguous indication of the drug origin.

  12. GHB differentially affects morphine actions on motor activity and social behaviours in male mice.

    PubMed

    Maldonado, C; Rodriíuez-Arias, M; Aguilar, M A; Miñarro, J

    2003-09-01

    There are several reports suggesting that gamma-hydroxybutyric acid (GHB) influences the endogenous opioid system. The present study aimed to investigate the effects of GHB on motor and social activities and to examine its influence on morphine's actions on these behaviours. In a first experiment, several doses of GHB were studied but only the highest (200 and 400 mg/kg) produced a decrease in spontaneous motor activity measured in an actimeter cage. When hyperactivity induced by injecting 50 mg/kg of morphine was evaluated, all the GHB doses efficiently counteracted this morphine action. Using the paradigm of isolation-induced aggression, administration of 200 mg/kg of GHB significantly decreased threat and attack without impairing motor activity and, in addition, increased time spent in social contact. GHB increased morphine's suppression of threat or nonsocial exploratory behaviours. In conclusion, the interaction between GHB and the opioid systems was confirmed, with the drug having an additive effect on morphine-affected social behaviours but counteracting morphine-induced increases in motor activity.

  13. An improved method for the analysis of GHB in human hair by liquid chromatography tandem mass spectrometry.

    PubMed

    Jagerdeo, Eshwar; Montgomery, Madeline A; LeBeau, Marc A

    2015-03-01

    The abuse of gamma-hydroxybutyric acid (GHB) and its suspicion in cases of suspected drug-facilitated sexual assault is of keen interest to forensic toxicology laboratories. This paper reports an extraction, separation and detection procedure for GHB in hair utilizing a combination of liquid-liquid extraction and solid-phase extraction using ethyl acetate and Oasis Max(®) cartridge, respectively, after the hair sample was digested. Analysis was by LC-MS-MS using a gradient separation on an Acclaim(®) Trinity(TM) P1 column performing three multiple-reaction monitoring (MRM) transitions each for GHB and its internal standard. The procedure was validated over a range from 0.4 to 50 ng/mg with estimated limit of detection (LOD) of 0.33 and an administratively set limit of quantitation (LOQ) of 1.2 ng/mg. Twenty hair specimens collected from individuals with no known exposure to GHB were analyzed for matrix interferences and to establish initial background levels of GHB. A wide range of endogenous GHB levels were observed in these samples (from less than the LOQ to 4.4 ng/mg). The results suggest the need for additional studies to better establish the full range of endogenous GHB levels in hair and that extreme caution is required in interpreting GHB findings in hair samples.

  14. [The knowledge about gamma-hydroxybutyric acid as by students of Physical Education Academy].

    PubMed

    Chwaluk, Paweł; Chwaluk, Agnieszka; Parnicki, Florian

    2009-01-01

    Gamma-hydroxybutyric acid is a substance stealthily used by criminals to facilitate sexual assaults. It is also known as doping agent in sports. Physical Education Academies should prepare their graduates to be educators for young people, their trainers, organizers of sports and recreational events. Second year students of two majors: physical education and tourism and recreation were surveyed by means of questionnaire on "date-rape drug". As much as 320 among 327 students surveyed had heard about "date-rape drug". However their knowledge on it was shallow and unsystematic. None of the surveyed knew that the substance of "date-rape drug" could also be used as a doping agent. Only 31% of respondents were aware of existence of the test to detect "date-rape drug" in drinks. Physical Education Academy students should be thoroughly and relevantly educated on the matter of pharmacologic doping agents and drugs endangerment.

  15. Addicted to driving under the influence--a GHB/GBL case report.

    PubMed

    Couper, Fiona J; Logan, Barry K

    2004-09-01

    A 38-year-old male was arrested 7 times over an 8-month period for driving under the influence (DUI) of drugs. In each incident, gamma-hydroxybutyrate (GHB) was determined to be the causative agent. A blood specimen was drawn between 1.5 and 2.5 h after first police contact in each arrest. GHB was analyzed by gas chromatography-mass spectrometry, following extraction from blood using ethyl acetate and subsequent derivatization using BSTFA/TMCS. Blood GHB concentrations ranged from 44 to 184 mg/L (N = 7, mean 100 mg/L, median 73 mg/L). Overall signs of impairment included erratic driving (severe lane travel, collisions, and near-collisions), slurred speech, disorientation, slow to react, shaking, agitation, unable to focus, poor coordination and balance, poor performance in field sobriety tests, somnolence, and unconsciousness. On only one occasion were other drugs present in the subject's blood (thiopental and diazepam), which may have contributed to the observed driving impairment. During several police interviews, the subject stated he was addicted to GHB and gamma-butyrolactone (GBL), and admitted to previously taking "RenewTrient", "Dream On", "V35", "fitness supplements", and/or "GBL". During the same period as his DUI arrests, the subject had been admitted at least six times to different hospitals for GHB/GBL intoxications.

  16. Comparison of endogenous GHB concentrations in blood and hair in death cases with emphasis on the post mortem interval.

    PubMed

    Castro, André L; Tarelho, Sónia; Dias, Mário; Reis, Flávio; Teixeira, Helena M

    2016-07-01

    Gamma-hydroxybutyric acid (GHB) is an endogenous compound which has a story of clinical use and illicit abuse since the 1960's. The possibility to use a multi-sample approach for GHB evaluation, including whole blood and hair, to better characterize a forensic toxicology case and evaluate a possible causal association with the death is an exciting up-to-date issue. In addition, its post-mortem behaviour, namely regarding degradation and metabolism, has been increasingly investigated as a putative biomarker for post-mortem interval (PMI) estimation. Thus, in order to contribute to clarification of this specific aspect, whole blood and hair post-mortem GHB levels were evaluated in 32 real cases with previous information on death and autopsy data. The results obtained suggest that the PMI (until 5 days between death and sampling) influences GHB whole blood concentration, but not GHB levels in hair samples. No differences were encountered for the other parameters evaluated, including age, gender, cause of death and presence or absence of substances. This study brings new insights regarding the usefulness of GHB levels in forensic toxicology, which might be further strengthened with larger, but comparable, studies from other laboratories and institutions in the context of legal medicine.

  17. 76 FR 17968 - Manufacturer of Controlled Substances; Notice of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... Enforcement Administration (DEA) to be registered as a bulk manufacturer of Gamma Hydroxybutyric Acid (GHB... Gamma Hydroxybutyric Acid (GHB) ] (2010) in bulk active pharmaceutical ingredient (API) form...

  18. Identification of GHB and morphine in hair in a case of drug-facilitated sexual assault.

    PubMed

    Rossi, Riccardo; Lancia, Massimo; Gambelunghe, Cristiana; Oliva, Antonio; Fucci, Nadia

    2009-04-15

    The authors present the case of a 24-year-old girl who was sexually assaulted after administration of gamma-hydroxybutyrate (GHB) and morphine. She had been living in an international college for foreign students for about 1 year and often complained of a general unhealthy feeling in the morning. At the end of the college period she returned to Italy and received at home some video clips shot by a mobile phone camera. In these videos she was having sex with a boy she met when she was studying abroad. Toxicological analysis of her hair was done: the hair was 20-cm long. A 2/3-cm segmentation of all the length of the hair was performed. Morphine and GHB were detected in hair segments related to the period of time she was abroad. The analyses of hair segments were performed by gas chromatography/mass spectrometry (GC/MS) and the concentration of morphine and GHB were calculated. A higher value of GHB was found in the period associated with the possible criminal activity and was also associated with the presence of morphine in the same period.

  19. Pharmacological Treatment in γ-Hydroxybutyrate (GHB) and γ-Butyrolactone (GBL) Dependence: Detoxification and Relapse Prevention.

    PubMed

    Kamal, Rama M; van Noorden, Martijn S; Wannet, Wim; Beurmanjer, Harmen; Dijkstra, Boukje A G; Schellekens, Arnt

    2017-01-01

    The misuse of γ-hydroxybutyrate (GHB) for recreational purposes has resulted in an increase in GHB-related problems such as intoxications, dependence and withdrawal in several countries in Europe, Australia and the US over the last decade. However, prevalence rates of misuse of GHB and its precursor, γ-butyrolactone (GBL), are still relatively low. In this qualitative review paper, after a short introduction on the pharmacology of GHB/GBL, followed by a summary of the epidemiology of GHB abuse, an overview of GHB dependence syndrome and GHB/GBL withdrawal syndrome is provided. Finally, the existing literature on management of GHB detoxification, both planned and unplanned, as well as the available management of GHB withdrawal syndrome, is summarized. Although no systematic studies on detoxification and management of withdrawal have been performed to date, general recommendations are given on pharmacological treatment and preferred treatment setting.

  20. Quantitative analysis of the endogenous GHB level in the hair of the Chinese population using GC/MS/MS.

    PubMed

    Shi, Yan; Cui, Xiaopei; Shen, Min; Xiang, Ping

    2016-04-01

    Endogenous production complicates interpretation when gamma-hydroxybutyrate (GHB) is measured in hair for forensic purposes. A method capable of quantifying the endogenous concentration of GHB in human head hair was developed and validated using GC/MS/MS. Hair was digested under alkaline conditions (1 mol/L NaOH, 90 °C 10 min), and GHB-d6 was used as an internal standard. Before derivatization with BSTFA and ethyl acetate, a liquid-liquid extraction with ethyl acetate under acidic conditions was performed. GHB-TMS derivatives were detected using GC/MS/MS in the multiple-reaction monitoring mode. This method exhibited good linearity (y = 0.018x + 0.038, R(2) = 0.9998), and the limit of detection was 0.02 ng/mg. The extraction recoveries were more than 60%, and the inter-day and intra-day relative standard deviations (RSD) were less than 15%. This method has been applied for the analysis of the endogenous GHB in hair samples from 66 drug-free Chinese donors. The mean measured concentration for 0-3 cm hair was 1.93 ± 1.40 ng/mg (n = 66), and extreme values were in the range of 0.28-4.91 ng/mg. The mean male endogenous GHB level was 2.95 ng/mg (0.92-4.91 ng/mg, n = 35), while the mean female level was 0.77 ng/mg (0.28-1.95 ng/mg, n = 31). This method was applied to a forensic case for the determination of GHB in hair samples but it is hard to make a reasonable "cut off" in hair. The solution is to use each subject as his own control.

  1. Preliminary Web-Based Measures Development for GHB: Expectancies, Functions, and Withdrawal

    PubMed Central

    Stein, L.A.R.; Lebeau, Rebecca; Clair, Mary; Martin, Rosemarie; Bryant, Monte; Storti, Susan

    2015-01-01

    Background Much of what is understood regarding gamma hydroxybutyrate (GHB) treatment is based on hospital case studies for overdose and withdrawal, and there are currently no measures developed specifically for GHB or its analogs (e.g., gamma butyrolactone and 1,4-butanediol) to assess drug effect expectancies, reasons for starting use, withdrawal effects, and knowledge and opinions about use. Objectives This pilot study (N = 61) was conducted to begin measures development to assess experiences, functions of use, and opinions regarding use as indicated by respondents taking a Web-based survey. Methods Minimum average partial correlation and parallel analysis procedures are employed to create scales. Results Scales were developed to assess expectancies, reasons for use, withdrawal, and knowledge/opinions of use with median α = .79 and that account for 8.69–24.17% of the variance. Conclusion Scales have relatively good psychometric properties and replication is needed. Scientific Significance GHB-specific measures may greatly assist in furthering our understanding of protective and risk factors for use, and withdrawal phenomena. PMID:22175869

  2. A long hangover from party drugs: residual proteomic changes in the hippocampus of rats 8 weeks after γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination.

    PubMed

    van Nieuwenhuijzen, Petra S; Kashem, Mohammed A; Matsumoto, Izuru; Hunt, Glenn E; McGregor, Iain S

    2010-07-01

    3,4-Methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate (GHB) are popular party drugs that are used for their euphoric and prosocial effects, and sometimes in combination. Both drugs increase markers of oxidative stress in the hippocampus and can cause lasting impairments in hippocampal-dependent forms of memory. To gain further information on the biochemical mechanisms underlying these effects, the current study examined residual changes in hippocampal protein expression measured 8 weeks after chronic administration of GHB (500mg/kg), MDMA (5mg/kg) or their combination (GHB/MDMA). The drugs were administered once a day for 10 days in an environment with an elevated ambient temperature of 28 degrees C. Results showed significant changes in protein expression, relative to controls, in all three groups: MDMA and GHB given alone caused residual changes in 8 and 5 proteins respectively, while the GHB/MDMA combination significantly changed 6 proteins. The altered proteins had roles in neuroplasticity, neuroprotection, intracellular signalling and cytoskeletal function. The largest change (-4.3-fold) was seen in the MDMA group with the protein C-crk: a protein implicated in learning-related neuroplasticity. The second largest change (3.0-fold) was seen in the GHB group in Glutathione-S-transferase (GST), a protein that protects against oxidative stress. Two cytoskeletal proteins (Tubulin Folding Cofactor B and Tropomyosin-alpha-3 chain) and one plasticity related protein (Neuronal Pentraxin-1 NP1) were similarly changed in both the MDMA and the GHB groups, while two intracellular signalling proteins (alpha-soluble NSF-attachment protein and subunits of the V-type proton ATPase) were changed in both the MDMA/GHB and the MDMA groups. These results provide some insight into the molecular pathways possibly underlying the lasting cognitive deficits arising from GHB and/or MDMA use.

  3. γ-Hydroxybutyrate: experience of 9 years of γ-hydroxybutyrate (GHB)-related incidents during rave parties in The Netherlands.

    PubMed

    Krul, Jan; Girbes, Armand R J

    2011-04-01

    OBJECTIVE. The objective of this study was to determine the health disturbances and to assess the severity of the incidents as reported during a 9-year experience of gamma-hydroxybutyrate (GHB)-related First Aid Attendees attending First Aid Stations at rave parties. DESIGN. This study was a prospective observational study of self-referred patients from the year 2000 to 2008. During rave parties, First Aid Stations were staffed with specifically trained medical and paramedical personnel. Patients were diagnosed and treated, and data were recorded using standardized methods. RESULTS. During a 9-year period with 202 rave parties, involving approximately three million visitors, 22 604 First Aid Attendees visited the First Aid Stations, of which 771 reported GHB-related health problems. The mean age of the GHB-using First Aid Attendees was 25.7 ± 6.1 years, most of them (66.4%) were male. Approximately one-third (32.7%) of them used one substance, while 48.1% combined GHB with ecstasy, alcohol, or cannabis. One of five (19.2%) combined GHB with other substances or more than one substance. One case was categorized as severe/life-threatening and 202 (26.2%) cases as moderate, requiring further medical care. In total, 43 (5.6%) First Aid Attendees needed hospital care. The most encountered health disturbance was altered consciousness. Combinations of altered consciousness, vomiting, and/or low body temperature were found in 186 cases (24.1%) and considered to be potentially dangerous. GHB-related First Aid Attendees required a longer stay at the First Aid Stations than the total group First Aid Attendees did (median 45 min vs 10 min). CONCLUSION. We found very little, severe short-term GHB-related health disturbances during rave parties in The Netherlands. Hospital referrals were rare. The most found symptom was altered consciousness, sometimes accompanied by vomiting and low body temperature. At events where the visitors use GHB, a well-trained and qualified

  4. The Use of GHB to Facilitate Sexual Assault.

    PubMed

    Marinetti, L; Montgomery, M A

    2010-01-01

    γ-Hydroxybutyric acid (GHB) and its metabolic precursors, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), may be among the most favored drugs used to commit drug-facilitated sexual assault (DFSA). In fact, federal legislation was enacted in the form of the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000 to control and penalize use and distribution of GHB, GBL, and 1,4-BD. Unfortunately, solid proof of their use in many cases is difficult to obtain because GHB, GBL, and 1,4-BD have strong sedative and memory-impairing effects and are rapidly eliminated after ingestion. To further complicate the matter, GHB is a metabolite of γ-aminobutyric acid (GABA), a naturally occurring neurotransmitter in humans. This review focuses on the chemistry and pharmacology of these drugs and their use in DFSA. An overview of analytical techniques used to identify their presence is provided, as well as guidance on the toxicological interpretation of findings of GHB in biological specimens.

  5. 3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone

    SciTech Connect

    Vayer, P.; Gobaille, S.; Mandel, P.; Maitre, M.

    1987-08-03

    An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg el-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP. 34 references, 4 figures.

  6. Determination of GHB in human hair by HPLC-MS/MS: Development and validation of a method and application to a study group and three possible single exposure cases.

    PubMed

    Bertol, Elisabetta; Mari, Francesco; Vaiano, Fabio; Romano, Guido; Zaami, Simona; Baglìo, Giovanni; Busardò, Francesco Paolo

    2015-05-01

    Gamma-hydroxybutyrate (GHB) over the last two decades has generated increased notoriety as a euphoric and disinhibiting drug of abuse in cases of drug-related sexual assault and for this reason it is considered a 'date rape' drug. The first aim of this paper was to develop and fully validate a method for the detection of GHB in human hair by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) after liquid-liquid extraction (LLE). The second aim was the application of the method to hair samples of 30 GHB-free users in order to determine the basal level. The results obtained showed no significant differences in endogenous concentrations (p = 0.556) between hair samples of the three groups (black, blonde, and dyed hair) and the age and sex of the subjects did not affect the endogenous levels. Another 12 healthy volunteers, with no previous history of GHB use, were selected and a single dose (25 mg/Kg) was orally administered to all of them and hair samples were collected before the administration of the single dose and other two samples were collected one month and two months later, respectively. The segmental analysis of the latter two samples allowed us to calculate two ratios: 4.45:1 (95% C.I. 3.52-5.63) and 3.35:1 (95% C.I. 2.14-5.18), respectively, which can be recommended as reasonable values for a positive identification of GHB intake. Finally the method was applied to three real cases where a GHB single exposure probably occurred.

  7. 75 FR 53719 - Manufacturer of Controlled Substances; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-01

    ... registered as a bulk manufacturer of Gamma Hydroxybutyric Acid (GHB) (2010), a basic class of controlled substance listed in schedule I. The company plans to manufacture Gamma Hydroxybutyric Acid (GHB) (2010)...

  8. Club Drug Use

    MedlinePlus

    ... different from other illicit drugs?What are the dangers of taking club drugs?What can I do ... Drug Use | Gamma-Hydroxybutyrate (GHB)Learn about the dangers of taking gamma-hydroxybutyrate (GHB), an illegal drug ...

  9. Regional Fos-expression induced by γ-hydroxybutyrate (GHB): comparison with γ-butyrolactone (GBL) and effects of co-administration of the GABAB antagonist SCH 50911 and putative GHB antagonist NCS-382.

    PubMed

    van Nieuwenhuijzen, P S; McGregor, I S; Chebib, M; Hunt, G E

    2014-09-26

    γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. We also compare Fos expression caused by GHB and its precursor γ-butyrolactone (GBL), which is a pro-drug for GHB but lacks the high sodium content of the parent GHB molecule. Both GHB (1,000 mg/kg) and GBL (600 mg/kg) induced rapid sedation in rats that lasted over 90 min and caused similar Fos expression patterns, albeit with GBL causing greater activation of the nucleus accumbens (core and shell) and dentate gyrus (granular layer). Pretreatment with SCH 50911 (100mg/kg) partly reversed the sedative effects of GHB and significantly reduced GHB-induced Fos expression in only four regions: the tenia tecta, lateral habenula, dorsal raphe and laterodorsal tegmental nucleus. NCS-382 (50mg/kg) had no effect on GHB-induced sedation or Fos expression. When given alone, both NCS-382 and SCH 50911 increased Fos expression in the bed nucleus of the stria terminalis, central amygdala, parasubthalamic nucleus and nucleus of the solitary tract. SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors.

  10. Behavioral analyses of GHB: receptor mechanisms.

    PubMed

    Carter, Lawrence P; Koek, Wouter; France, Charles P

    2009-01-01

    GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABAB receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABAB receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABAA and GABAB receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects.

  11. Behavioral Analyses of GHB: Receptor Mechanisms

    PubMed Central

    Carter, Lawrence P.; Koek, Wouter; France, Charles P.

    2009-01-01

    GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABAB receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABAB receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABAA and GABAB receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects. PMID:19010351

  12. GHB. Club drug or confusing artifact?

    PubMed

    Karch, S B; Stephens, B G; Nazareno, G V

    2001-09-01

    GHB can be produced either as a pre- or postmortem artifact. The authors describe two cases in which GHB was detected and discuss the problem of determining the role of GHB in each case. In both cases, NaF-preserved blood and urine were analyzed using gas chromatography. The first decedent, a known methamphetamine abuser, had GHB concentrations similar to those observed with subanesthetic doses (femoral blood, 159 microg/ml; urine, 1100 microg/ml). Myocardial fibrosis, in the pattern associated with stimulant abuse, was also evident. The second decedent had a normal heart but higher concentrations of GHB (femoral blood, 1.4 mg/ml; right heart, 1.1 mg/ml; urine, 6.0 mg/ml). Blood cocaine and MDMA levels were 420 and 730 ng/ml, respectively. Both decedents had been drinking and were in a postabsorptive state, with blood to vitreous ratios of less than 0.90. If NaF is not used as a preservative, GHB is produced as an artifact. Therefore, the mere demonstration of GHB does not prove causality or even necessarily that GHB was ingested. Blood and urine GHB concentrations in case 1 can be produced by a therapeutic dose of 100 mg, and myocardial fibrosis may have had more to do with the cause of death than GHB. The history in case 2 is consistent with the substantial GHB ingestion, but other drugs, including ethanol, were also detected. Ethanol interferes with GHB metabolism, preventing GHB breakdown, raising blood concentrations, and making respiratory arrest more likely. Combined investigational, autopsy, and toxicology data suggest that GHB was the cause of death in case 2 but not case 1. Given the recent discovery that postmortem GHB production occurs even in stored antemortem blood samples (provided they were preserved with citrate) and the earlier observations that de novo GHB production in urine does not occur, it is unwise to draw any inferences about causality unless (1) blood and urine are both analyzed and found to be elevated; (2) blood is collected in Na

  13. GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome.

    PubMed

    Busardò, Francesco P; Jones, Alan W

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  14. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

    PubMed Central

    Busardò, Francesco P.; Jones, Alan W.

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  15. What You Need to Know about Drugs: GHB

    MedlinePlus

    ... What Happens in the Operating Room? What You Need to Know About Drugs: GHB KidsHealth > For Kids > What You Need to Know About Drugs: GHB Print A A ... hallucinations. GHB has caused many young people to need emergency medical care. Because the liquid is odorless ...

  16. 78 FR 9397 - International Drug Scheduling; Convention on Psychotropic Substances; World Health Organization...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ... Substances; World Health Organization Scheduling Recommendations for Gamma-hydroxybutyric Acid AGENCY: Food...), has notified the Secretary-General that it is of the opinion that Gamma- hydroxybutyric acid (GHB... control of y-hydroxybutyric acid (GHB). The recommendation is that GHB be rescheduled from Schedule IV...

  17. GHB for cataplexy: Possible mode of action.

    PubMed

    Szabadi, Elemer

    2015-06-01

    The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (γ-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to 'heterologous denervation supersensitivity' resulting from the loss/weakening of the orexinergic input to the LC. This would lead to the sensitization of the autoinhibition mechanism of LC neurones mediated by inhibitory alpha-2 adrenoceptors ('autoreceptors'). Thus the excitatory input from the amygdala to the LC, activated by an emotional stimulus, would lead to the 'switching off' of LC activity via the supersensitive auto-inhibition mechanism. GHB is an agonist at both γ-aminobutyric acid (GABA) GABA (B) and GHB receptors that may be a subtype of an extrasynaptic GABA(A) receptor. GHB may prevent a cataplectic attack by dampening the tone of LC neurones via the stimulation of inhibitory extrasynaptic GABA receptors in the LC, and thus increasing the threshold for autoinhibition.

  18. Long-term γ-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics.

    PubMed

    Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

    2011-07-01

    Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

  19. Long-Term γ-Hydroxybutyric Acid (GHB) and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics

    PubMed Central

    Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell’Osso, Liliana; Maremmani, Icro

    2011-01-01

    Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis. PMID:21845160

  20. γ-Hydroxybutyrate (GHB)-induced respiratory depression: combined receptor-transporter inhibition therapy for treatment in GHB overdose.

    PubMed

    Morse, Bridget L; Vijay, Nisha; Morris, Marilyn E

    2012-08-01

    Overdose of γ-hydroxybutyrate (GHB) frequently causes respiratory depression, occasionally resulting in death; however, little is known about the dose-response relationship or effects of potential overdose treatment strategies on GHB-induced respiratory depression. In these studies, the parameters of respiratory rate, tidal volume, and minute volume were measured using whole-body plethysmography in rats administered GHB. Intravenous doses of 200, 600, and 1500 mg/kg were administered to assess the dose-dependent effects of GHB on respiration. To determine the receptors involved in GHB-induced respiratory depression, a specific GABA(B) receptor antagonist, (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), and a specific GABA(A) receptor antagonist, bicuculline, were administered before GHB. The potential therapeutic strategies of receptor inhibition and monocarboxylate transporter (MCT) inhibition were assessed by inhibitor administration 5 min after GHB. The primary effect of GHB on respiration was a dose-dependent decrease in respiratory rate, accompanied by an increase in tidal volume, resulting in little change in minute volume. Pretreatment with 150 mg/kg SCH50911 completely prevented the decrease in respiratory rate, indicating agonism at GABA(B) receptors to be primarily responsible for GHB-induced respiratory depression. Administration of 50 mg/kg SCH50911 after GHB completely reversed the decrease in respiratory rate; lower doses had partial effects. Administration of the MCT inhibitor l-lactate increased GHB renal and total clearance, also improving respiratory rate. Administration of 5 mg/kg SCH50911 plus l-lactate further improved respiratory rate compared with the same dose of either agent alone, indicating that GABA(B) and MCT inhibitors, alone and in combination, represent potential treatment options for GHB-induced respiratory depression.

  1. Possible long-term effects of γ-hydroxybutyric acid (GHB) due to neurotoxicity and overdose.

    PubMed

    van Amsterdam, Jan G C; Brunt, Tibor M; McMaster, Minni T B; Niesink, Raymond J M

    2012-04-01

    In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory.

  2. Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats.

    PubMed

    Pedraza, Carmen; García, Francisca Belén; Navarro, José Francisco

    2009-10-01

    Gammahydroxybutyric acid (GHB) is an endogenous constituent of the central nervous system that has acquired great social relevance for its use as a recreational 'club drug'. GHB, popularly known as 'liquid ecstasy', is addictive when used continuously. Although the symptoms associated with acute intoxication are well known, the effects of prolonged use remain uncertain. We examined in male rats the effect of repeated administration of GHB (10 and 100 mg/kg) on various parameters: neurological damage, working memory and spatial memory, using neurological tests, the Morris water maze and the hole-board test. The results showed that repeated administration of GHB, especially at doses of 10 mg/kg, causes neurological damage, affecting the 'grasping' reflex, as well as alteration in spatial and working memories. Stereological quantification showed that this drug produces a drastic neuronal loss in the CA1 hippocampal region and in the prefrontal cortex, two areas clearly involved in cognitive and neurological functions. No effects were noted after quantification in the periaqueductal grey matter (PAG), a region lacking GHB receptors. Moreover, NCS-382, a putative antagonist of GHB receptor, prevented both neurological damage and working- memory impairment induced by GHB. This suggests that the effects of administration of this compound may be mediated, at least partly, by specific receptors in the nervous system. The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects. This is very relevant because its abuse, especially by young persons, could produce considerable neurological alterations after prolonged abuse.

  3. Reconsidering GHB: orphan drug or new model antidepressant?

    PubMed

    Bosch, Oliver G; Quednow, Boris B; Seifritz, Erich; Wetter, Thomas C

    2012-05-01

    For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders.

  4. GHB-Induced Cognitive Deficits During Adolescence and the Role of NMDA Receptor.

    PubMed

    Sircar, R; Wu, L-C; Reddy, K; Sircar, D; Basak, A K

    2011-03-01

    We have earlier reported that γ-hydroxybutyric acid (GHB) disrupts the acquisition of spatial learning and memory in adolescent rats. GHB is known to interact with several neurotransmitter systems that have been implicated in cognitive functioning. The N-methyl-D-aspartate receptor (NR) -type of glutamate receptor is considered to be an important target for spatial learning and memory. Molecular mechanisms governing the neuroadptations following repeated GHB treatment in adolecent rats remain unknown. We examined the role of NMDA receptor in adolescent GHB-induced cognitive deficit. Adolescent rats were administered with GHB on 6 consecutive days, and surface-expressed NMDA receptor subunits levels were measured. GHB significantly decreased NR1 levels in the frontal cortex. Adolescent GHB also significantly reduced cortical NR2A subunit levels. Our findings support the hypothesis that adolescent GHB-induced cogntive deficits are associated with neuroadaptations in glutamatergic transmission, particulaly NR functioning in the frontal cortex.

  5. GHB receptor targets in the CNS: focus on high-affinity binding sites.

    PubMed

    Bay, Tina; Eghorn, Laura F; Klein, Anders B; Wellendorph, Petrine

    2014-01-15

    γ-Hydroxybutyric acid (GHB) is an endogenous compound in the mammalian brain with both low- and high-affinity receptor targets. GHB is used clinically in the treatment of symptoms of narcolepsy and alcoholism, but also illicitly abused as the recreational drug Fantasy. Major pharmacological effects of exogenous GHB are mediated by GABA subtype B (GABAB) receptors that bind GHB with low affinity. The existence of GHB high-affinity binding sites has been known for more than three decades, but the uncovering of their molecular identity has only recently begun. This has been prompted by the generation of molecular tools to selectively study high-affinity sites. These include both genetically modified GABAB knock-out mice and engineered selective GHB ligands. Recently, certain GABA subtype A (GABAA) receptor subtypes emerged as high-affinity GHB binding sites and potential physiological mediators of GHB effects. In this research update, a description of the various reported receptors for GHB is provided, including GABAB receptors, certain GABAA receptor subtypes and other reported GHB receptors. The main focus will thus be on the high-affinity binding targets for GHB and their potential functional roles in the mammalian brain.

  6. Risk assessment of GBL as a substitute for the illicit drug GHB in the Netherlands. A comparison of the risks of GBL versus GHB.

    PubMed

    van Amsterdam, Jan; Brunt, Tibor; Pennings, Ed; van den Brink, Wim

    2014-11-01

    In the Netherlands, γ-hydroxybutyric acid (GHB) was recently banned, but γ-butyrolactone (GBL) was not. As such, GBL remained a legal alternative to GHB. This review compares the risks of GBL and GHB. Pure GBL is per unit of volume about threefold stronger and therefore threefold more potent than currently used GHB-preparations in the Netherlands. Like GHB, GBL use hardly leads to organ toxicity, although, as with GHB, frequent GBL use may lead to repeated comas that may result in residual impairments in cognitive function and memory. Little is known about the prevalence of GBL use in Europe, but the recent increase in improper trading in GBL confirms that users of GHB gradually switch to the use of GBL. This shift may result in an increase in the number GBL dependent users, because the dependence potential of GBL is as great as that of GHB. Severe withdrawal symptoms and a high relapse rate are seen following cessation of heavy GBL use. GBL-dependent users seem to be severe (dependent, problematic) GHB users who started using GBL, the legal GHB substitute. Subjects who are solely dependent to GBL are rarely reported. About 5-10% of the treatment seeking GHB dependent subjects also use GBL and this subpopulation forms a vulnerable group with multiple problems. Fatal accidents with GBL are rarely reported, but non-fatal GHB (or GBL) overdoses frequently occur for which supportive treatment is needed. It is recommended to monitor the recreational use of GBL, the rate of GBL dependence treatment, and the improper trading of GBL.

  7. γ-Hydroxybutyric acid (GHB) is not an agonist of extrasynaptic GABAA receptors.

    PubMed

    Connelly, William M; Errington, Adam C; Crunelli, Vincenzo

    2013-01-01

    γ-Hydroxybutyric acid (GHB) is an endogenous compound and a drug used clinically to treat the symptoms of narcolepsy. GHB is known to be an agonist of GABAB receptors with millimolar affinity, but also binds with much higher affinity to another site, known as the GHB receptor. While a body of evidence has shown that GHB does not bind to GABAA receptors widely, recent evidence has suggested that the GHB receptor is in fact on extrasynaptic α4β1δ GABAA receptors, where GHB acts as an agonist with an EC50 of 140 nM. We investigated three neuronal cell types that express a tonic GABAA receptor current mediated by extrasynaptic receptors: ventrobasal (VB) thalamic neurons, dentate gyrus granule cells and striatal medium spiny neurons. Using whole-cell voltage clamp in brain slices, we found no evidence that GHB (10 µM) induced any GABAA receptor mediated current in these cell types, nor that it modulated inhibitory synaptic currents. Furthermore, a high concentration of GHB (3 mM) was able to produce a GABAB receptor mediated current, but did not induce any other currents. These results suggest either that GHB is not a high affinity agonist at native α4β1δ receptors, or that these receptors do not exist in classical areas associated with extrasynaptic currents.

  8. Phenotypic and chemotypic studies using Arabidopsis and yeast reveal that GHB converts to SSA and induce toxicity.

    PubMed

    Mekonnen, Dereje Worku; Ludewig, Frank

    2016-07-01

    γ-Hydroxybutyric acid (GHB) is a naturally occurring compound. It is detected in organisms such as yeasts, plants and mammals. GHB is produced from the reduction of succinic semialdehyde (SSA) by the activity of GHB dehydrogenase. Arabidopsis genome contains two GHB dehydrogenase encoding genes. The accumulation of GHB in ssadh mutants led to the speculation that GHB is the cause of aberrant phenotypes. Conversely, the accumulation of GHB in Arabidopsis plants subjected to abiotic stresses was described as a way of avoiding SSA induced damage. To resolve these contrasting views on GHB, we examined the effect of exogenous GHB and SSA on the growth of yeast and Arabidopsis plants. GHB concentrations up to 1.5 mM didn't affect shoots of Arabidopsis plants; however, root growth was inhibited. In contrast, 0.3 mM SSA has severely affected the growth of plants. Treatment of yeast wild-type strain with 10 mM SSA and 10 mM GHB didn't affect the growth. However, the growth of yeast uga2 mutant was greatly inhibited by the same concentration of SSA, but not GHB. Metabolic analysis and enzyme activity assay on native gel showed that Arabidopsis, but not yeast, possesses a GHB dehydrogenase activity that converts GHB back to SSA. The enzymatic assay has also indicated the existence of an additional GHB dehydrogenase encoding gene(s) in Arabidopsis genome. Taken together, we conclude that GHB is less toxic than SSA. Its accumulation in ssadh mutants and during abiotic stresses is a response to avoid the SSA induced damage.

  9. GHb level and subsequent mortality among adults in the U.S.

    PubMed

    Saydah, Sharon; Tao, Min; Imperatore, Giuseppina; Gregg, Edward

    2009-08-01

    OBJECTIVE To examine the association of hyperglycemia, as measured by GHb, with subsequent mortality in a nationally representative sample of adults. RESEARCH DESIGN AND METHODS We included adults aged > or =20 years who participated in Third National Health and Nutrition Examination Survey (1988-1994) and had complete information, including baseline diabetes status by self-report and measured GHb (n = 19,025) and follow-up through the end of 2000 for mortality. RESULTS In the overall population, higher levels of GHb were associated with increased risk of mortality from all causes, heart disease, and cancer. After adjustment for potential risk factors, the relative hazard (RH) for adults with GHb > or =8% compared with adults with GHb <6% was 2.59 (95% CI 1.88-3.56) for all-cause mortality, 3.38 (1.98-5.77) for heart disease mortality, and 2.64 (1.17-5.97) for cancer mortality. Among adults with diagnosed diabetes, having GHb > or =8% compared with GHb <6% was associated with higher all-cause mortality (RH 1.68, 95% CI 1.03-2.74) and heart disease mortality (2.48, 1.09-5.64), but there was no increased risk of cancer mortality by GHb category. Among adults without diagnosed diabetes, there was no significant association of all-cause, heart disease, or cancer mortality and GHb category. CONCLUSIONS These results highlight the importance of GHb levels in mortality risk among a nationally representative sample of adults with and without diagnosed diabetes and indicate that higher levels are associated with increased mortality in adults with diabetes.

  10. Drug facilitated sexual assault with lethal outcome: GHB intoxication in a six-year-old girl.

    PubMed

    Mehling, Lena-Maria; Johansen, Sys Stybe; Wang, Xin; Doberentz, Elke; Madea, Burkhard; Hess, Cornelius

    2016-02-01

    A very serious case of DFSA (drug facilitated sexual assault) is presented, in which a six-year-old girl died following sedation with γ-hydroxybutyric acid (GHB). She had been sexually abused by a relative. Samples of cardiac blood, bile, vitreous humour, liver, kidney, brain tissues and hair were analysed by a LC-MS/MS method. The following GHB concentrations were determined: cardiac blood: 150 mg/l; bile: 292mg/l; vitreous humour: 58mg/l; liver: 100 mg/kg; kidney: 124.5 mg/kg, brain: 110 mg/kg. Very high GHB levels were found in the proximal part of the hair sample (about 40.9 ng/mg). In distal segments of hair - up to 12 cm distant from the hair scalp - GHB concentrations were higher than the overall found endogenous range of 2-3 ng/mg. Police investigations revealed that the uncle had also administered GHB to the older half-sister. Therefore, a sample of her hair was analysed accordingly, but unremarkable results were obtained. Comparing our toxicological results with police investigations and the offender's statements it can be assumed that the 6-year-old girl had ingested GHB. By exclusion of other causes of death a lethal intoxication with GHB could be confirmed.

  11. Ultra-high-performance liquid chromatography tandem mass spectrometry determination of GHB, GHB-glucuronide in plasma and cerebrospinal fluid of narcoleptic patients under sodium oxybate treatment.

    PubMed

    Tittarelli, Roberta; Pichini, Simona; Pedersen, Daniel S; Pacifici, Roberta; Moresco, Monica; Pizza, Fabio; Busardò, Francesco Paolo; Plazzi, Giuseppe

    2017-01-25

    Sodium oxybate (Xyrem(®)), the sodium salt of γ- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) validated method, GHB was determined together with its glucuronide (GHB-gluc), in plasma and cerebrospinal fluid (CSF) samples of NT1 patients under sodium oxybate treatment. To characterize the plasma pharmacokinetics of GHB, three subjects with NT1 were administered at time 0 and 4h with 1.25, 1.5 and 3.55g Xyrem(®), respectively and had their blood samples collected at 7 time points throughout an 8-h session. CSF specimens, collected for orexin A measurement from the same three subjects 6h after their second administration, were also tested. The results obtained suggested that GHB plasma values increased disproportionally with the rising doses, (Cmax0-4: 12.53, 32.95 and 69.62μg/mL; Cmax4-8: 44.93, 75.03 and 111.93μg/mL for total Xyrem(®) dose of 2.5, 3 and 7g respectively) indicating non-linear dose-response. GHB-Gluc was present only in traces in all plasma samples from treated patients, not changing with increasing Xyrem(®) doses. GHB values of 5.62, 6.10 and 17.74μg/mL for 2, 3 and 7g Xyrem(®) were found in CSF with a significant difference from control values. GHB-Gluc was found in negligible concentrations with no differences to those of control individuals. In conclusion this simple and fast UHPLC-MS/MS method proved useful for pharmacokinetic studies and therapeutic drug monitoring of GHB in narcoleptic patients treated with sodium oxybate.

  12. Pharmacokinetic properties of γ-hydroxybutyrate (GHB) in whole blood, serum, and urine.

    PubMed

    Brailsford, Alan D; Cowan, David A; Kicman, Andrew T

    2012-03-01

    Over the last 10-15 years, γ-hydroxybutyrate (GHB) and γ-butyrolactone have become increasingly popular "club drugs", but they have also gained attention as potential agents of drug-facilitated sexual assault (DFSA). Several studies have attempted to characterize GHB's pharmacokinetic properties in humans, and the aim of this paper is to build on this research with an emphasis on DFSA cases. A 25 mg/kg dose of GHB was given to 12 GHB-naïve volunteers (6 men and 6 women). Urine and blood samples (serum and whole blood) were collected and analyzed by gas chromatography-mass spectrometry following liquid-liquid extraction. The urinary T(max) was 1 h in 11 volunteers with a mean C(max) of 67.6 mg/L (32.6-161.3 mg/L). Urinary concentrations rapidly decreased to < 10 mg/L (interpretive limit) for 11 volunteers after just 4 h. Data derived from whole blood (mean C(max) = 48.0 mg/L, T(max) = 24.6 min) closely matched that from serum (mean C(max) = 59.4 mg/L, T(max) = 23.3 min), suggesting GHB is distributed into erythrocytes. All 12 volunteers had GHB concentrations of less than 5 mg/L in both whole blood and serum after 3 h. Results verify the rapid elimination of GHB and the limited retrospective power of a concentration-based approach to prove GHB administration in blood and urine and confirm that, in DFSA cases, samples should be collected as soon as possible.

  13. Trends in γ-Hydroxybutyrate (GHB) and Related Drug Intoxication: 1999 to 2003

    PubMed Central

    Anderson, Ilene B.; Kim, Susan Y.; Dyer, Jo Ellen; Burkhardt, Cindy B.; Iknoian, Jayme C.; Walsh, Michael J.; Blanc, Paul D.

    2008-01-01

    Study objective To analyze changes in γ-hydroxybutyrate (GHB) case reporting, we review GHB or congener drug cases reported to the California Poison Control System, comparing these to other data sets. Methods We identified cases from the California Poison Control System computerized database using standardized codes and key terms for GHB and congener drugs (“gamma butyrolactone,” “1,4-butanediol,” “gamma valerolactone”). We noted California Poison Control System date, caller and exposure site, patient age and sex, reported coingestions, and outcomes. We compared California Poison Control System data to case incidence from American Association of Poison Control Centers and Drug Abuse Warning Network data and drug use prevalence from National Institute for Drug Abuse survey data. Results A total of 1,331 patients were included over the 5-year period (1999-2003). California Poison Control System–reported GHB exposures decreased by 76% from baseline (n=426) to the final study year (n=101). The absolute decrease was present across all case types, although there was a significant proportional decrease in routine drug abuse cases and an increase in malicious events, including GHB-facilitated sexual assault (P=.002). American Association of Poison Control Centers data showed a similar decrease from 2001 to 2003. Drug Abuse Warning Network incidence flattened from 2001 to 2002 and decreased sharply in 2003. National Institute for Drug Abuse survey time trends were inconsistent across age groups. Conclusion Based on the precipitous decrease in California Poison Control System case incidence for GHB during 5 years, the parallel trend in American Association of Poison Control Centers data, and a more recent decrease in Drug Abuse Warning Network cases, a true decrease in case incidence is likely. This could be due to decreased abuse rates or because fewer abusers seek emergency medical care. Case reporting may account for part of the decrease in the incidence of

  14. Determination of GHB levels in breast milk and correlation with blood concentrations.

    PubMed

    Busardò, Francesco Paolo; Bertol, Elisabetta; Mannocchi, Giulio; Tittarelli, Roberta; Pantano, Flaminia; Vaiano, Fabio; Baglio, Giovanni; Kyriakou, Chrystalla; Marinelli, Enrico

    2016-08-01

    The sodium salt of GHB or sodium oxybate is approved and registered in some countries as a therapeutic substance (Xyrem(®)) for the treatment of narcolepsy-associated cataplexy. This study was designed to measure the GHB endogenous levels in blood and breast milk of 20 breastfeeding women. In addition, blood and breast milk samples of a 32-year-old narcoleptic nursing mother, who was on sodium oxybate treatment, were simultaneously collected at 0.5, 1, 3, 4 and 5h following a 4.5g GHB dose and analyzed, in order to establish the safety interval of time to breastfeed. A GC-MS method for the detection and quantification of GHB in blood and breast milk was developed and fully validated. The geometric mean of endogenous GHB levels in blood and breast milk detected at time 0 were 0.57mg/L; 95% Reference Interval (RI): 0.21-1.52mg/L and 0.36mg/L; 95% RI: 0.13-1.03mg/L, respectively. The geometric mean of the concentration of GHB in milk was 37% less (95% RI: from 14 to 53%) compared to that found in the blood. The analysis of blood and breast milk samples collected from the 32 years-old female showed the following results: GHB blood concentration 0.5h after medication intake was 80.10mg/L, reaching the peak 1h after the drug administration (108.34mg/L) and it steadily decreased to reach a level of 1.75mg/L, 5h after the medication intake. The GHB concentration found in breast milk followed the same pattern as for the blood, with the highest concentration being 23.19mg/L, 1h after sodium oxybate administration and the lowest 0.99mg/L, 5h after the medication's intake. The comparison between blood and breast milk GHB levels in the 32-year-old woman, showed significant lower GHB levels in milk at 0.5, 1 and 3h, ranging from 71 to 80% less. It is interesting to note that only at 4 and 5h the difference between blood and breast milk GHB levels fell within the 95% RI (14-53%) of endogenous levels. Taking into consideration the absence of reference values for endogenous GHB in

  15. α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB).

    PubMed

    Absalom, Nathan; Eghorn, Laura F; Villumsen, Inge S; Karim, Nasiara; Bay, Tina; Olsen, Jesper V; Knudsen, Gitte M; Bräuner-Osborne, Hans; Frølund, Bente; Clausen, Rasmus P; Chebib, Mary; Wellendorph, Petrine

    2012-08-14

    γ-Hydroxybutyric acid (GHB) binding to brain-specific high-affinity sites is well-established and proposed to explain both physiological and pharmacological actions. However, the mechanistic links between these lines of data are unknown. To identify molecular targets for specific GHB high-affinity binding, we undertook photolinking studies combined with proteomic analyses and identified several GABA(A) receptor subunits as possible candidates. A subsequent functional screening of various recombinant GABA(A) receptors in Xenopus laevis oocytes using the two-electrode voltage clamp technique showed GHB to be a partial agonist at αβδ- but not αβγ-receptors, proving that the δ-subunit is essential for potency and efficacy. GHB showed preference for α4 over α(1,2,6)-subunits and preferably activated α4β1δ (EC(50) = 140 nM) over α4β(2/3)δ (EC(50) = 8.41/1.03 mM). Introduction of a mutation, α4F71L, in α4β1(δ)-receptors completely abolished GHB but not GABA function, indicating nonidentical binding sites. Radioligand binding studies using the specific GHB radioligand [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid showed a 39% reduction (P = 0.0056) in the number of binding sites in α4 KO brain tissue compared with WT controls, corroborating the direct involvement of the α4-subunit in high-affinity GHB binding. Our data link specific GHB forebrain binding sites with α4-containing GABA(A) receptors and postulate a role for extrasynaptic α4δ-containing GABA(A) receptors in GHB pharmacology and physiology. This finding will aid in elucidating the molecular mechanisms behind the proposed function of GHB as a neurotransmitter and its unique therapeutic effects in narcolepsy and alcoholism.

  16. A surrogate analyte-based LC-MS/MS method for the determination of γ-hydroxybutyrate (GHB) in human urine and variation of endogenous urinary concentrations of GHB.

    PubMed

    Kang, Soyoung; Oh, Seung Min; Chung, Kyu Hyuck; Lee, Sooyeun

    2014-09-01

    γ-Hydroxybutyrate (GHB) is a drug of abuse with a strong anesthetic effect; however, proving its ingestion through the quantification of GHB in biological specimens is not straightforward due to the endogenous presence of GHB in human blood, urine, saliva, etc. In the present study, a surrogate analyte approach was applied to accurate quantitative determination of GHB in human urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to overcome this issue. For this, (2)H6-GHB and (13)C2-dl-3-hydroxybutyrate were used as a surrogate standard and as an internal standard, respectively, and parallelism between the surrogate analyte approach and standard addition was investigated at the initial step. The validation results proved the method to be selective, accurate, and precise, with acceptable linearity within calibration ranges (0.1-1μg/ml). The limit of detection and the limit of quantification of (2)H6-GHB were 0.05 and 0.1μg/ml, respectively. No significant variations were observed among urine matrices from different sources. The stability of (2)H6-GHB was satisfactory under sample storage and in-process conditions. However, in vitro production of endogenous GHB was observed when the urine sample was kept under the in-process condition for 4h and under the storage conditions of 4 and -20°C. In order to facilitate the practical interpretation of urinary GHB, endogenous GHB was accurately measured in urine samples from 79 healthy volunteers using the surrogate analyte-based LC-MS/MS method developed in the present study. The unadjusted and creatinine-adjusted GHB concentrations in 74 urine samples with quantitative results ranged from 0.09 to 1.8μg/ml and from 4.5 to 530μg/mmol creatinine, respectively. No significant correlation was observed between the unadjusted and creatinine-adjusted GHB concentrations. The urinary endogenous GHB concentrations were affected by gender and age while they were not significantly influenced by habitual

  17. Drug-Facilitated Sexual Assault on Campus: Challenges and Interventions.

    ERIC Educational Resources Information Center

    Hensley, Laura G.

    2002-01-01

    The use of gamma-hydroxybutyric acid (GHB) to facilitate sexual assault is increasing on campuses nationwide. This article provides college counselors with an overview of the use of GHB in campus sexual assault, outlines suggestions for crisis intervention, and discusses the challenges of counseling survivors of drug-facilitated sexual assault.…

  18. Anion exchange SPE and liquid chromatography-tandem mass spectrometry in GHB analysis.

    PubMed

    Elian, Albert A; Hackett, Jeffery

    2011-12-01

    In this study, the extraction of γ-hydroxybutyrate (GHB) from urine using solid-phase extraction (SPE) is described. SPE was performed on anion exchange columns after samples of urine had been diluted with de-ionized water. After application of the diluted samples containing GHB-d(6) as an internal standard, the sorbent was washed with deionized water and methanol and dried. The GHB was eluted from the SPE column with a solvent consisting of methanol containing 6% glacial acetic acid. The eluent was collected, evaporated to dryness, and dissolved in mobile phase (100 μL) for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in negative multiple reaction monitoring (MRM) mode. Liquid chromatography was performed in gradient mode employing a biphenyl column and a mobile phase consisting of acetontitrile (containing 0.1% formic acid) and 0.1% aqueous formic acid. The total run time for each analysis was less than 5 min. The limits of detection/quantification for this method were determined to be 50 and 100 ng/mL, respectively. The method was found to be linear from 500 ng/mL to 10,000 ng/mL (r(2)>0.995). The recovery of GHB was found to be greater than 75%. In this report, results of authentic urine samples analyzed for GHB by this method are presented. GHB concentrations in these samples were found to be range from less than 500 ng/mL to 5110 ng/mL.

  19. Stability of endogenous GHB in vitreous humor vs peripheral blood in dead bodies.

    PubMed

    Busardò, Francesco Paolo; Mannocchi, Giulio; Giorgetti, Raffaele; Pellegrini, Manuela; Baglio, Giovanni; Zaami, Simona; Marinelli, Enrico; Pichini, Simona

    2016-12-26

    For the first time, the stability of GHB was tested in post-mortem peripheral blood and vitreous humor samples, collected from 22 dead bodies at two different times: at the external body examination at the place of death and then during autopsy. An ad hoc method for the detection and quantification of GHB in vitreous humor by gas chromatography coupled to mass spectrometry (GC-MS) was developed and validated, with a good linearity between 0.1 and 50μg/mL (r(2)=0.991) and a precision and accuracy always better than 10% and an analytical recovery higher than 90%. The geometric mean of GHB concentration in the 22 peripheral blood samples at t0 was: 3.6μg/mL (95% CI: 2.3-5.9μg/mL) and at t1 it was 7.4μg/mL (95% CI: 5.0-10.9μg/mL); that of GHB in the 22 vitreous humor at t0 was: 2.5μg/mL (95% CI: 1.5-4.1μg/mL) and at t1 it was 3.0μg/mL (95% CI: 1.9-4.8μg/mL). There was no significant difference between the GHB concentrations in vitreous humor and peripheral blood at t0 in all the samples (p>0.10). Conversely at t1, the increase of GHB in the peripheral blood was significantly increased by a 102% (range: 86-120%) (p<0.001 vs t0), while in the vitreous humor only a slight increase by 19% was observed (range: 16-21%) (p>0.05 vs t0). Finally at t1, GHB values in the two matrices were statistically different, being that of peripheral blood higher (p<0.01). This study demonstrated the usefulness of vitreous humor as a more stable alternative matrix in comparison to peripheral blood for the post-mortem determination of endogenous GHB.

  20. Autoradiographic imaging and quantification of the high-affinity GHB binding sites in rodent brain using (3)H-HOCPCA.

    PubMed

    Klein, A B; Bay, T; Villumsen, I S; Falk-Petersen, C B; Marek, A; Frølund, B; Clausen, R P; Hansen, H D; Knudsen, G M; Wellendorph, P

    2016-11-01

    GHB (γ-hydroxybutyric acid) is a compound endogenous to mammalian brain with high structural resemblance to GABA. GHB possesses nanomolar-micromolar affinity for a unique population of binding sites, but the exact nature of these remains elusive. In this study we utilized the highly selective GHB analogue, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) as a tritiated version ((3)H-HOCPCA) to radioactively label the specific GHB high-affinity binding site and gain further insight into the density, distribution and developmental profile of this protein. We show that, in low nanomolar concentrations, (3)H-HOCPCA displays excellent signal-to-noise ratios using rodent brain autoradiography, which makes it a valuable ligand for anatomical quantification of native GHB binding site levels. Our data confirmed that (3)H-HOCPCA labels only the high-affinity specific GHB binding site, found in high density in cortical and hippocampal regions. The experiments revealed markedly stronger binding at pH 6.0 (Kd 73.8 nM) compared to pH 7.4 (Kd 2312 nM), as previously reported for other GHB radioligands but similar Bmax values. Using (3)H-HOCPCA we analyzed the GHB binding protein profile during mouse brain development. Due to the high sensitivity of this radioligand, we were able to detect low levels of specific binding already at E15 in mouse brain, which increased progressively until adulthood. Collectively, we show that (3)H-HOCPCA is a highly sensitive radioligand, offering advantages over the commonly used radioligand (3)H-NCS-382, and thus a very suitable in vitro tool for qualitative and quantitative autoradiography of the GHB high-affinity site.

  1. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma.

    PubMed

    El-Habr, Elias A; Dubois, Luiz G; Burel-Vandenbos, Fanny; Bogeas, Alexandra; Lipecka, Joanna; Turchi, Laurent; Lejeune, François-Xavier; Coehlo, Paulo Lucas Cerqueira; Yamaki, Tomohiro; Wittmann, Bryan M; Fareh, Mohamed; Mahfoudhi, Emna; Janin, Maxime; Narayanan, Ashwin; Morvan-Dubois, Ghislaine; Schmitt, Charlotte; Verreault, Maité; Oliver, Lisa; Sharif, Ariane; Pallud, Johan; Devaux, Bertrand; Puget, Stéphanie; Korkolopoulou, Penelope; Varlet, Pascale; Ottolenghi, Chris; Plo, Isabelle; Moura-Neto, Vivaldo; Virolle, Thierry; Chneiweiss, Hervé; Junier, Marie-Pierre

    2017-04-01

    Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten-eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity.

  2. Determination of endogenous levels of GHB in human hair. Are there possibilities for the identification of GHB administration through hair analysis in cases of drug-facilitated sexual assault?

    PubMed

    Goullé, Jean Pierre; Chèze, Marjorie; Pépin, Gilbert

    2003-01-01

    We have developed a GC-MS-MS assay for GHB in human hair. Five milligrams of washed hair were hydrolyzed by 1M or 0.01M NaOH before a liquid-liquid extraction with ethyl acetate under acidic conditions. GHB-d(6) was used as the internal standard. TMS derivatives were formed before injection. TBDMS derivatives were used in cases of strong chromatographic interferences or in a confirmatory procedure. Analysis of basal levels of GHB in 61 drug-free donors gave the following results: the mean measured concentration for blond hair was 0.60 ng/mg (n = 12), SD = 0.19 ng/mg, and extreme figures were in the range 0.35-0.95 ng/mg. For brown hair, the mean measured concentration was 0.90 ng/mg (n = 30), SD = 0.42 ng/mg, and extreme figures 0.41-1.86 ng/mg. For black hair, the mean measured concentration was 0.90 ng/mg (n = 19), SD = 0.37 ng/mg, and extreme figures 0.32-1.54 ng/mg, showing no significant differences depending on hair color. Analysis of basal levels of GHB of 12 or more specimens in segmented hair showed a mean concentration of 1.22 ng/mg (0.31-8.4 ng/mg) and a relative standard deviation for each individual ranging from 6.75% to 37.98%. GHB was administered to a healthy 53-year-old white male (light brown hair) at oral dosages of 30, 45, and 60 mg/kg. Beard hair was collected just before administration and 24 h after (and each day for one week for the last dose), and a 7.5-cm scalp hair lock was collected 7 days after the last dose. A rise in GHB concentration was observed in beard hair for the 45 and 60 mg/kg dosages with a maximum at 24 h, whereas no change was observed for the 30 mg/kg dosage. Scalp hair was segmented into 3-mm long segments. The three proximal last segments showed significantly (0.0005 < p < 0.005) different concentrations of GHB (1.22, 1.27, and 1.66 ng/mg, respectively) when compared with the basal physiological level of GHB in this same person (mean = 0.62 ng/mg, SD = 0.15 ng/mg). A case of daily GHB abuse during bodybuilding allowed us

  3. In vitro toxicological evaluation of NCS-382, a high-affinity antagonist of γ-hydroxybutyrate (GHB) binding.

    PubMed

    Vogel, K R; Ainslie, G R; Roullet, J-B; McConnell, A; Gibson, K M

    2017-01-22

    γ-Hydroxybutyric acid (GHB), a minor metabolite of the inhibitory neurotransmitter GABA, can accumulate to significant concentrations in the heritable disorder of GABA degradation, succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD). Moreover, GHB may be employed in therapeutic settings (treatment of narcolepsy), as well as instances of illicit activity, including acquaintance sexual assault and the induction of euphoria. High-affinity binding sites for GHB in the brain have been identified, although the absolute identity of these receptors remains unclear. Pharmacological antagonism of GHB binding may have multiple instances of therapeutic relevance. The high affinity GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid) has not been piloted in humans. To address the potential clinical utility of NCS-382, we have piloted initial studies of its toxicology in HepG2 and primary hepatocyte cells. At high dose (0.5mM), NCS-382 showed no capacity for inhibition of microsomal CYPs (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and minimal potential for activation of xenobiotic nuclear receptors. Additional cellular integrity and functional assays (viability, oxidative stress, apoptosis, ATP production) revealed little evidence for cytotoxicity, and a low degree of dysregulation of >370 genes actively engaged in the mediation of cellular toxicity. In vitro testing indicates a low probability of cellular toxicity associated with NCS-382.

  4. Positive allosteric modulation of the GHB high-affinity binding site by the GABAA receptor modulator monastrol and the flavonoid catechin.

    PubMed

    Eghorn, Laura F; Hoestgaard-Jensen, Kirsten; Kongstad, Kenneth T; Bay, Tina; Higgins, David; Frølund, Bente; Wellendorph, Petrine

    2014-10-05

    γ-Hydroxybutyric acid (GHB) is a metabolite of γ-aminobutyric acid (GABA) and a proposed neurotransmitter in the mammalian brain. We recently identified α4βδ GABAA receptors as possible high-affinity GHB targets. GABAA receptors are highly sensitive to allosteric modulation. Thus to investigate whether GHB high-affinity binding sites are also sensitive to allosteric modulation, we screened both known GABAA receptor ligands and a library of natural compounds in the rat cortical membrane GHB specific high-affinity [3H]NCS-382 binding assay. Two hits were identified: Monastrol, a positive allosteric modulator of GABA function at δ-containing GABAA receptors, and the naturally occurring flavonoid catechin. These compounds increased [3H]NCS-382 binding to 185-272% in high micromolar concentrations. Monastrol and (+)-catechin significantly reduced [3H]NCS-382 dissociation rates and induced conformational changes in the binding site, demonstrating a positive allosteric modulation of radioligand binding. Surprisingly, binding of [3H]GHB and the GHB high-affinity site-specific radioligands [125I]BnOPh-GHB and [3H]HOCPCA was either decreased or only weakly increased, indicating that the observed modulation was critically probe-dependent. Both monastrol and (+)-catechin were agonists at recombinant α4β3δ receptors expressed in Xenopus laevis oocytes. When monastrol and GHB were co-applied no changes were seen compared to the individual responses. In summary, we have identified the compounds monastrol and catechin as the first allosteric modulators of GHB high-affinity binding sites. Despite their relatively weak affinity, these compounds may aid in further characterization of the GHB high-affinity sites that are likely to represent certain GABAA receptors.

  5. Club Drugs

    MedlinePlus

    ... Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known as Roofies Methamphetamine, also known as Speed, Ice, Chalk, Meth, Crystal, Crank, and Glass Lysergic Acid Diethylamide (LSD), also ...

  6. Pharmacokinetics of GHB and detection window in serum and urine after single uptake of a low dose of GBL - an experiment with two volunteers.

    PubMed

    Schröck, Alexandra; Hari, Yvonne; König, Stefan; Auwärter, Volker; Schürch, Stefan; Weinmann, Wolfgang

    2014-04-01

    During the last few years γ-hydroxybutyric acid (GHB) and γ-butyrolactone (GBL) have attracted much interest as recreational drugs and knock-out drops in drug-facilitated sexual assaults. This experiment aims at getting an insight into the pharmacokinetics of GHB after intake of GBL. Therefore Two volunteers took a single dose of 1.5 ml GBL, which had been spiked to a soft drink. Assuming that GBL was completely metabolized to GHB, the corresponding amount of GHB was 2.1 g. Blood and urine samples were collected 5 h and 24 h after ingestion, respectively. Additionally, hair samples (head hair and beard hair) were taken within four to five weeks after intake of GBL. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after protein precipitation with acetonitrile. The following observations were made: spiked to a soft drink, GBL, which tastes very bitter, formed a liquid layer at the bottom of the glass, only disappearing when stirring. Both volunteers reported weak central effects after approximately 15 min, which disappeared completely half an hour later. Maximum concentrations of GHB in serum were measured after 20 min (95 µg/ml and 106 µg/ml). Already after 4-5 h the GHB concentrations in serum decreased below 1 µg/ml. In urine maximum GHB concentrations (140 µg/ml and 120 µg/ml) were measured after 1-2 h, and decreased to less than 1 µg/ml within 8-10 h. The ratio of GHB in serum versus blood was 1.2 and 1.6.

  7. Comparison of the actions of gamma-butyrolactone and 1,4-butanediol in Swiss-Webster mice.

    PubMed

    de Fiebre, Christopher M; de Fiebre, Nancy Ellen C; Coleman, Scott L; Forster, Michael J

    2004-04-01

    The abuse of gamma-hydroxybutyrate (GHB) and two of its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are recognized as a public health concern. Here, we report dose-response and time-course analyses for effects of GBL and 1,4-BD on locomotor activity and body temperature in Swiss-Webster mice. Locomotor activity was measured for 2 h following a single injection of one of four doses of each agent plus a saline vehicle control. At 50 mg/kg, GBL produced an initial depression of locomotor activity which was followed by stimulation of locomotor activity. In contrast, 1,4-BD at 50 mg/kg stimulated locomotor activity without producing any depression of activity. At higher doses, GBL produced primarily a dose-dependent decrease in locomotor activity that returned to baseline within 50 min. In contrast, 1,4-BD produced an initial depression which was followed by stimulation of activity. Body temperature was measured rectally across a 2.5-h time course following injection with either agent. Both drugs produced hypothermia with peak effects occurring at 20 and 30 min for both drugs for the lower and higher dose, respectively. At 150 mg/kg, GBL produced a greater hypothermic response; however, no differences in hypothermic response were observed at 100 mg/kg. These studies demonstrate that the precursor drugs to GHB have some differential actions from each other.

  8. A novel quadruplex real-time PCR method for simultaneous detection of Cry2Ae and two genetically modified cotton events (GHB119 and T304-40)

    PubMed Central

    2014-01-01

    Background To date, over 150 genetically modified (GM) crops are widely cultivated. To comply with regulations developed for genetically modified organisms (GMOs), including labeling policies, many detection methods for GMO identification and quantification have been developed. Results To detect the entrance and exit of unauthorized GM crop events in China, we developed a novel quadruplex real-time PCR method for simultaneous detection and quantification of GM cotton events GHB119 and T304-40 in cotton-derived products (based on the 5′-flanking sequence) and the insect-resistance gene Cry2Ae. The limit of detection was 10 copies for GHB119 and Cry2Ae and 25 copies for T304-40. The limit of quantification was 25 copies for GHB119 and Cry2Ae and 50 copies for T304-40. Moreover, low bias and acceptable standard deviation and relative standard deviation values were obtained in quantification analysis of six blind samples containing different GHB119 and T304-40 ingredients. Conclusions The developed quadruplex quantitative method could be used for quantitative detection of two GM cotton events (GHB119 and T304-40) and Cry2Ae gene ingredient in cotton derived products. PMID:24884946

  9. Synthetic carbon precursor materials

    SciTech Connect

    Frame, B.J.

    1986-03-01

    Synthetic carbon precursor systems offer advantages over natural petroleum and coal-tar pitch precursors in that they can reproducibly provide a material with a known and uniform composition. They also permit controlled modifications of the derived carbon's properties through variations in the precursor's properties and processing conditions. Extensive research efforts at Oak Ridge have been directed toward the production and characterization of synthetic carbon precursors and the correlations that exist between carbon precursor properties and the properties of the ultimate carbon. This report describes how synthetic carbon precursors can be used to tailor and develop reproducible carbon structures for advanced materials applications. The potential and capability for performing carbon material development at Oak Ridge is also described.

  10. Polyimide Precursor Solid Residuum

    NASA Technical Reports Server (NTRS)

    Weiser, Erik S. (Inventor); St.Clair, Terry L. (Inventor); Echigo, Yoshiaki (Inventor); Kaneshiro, Hisayasu (Inventor)

    2001-01-01

    A polyimide precursor solid residuum is an admixture of an aromatic dianhydride or derivative thereof and an aromatic diamine or derivative thereof plus a complexing agent, which is complexed with the admixture by hydrogen bonding. The polyimide precursor solid residuum is effectively employed in the preparation of polyimide foam and the fabrication of polyimide foam structures.

  11. Simultaneous analysis method for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin in urine, using C18 poroshell column.

    PubMed

    Anilanmert, Beril; Çavuş, Fatma; Narin, Ibrahim; Cengiz, Salih; Sertler, Şefika; Özdemir, Ali Acar; Açikkol, Münevver

    2016-06-01

    Date-rape drugs have the potential to be used in drug-facilitated sexual assault, organ theft and property theft. Since they are colorless, tasteless and odorless, victims can drink without noticing, when added to the beverages. These drugs must be detected in time, before they are cleared up from the biofluids. A simultaneous extraction and determination method in urine for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin (an anticonvulsant and antiepileptic drug) with LC-MS/MS was developed for the first time with analytically acceptable recoveries and validated. A 4 steps liquid-liquid extraction was applied, using only 1.000mL urine. A new age commercial C18 poroshell column with high column efficiency was used for LC-MS/MS analysis with a fast isocratic elution as 5.5min. A new MS transition were introduced for barbital. 222.7>179.8 with the effect of acetonitrile. Recoveries (%) were between 80.98-99.27 for all analytes, except for GHB which was 71.46. LOD and LOQ values were found in the ranges of 0.59-49.50 and 9.20-80.80ngmL(-1) for all the analytes (except for GHB:3.44 and 6.00μgmL(-1)). HorRat values calculated (between 0.25-1.21), revealed that the inter-day and interanalist precisions (RSD%≤14.54%) acceptable. The simultaneous extraction and determination of these 8 analytes in urine is challenging because of the difficulty arising from the different chemical properties of some. Since the procedure can extract drugs from a wide range of polarity and pKa, it increases the window of detection. Group representatives from barbiturates, z-drugs, ketamine, phenytoin and polar acidic drugs (GHB) have been successfully analyzed in this study with low detection limits. The method is important from the point of determining the combined or single use of these drugs in crimes and finding out the reasons of deaths related to these drugs.

  12. Precursors to Lymphoproliferative Malignancies

    PubMed Central

    Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

    2013-01-01

    We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. PMID:23549397

  13. Earthquakes: hydrogeochemical precursors

    USGS Publications Warehouse

    Ingebritsen, Steven E.; Manga, Michael

    2014-01-01

    Earthquake prediction is a long-sought goal. Changes in groundwater chemistry before earthquakes in Iceland highlight a potential hydrogeochemical precursor, but such signals must be evaluated in the context of long-term, multiparametric data sets.

  14. A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen.

    PubMed

    Irwin, Richard D

    2006-01-01

    1,4-Butanediol is an industrial chemical used primarily as an intermediate in the manufacture of other organic chemicals. It has recently been associated with deaths, addiction and withdrawal related to its promotion and use as a dietary supplement. The rapid absorption and conversion of 1,4-butanediol to gamma-hydroxybutyric acid (GHB, or date rape drug) in animals and humans is well documented and is the basis for its abuse potential. A disposition and metabolism study conducted in F344 rats by the National Toxicology Program (NTP) confirmed the rapid conversion of 1-(14)C-1,4-butanediol to (14)CO2. Because of this, the toxicological profile of 1,4-butanediol resembles that of gamma-hydroxybutyric acid. Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. Although the function of gamma-hydroxybutyric acid in peripheral tissues is not known, the presence of specific high affinity receptors for gamma-hydroxybutyric acid suggests that it functions as a neuromodulator in the brain and neuronal tissue. Gamma-hydroxybutyric acid readily crosses the blood-brain barrier and elicits characteristic neuropharmacologic responses after oral, i.p., or i.v. administration. The same responses are observed after administration of 1,4-butanediol. The cyclic lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver in animals and humans, and produces pharmacological effects identical to those produced by 1,4-butanediol and gamma-hydroxybutyric acid. Gamma-butyrolactone was previously evaluated by the NTP in 14-day and 13-week prechronic toxicology studies and in 2-year chronic toxicology and carcinogenesis studies in F344 rats and B6C3F1 mice. No organ specific toxicity occurred. In the carcinogenesis studies there was an equivocal response in male mice based on a marginal increase in the incidence

  15. Enzymatic detection of γ-hydroxybutyrate using aldo-keto reductase 7A2.

    PubMed

    Bendinskas, Kestutis; Sattelberg, Patricia; Crossett, Daniel; Banyikwa, Andrew; Dempsey, Daniel; MacKenzie, James A

    2011-05-01

    Gamma-hydroxybutyrate (GHB) is a prescribed medication as well as a drug of abuse. Its detection in various matrices for in-field forensic scientists remains a challenge. We have developed an assay that uses aldo-keto reductase 7A2 (AKR7A2) for the specific determination of GHB in various drinks. AKR7A2 was purified using Ni-affinity chromatography. The Michaelis-Menten constant for the GHB oxidation reaction was 10 mM, and the minimum detection limit was 4 mM. Ethanol was not a substrate for AKR7A2. In a coupled reaction with NADP(+), phenazine methosulfate (PMS), and 2,6-dichlorophenolindophenol, various beverages (orange juice, milk, soda, and numerous alcoholic drinks) containing GHB turned from blue to light yellow. In a second coupled reaction where diaphorase replaced PMS, the presence of GHB also caused the expected change of color in various beers.

  16. In Vitro and In Vivo Evidence for Active Brain Uptake of the GHB Analog HOCPCA by the Monocarboxylate Transporter Subtype 1.

    PubMed

    Thiesen, Louise; Kehler, Jan; Clausen, Rasmus P; Frølund, Bente; Bundgaard, Christoffer; Wellendorph, Petrine

    2015-08-01

    γ-Hydroxybutyric acid (GHB) is a recreational drug, a clinically prescribed drug in narcolepsy and alcohol dependence, and an endogenous substance that binds to both high- and low-affinity sites in the brain. For studying the molecular mechanisms and the biologic role of the GHB high-affinity binding sites, ligands with high and specific affinity are essential. The conformationally restricted GHB analog HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) is one such compound. The objective of this study was to investigate the transport of HOCPCA across the blood-brain barrier in vitro and in vivo and to investigate the hypothesis that HOCPCA, like GHB, is a substrate for the monocarboxylate transporters (MCTs). For in vitro uptake studies, MCT1, -2, and -4 were recombinantly expressed in Xenopus laevis oocytes, and the previously reported radioligand [(3)H]HOCPCA was used as substrate. HOCPCA inhibited the uptake of the endogenous MCT substrate l-[(14)C]lactate, and [(3)H]HOCPCA was shown to act as substrate for MCT1 and 2 (Km values in the low- to mid-millimolar range). Introducing single-point amino acid mutations into positions essential for MCT function supported that HOCPCA binds to the endogenous substrate pocket of MCTs. MCT1-mediated brain entry of HOCPCA (10 mg/kg s.c.) was further confirmed in vivo in mice by coadministration of increasing doses of the MCT inhibitor AR-C141990 [(R)-5-(3-hydroxypyrrolidine-1-carbonyl)-1-isobutyl-3-methyl-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione], which inhibited brain penetration of HOCPCA in a dose-dependent manner (ID50 = 4.6 mg/kg). Overall, our study provides evidence that MCT1 is an important brain entry site for HOCPCA and qualifies for future in vivo studies with HOCPCA.

  17. The EM Earthquake Precursor

    NASA Astrophysics Data System (ADS)

    Jones, K. B., II; Saxton, P. T.

    2013-12-01

    Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After the 1989 Loma Prieta Earthquake, American earthquake investigators predetermined magnetometer use and a minimum earthquake magnitude necessary for EM detection. This action was set in motion, due to the extensive damage incurred and public outrage concerning earthquake forecasting; however, the magnetometers employed, grounded or buried, are completely subject to static and electric fields and have yet to correlate to an identifiable precursor. Secondly, there is neither a networked array for finding any epicentral locations, nor have there been any attempts to find even one. This methodology needs dismissal, because it is overly complicated, subject to continuous change, and provides no response time. As for the minimum magnitude threshold, which was set at M5, this is simply higher than what modern technological advances have gained. Detection can now be achieved at approximately M1, which greatly improves forecasting chances. A propagating precursor has now been detected in both the field and laboratory. Field antenna testing conducted outside the NE Texas town of Timpson in February, 2013, detected three strong EM sources along with numerous weaker signals. The antenna had mobility, and observations were noted for recurrence, duration, and frequency response. Next, two

  18. Identified EM Earthquake Precursors

    NASA Astrophysics Data System (ADS)

    Jones, Kenneth, II; Saxton, Patrick

    2014-05-01

    Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After a number of custom rock experiments, two hypotheses were formed which could answer the EM wave model. The first hypothesis concerned a sufficient and continuous electron movement either by surface or penetrative flow, and the second regarded a novel approach to radio transmission. Electron flow along fracture surfaces was determined to be inadequate in creating strong EM fields, because rock has a very high electrical resistance making it a high quality insulator. Penetrative flow could not be corroborated as well, because it was discovered that rock was absorbing and confining electrons to a very thin skin depth. Radio wave transmission and detection worked with every single test administered. This hypothesis was reviewed for propagating, long-wave generation with sufficient amplitude, and the capability of penetrating solid rock. Additionally, fracture spaces, either air or ion-filled, can facilitate this concept from great depths and allow for surficial detection. A few propagating precursor signals have been detected in the field occurring with associated phases using custom-built loop antennae. Field testing was conducted in Southern California from 2006-2011, and outside the NE Texas town of Timpson in February, 2013. The antennae have mobility and observations were noted for

  19. An interstellar precursor mission

    NASA Technical Reports Server (NTRS)

    Jaffe, L. D.; Ivie, C.; Lewis, J. C.; Lipes, R. G.; Norton, H. N.; Stearns, J. W.; Stimpson, L.; Weissman, P.

    1977-01-01

    A mission out of the planetary system, with launch about the year 2000, could provide valuable scientific data as well as test some of the technology for a later mission to another star. Primary scientific objectives for the precursor mission concern characteristics of the heliopause, the interstellar medium, stellar distances (by parallax measurements), low energy cosmic rays, interplanetary gas distribution, and mass of the solar system. Secondary objectives include investigation of Pluto. Candidate science instruments are suggested. Individual spacecraft systems for the mission were considered, technology requirements and problem areas noted, and a number of recommendations made for technology study and advanced development. The most critical technology needs include attainment of 50-yr spacecraft lifetime and development of a long-life NEP system.

  20. Generation of Nonlinear Vortex Precursors

    NASA Astrophysics Data System (ADS)

    Chen, Yue-Yue; Feng, Xun-Li; Liu, Chengpu

    2016-07-01

    We numerically study the propagation of a few-cycle pulse carrying orbital angular momentum (OAM) through a dense atomic system. Nonlinear precursors consisting of high-order vortex harmonics are generated in the transmitted field due to carrier effects associated with ultrafast Bloch oscillation. The nonlinear precursors survive to propagation effects and are well separated with the main pulse, which provides a straightforward way to measure precursors. By virtue of carrying high-order OAM, the obtained vortex precursors as information carriers have potential applications in optical information and communication fields where controllable loss, large information-carrying capacity, and high speed communication are required.

  1. Preparation of superconductor precursor powders

    DOEpatents

    Bhattacharya, Raghunath

    1998-01-01

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

  2. Determination of endogenous concentration of γ-hydroxybutyric acid (GHB) in hair through an ad hoc GC-MS analysis: A study on a wide population and influence of gender and age.

    PubMed

    Vaiano, Fabio; Serpelloni, Giovanni; Furlanetto, Sandra; Palumbo, Diego; Mari, Francesco; Fioravanti, Alessia; Bertol, Elisabetta

    2016-01-25

    γ-Hydroxybutyric acid (GHB) spread for recreational purposes or as "rape drug" represents a hard issue for forensic toxicologists due to its endogenous nature. It is clear that an actual and reliable discrimination between basal and exogenous levels is mandatory to achieve a correct evaluation of conscious/unconscious administration. This research aimed to study the GHB baseline in hair samples, collected from 150 volunteers, non-consumers of any drugs of abuse, in order to evaluate if a generic cut-off value could be accepted, also focusing on potential influences of gender and age. The analysis consisted of an overnight incubation with NaOH at 56 °C, liquid-liquid extraction with ethylacetate and trimethylsylil derivatization. Detection was carried out through gas chromatography-mass spectrometry in single ion monitoring (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in "blank" hair was estimated by the standard addition method. Concentration range was 0.279-2.839 ng/mg. In males, the average GHB levels were higher than in females (0.829 vs 0.596 ng/mg, respectively), especially in the first age category (<30 years, 1.008 vs 0.606 ng/mg, respectively). Age influences on GHB levels seemed to be different among the two sexes: in male population concentrations were higher <30 (1.008 ng/mg) and similar in the other age ranges (0.762 ng/mg, 30-50; 0.763 ng/mg, >50); in female, quite similar levels were registered throughout all the age categories (0.606 ng/mg, <30; 0.536 ng/mg, 30-50; 0.691 ng/mg, >50). Further study should be performed on GHB physiology in order to better understand these differences among ages and genders. Moreover, we demonstrated that for hair analysis a cut-off reference value is not strictly mandatory, underlining the great interpretative valence of segmental analysis.

  3. Precursor decay in several aluminas

    NASA Astrophysics Data System (ADS)

    Murray, N. H.; Bourne, N. K.; Rosenberg, Z.

    1996-05-01

    Plate impact experiments were performed on three ceramics with alumina content varying from 88 to 99.9% using a 50 mm single stage gas gun. Tiles of ceramic with thicknesses varying from 2 to 12 mm were impacted above their Hugoniot Elastic Limits (HELs) and the rate dependent strength was investigated by monitoring the variation in amplitude of the elastic precursor with propagation distance. Stress levels in the target were recorded using manganin stress transducers and a 1 GS s-1 storage oscilloscope. All grades of alumina were found to exhibit some elastic precursor decay indicating strain rate sensitivity.

  4. Preparation of superconductor precursor powders

    DOEpatents

    Bhattacharya, R.

    1998-08-04

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products. 7 figs.

  5. Preparation of superconductor precursor powders

    DOEpatents

    Bhattacharya, Raghunath; Blaugher, Richard D.

    1995-01-01

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals, such as nitrate salts of thallium, barium, calcium, and copper, which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of thallium in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

  6. PAGOSA Sample Problem. Elastic Precursor

    SciTech Connect

    Weseloh, Wayne N.; Clancy, Sean Patrick

    2016-02-03

    A PAGOSA simulation of a flyer plate impact which produces an elastic precursor wave is examined. The simulation is compared to an analytic theory for the Mie-Grüneisen equation of state and an elastic-perfectly-plastic strength model.

  7. Precursor polymer compositions comprising polybenzimidazole

    SciTech Connect

    Klaehn, John R.; Peterson, Eric S.; Orme, Christopher J.

    2015-07-14

    Stable, high performance polymer compositions including polybenzimidazole (PBI) and a melamine-formaldehyde polymer, such as methylated, poly(melamine-co-formaldehyde), for forming structures such as films, fibers and bulky structures. The polymer compositions may be formed by combining polybenzimidazole with the melamine-formaldehyde polymer to form a precursor. The polybenzimidazole may be reacted and/or intertwined with the melamine-formaldehyde polymer to form the polymer composition. For example, a stable, free-standing film having a thickness of, for example, between about 5 .mu.m and about 30 .mu.m may be formed from the polymer composition. Such films may be used as gas separation membranes and may be submerged into water for extended periods without crazing and cracking. The polymer composition may also be used as a coating on substrates, such as metal and ceramics, or may be used for spinning fibers. Precursors for forming such polymer compositions are also disclosed.

  8. Soluble Precursor Route to Polyanilines

    DTIC Science & Technology

    1993-01-01

    condensation were not successful, but further work produced polymer under the following conditions: Synthesis Diketone I (2.40 g, 10.0 mmol) in 10 mL...goal of producing a processible form of the conducting polymer polyaniline (PANI), the Phase I program concentrated on development of the synthesis of...extension of the original research to a Phase II effort. Diketone - Diamine Polycondensation Towards a Soluble PAni Precursor To achieve the

  9. Nucleation precursors in protein crystallization

    PubMed Central

    Vekilov, Peter G.; Vorontsova, Maria A.

    2014-01-01

    Protein crystal nucleation is a central problem in biological crystallography and other areas of science, technology and medicine. Recent studies have demonstrated that protein crystal nuclei form within crucial precursors. Here, methods of detection and characterization of the precursors are reviewed: dynamic light scattering, atomic force microscopy and Brownian microscopy. Data for several proteins provided by these methods have demonstrated that the nucleation precursors are clusters consisting of protein-dense liquid, which are metastable with respect to the host protein solution. The clusters are several hundred nanometres in size, the cluster population occupies from 10−7 to 10−3 of the solution volume, and their properties in solutions supersaturated with respect to crystals are similar to those in homogeneous, i.e. undersaturated, solutions. The clusters exist owing to the conformation flexibility of the protein molecules, leading to exposure of hydrophobic surfaces and enhanced intermolecular binding. These results indicate that protein conformational flexibility might be the mechanism behind the metastable mesoscopic clusters and crystal nucleation. Investigations of the cluster properties are still in their infancy. Results on direct imaging of cluster behaviors and characterization of cluster mechanisms with a variety of proteins will soon lead to major breakthroughs in protein biophysics. PMID:24598910

  10. Baclofen for narcolepsy with cataplexy: two cases

    PubMed Central

    Lee, Elliott Kyung; Douglass, Alan Bruce

    2015-01-01

    Narcolepsy is a disabling sleep disorder characterized by daytime hypersomnolence. Those with cataplexy have spells of muscle weakness precipitated by strong emotions, especially laughter or surprise. Cataplexy treatments include antidepressants or a GABA-B agonist, gamma hydroxybutyrate (GHB). GHB is the most effective treatment for cataplexy, but is expensive and can have significant side effects. A recent report of a murine model of narcolepsy-cataplexy suggests R-baclofen has potential efficacy against cataplexy. We report on two narcolepsy patients with multiple daily cataplexy episodes, one of whom had been effectively treated with GHB, but had to discontinue it for unrelated medical reasons. Both subsequently tried baclofen and experienced almost complete resolution of cataplexy. This report suggests baclofen can be an effective treatment for cataplexy in humans and warrants further study. PMID:26251634

  11. New Worlds Observer Precursor Mission

    NASA Astrophysics Data System (ADS)

    Lillie, C. F.; Lo, A. S.; Dailey, D.; Glassman, T. M.

    2007-06-01

    The New Worlds Observer architecture uses an external occulter to extinguish the on-axis light from a star and a separate telescope to collect the light from objects around that star, such as planets and debris disks. The separation of the starlight suppression capability from the photon collection capability makes the New Worlds Observer architecture very flexible. This paper describes NWO concepts ranging from low-cost precursor missions to Terrestrial Planet Finding (TPF) missions, and provides a path that extends beyond TPF to Planet-Imager and LifeFinder. Low cost precursor missions could be launched on a Minotaur using a small(~10 meter) occulter to work with a small(~0.5 m), telescope. Intermediate precursor missions could be accomplished by launching a larger occulter as a secondary payload to work with existing telescopes such as SOFIA or JWST. The former may allow direct detection of known giant planets, while the latter has the potential to discover Exo-Earths. A full TPF mission would consists of a large occulter working with a dedicated telescope; this can potentially find many terrestrial planets, as well as perform a host of ancillary astronomy investigations such as imaging debris disks and characterizing atmospheres of Jovian planets, as well as making general astrophysics observations. By utilizing the in space servicing capabilities that may be developed for the Exploration program, the lifetime of these occulters may be greatly extended by refueling and repair. In the future, larger occulters (>100 m) could be assembled on orbit. Thus, when coupled with a large telescope, the NWO architecture provides a path towards Lifefinder. NWO is a flexible architecture that allows scalability on all levels to suit the budget available for Exo-Planet Missions.

  12. Precursors of Short Gamma-Ray Bursts

    NASA Technical Reports Server (NTRS)

    Troja, E.; Rosswog, S.; Gehrels, N.

    2010-01-01

    We carried out a systematic search of precursors on the sample of short GRBs observed by Swift. We found that approx. 8-10% of short GRBs display such early episode of emission. One burst (GRB 090510) shows two precursor events, the former approx.13 s and the latter approx. 0.5 s before the GRB. We did not find any substantial difference between the precursor and the main GRB emission, and between short GRBs with and without precursors. We discuss possible mechanisms to reproduce the observed precursor emission within the scenario of compact object mergers. The implications of our results on quantum gravity constraints are also discussed.

  13. Annealing of aromatic polyimide precursors

    NASA Technical Reports Server (NTRS)

    Wakelyn, N. T.

    1975-01-01

    A study has been made of the thermal behavior of polyimide precursors: an isomeric pair of crystals of the complex formed by p-phenylenediamine with the separated isomers of the di-isopropyl ester of pyromellitic acid. Specimens of this material were isothermally annealed in the temperature range 120 C to 170 C for periods of time up to 1 week. Although this temperature range is well below that customarily used for imidizations, the working hypothesis was that it would be more likely that a polymer embodying at least part of the precursor structure could be formed if the molecular motion was minimized to that actually required for the formation of the imide linkage. The progress of the annealing was followed by: infrared spectroscopy, differential thermal analysis, powder X-ray diffraction, and thermal gravimetric analysis. Single crystal X-ray analysis of the meta monomer yields a structure of chains of alternating acid and base and suggests that this monomer is amenable to polymerization with a minimum of geometrical disruption.

  14. Molecular and polymeric ceramic precursors

    SciTech Connect

    Sneddon, L.G.

    1991-08-01

    The development of new methods for the production of complex materials is one of the most important problems in modern solid state chemistry and materials science. This project is attempting to apply the synthetic principles which have evolved inorganic and organometallic chemistry to the production of technologically important non-oxide ceramics, such as boron nitride, boron carbide and metal borides. Our recent work has now resulted in the production of new polymer systems, including poly(B-vinylborazine), polyvinylpentaborane and polyborazylene, that have proven to be high yield precursors to boron-based ceramic materials. Current work is now directed toward the synthesis of new types of molecular and polymeric boron-containing species and on exploration of the solid state properties of the ceramics that have been produced in these studies.

  15. Intermolecular Interactions between Eosin Y and Caffeine Using 1H-NMR Spectroscopy

    PubMed Central

    Okuom, Macduff O.; Wilson, Mark V.; Jackson, Abby; Holmes, Andrea E.

    2014-01-01

    DETECHIP has been used in testing analytes including caffeine, cocaine, and tetrahydrocannabinol (THC) from marijuana, as well as date rape and club drugs such as flunitrazepam, gamma-hydroxybutyric acid (GHB), and methamphetamine. This study investigates the intermolecular interaction between DETECHIP sensor eosin Y (DC1) and the analyte (caffeine) that is responsible for the fluorescence and color changes observed in the actual array. Using 1H-NMR, 1H-COSY, and 1H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed. PMID:25018772

  16. Radio HF precursors of Earthquakes

    NASA Astrophysics Data System (ADS)

    Ruzhin, Yu.; Nomicos, C.; Vallianatos, F.; Shpakovsky, V.

    The high frequency (HF) earthquake electromagnetic precursors (40-55MHz band) were recorded by the four electromagnetic stations a few days (hours) prior the event associated with earthquakes with magnitude more than 5.0 at Crete Island. These experiments were performed continuously during 1998-2002 and specific peculiarities are found. This is underhorizon epicenter position for main part of events under question. Another unusual result is that such HF preseismic radio noise-like signals are responsible for seaquakes too. We made conclusion about developing of some thunderstorm-like charged clouds activity in atmosphere before the seismic event. As result of our analysis and interpretation of the available data of continuous observations on a network of Crete island we should state here, that in an atmosphere above the sea on the eve of earthquake at heights of 0.1-10 km the spatially distributed spots of sporadic charged clouds are occurred and the conditions for the electrical discharges in an atmosphere are created which can serve a source of HF radio-emission registered by Crete network. The atmosphere theory relations are used to model a corresponding to an anomalous event emissions generation observed on the Crete. The supposed mechanism of preseismic electricity generation is the model of convection carrier started in an atmosphere. It is governed by the horizontal gradient of air temperature. The occurrence of electrical charges in a surface of the sea and transportation them further on heights up to 10 km in our model occurs due to sporadic energy injections that allocated within bottom of the sea as gases and heat. The dimensions of width and height govern the size of atmosphere convection cells in the earthquake preparation area. These dimensions of the sporadic spots are close to 3 km each as it is derived from shadow geometry and spectral fluctuations of HF signal. Based on experience of Crete HF precursors observation the method for satellite mapping

  17. Leading time domain seismic precursors

    NASA Astrophysics Data System (ADS)

    Boucouvalas, A. C.; Gkasios, M.; Keskebes, A.; Tselikas, N. T.

    2014-08-01

    The problem of predicting the occurrence of earthquakes is threefold. On one hand it is necessary to predict the date and magnitude of an earthquake, and on the other hand the location of the epicenter. In this work after a brief review of the state of earthquake prediction research, we report on a new leading time precursor for determining time onset of earthquake occurrence. We report the linking between earthquakes of the past with those which happen in the future via Fibonacci, Dual and Lucas numbers (FDL) numbers. We demonstrate it here with two example seed earthquakes at least 100 years old. Using this leading indicator method we can predict significant earthquake events >6.5R, with good accuracy approximately +- 1 day somewhere in the world. From a single seed we produce at least 100 trials simultaneously of which 50% are correct to +- 1day. The indicator is based on Fibonacci, Dual and Lucas numbers (FDL). This result hints that the log periodic FDL numbers are at the root of the understanding of the earthquake mechanism. The theory is based on the assumption that each occurred earthquake discontinuity can be thought of as a generating source of FDL time series. (The mechanism could well be linked to planetary orbits). When future dates are derived from clustering and convergence from previous strong earthquake dates at an FDL time distance, then we have a high probability for an earthquake to occur on that date. We set up a real time system which generates FDL time series from each previous significant earthquake (>7R) and we produce a year to year calendar of high probability earthquake dates. We have tested this over a number of years with considerable success. We have applied this technique for strong (>7R) earthquakes across the globe as well as on a restricted region such as the Greek geographic region where the magnitude is small (>4R-6.5R). In both cases the success of the method is impressive. It is our belief that supplementing this method with

  18. The Interrelationships of Mathematical Precursors in Kindergarten

    ERIC Educational Resources Information Center

    Cirino, Paul T.

    2011-01-01

    This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 kindergarteners via latent variable techniques, and the contribution of precursors…

  19. Method of texturing a superconductive oxide precursor

    DOEpatents

    DeMoranville, Kenneth L.; Li, Qi; Antaya, Peter D.; Christopherson, Craig J.; Riley, Jr., Gilbert N.; Seuntjens, Jeffrey M.

    1999-01-01

    A method of forming a textured superconductor wire includes constraining an elongated superconductor precursor between two constraining elongated members placed in contact therewith on opposite sides of the superconductor precursor, and passing the superconductor precursor with the two constraining members through flat rolls to form the textured superconductor wire. The method includes selecting desired cross-sectional shape and size constraining members to control the width of the formed superconductor wire. A textured superconductor wire formed by the method of the invention has regular-shaped, curved sides and is free of flashing. A rolling assembly for single-pass rolling of the elongated precursor superconductor includes two rolls, two constraining members, and a fixture for feeding the precursor superconductor and the constraining members between the rolls. In alternate embodiments of the invention, the rolls can have machined regions which will contact only the elongated constraining members and affect the lateral deformation and movement of those members during the rolling process.

  20. The interrelationships of mathematical precursors in kindergarten.

    PubMed

    Cirino, Paul T

    2011-04-01

    This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 kindergarteners via latent variable techniques, and the contribution of precursors from each domain was established for small sums addition. Results showed a five-factor structure for the quantity precursors, with the major distinction being between nonsymbolic and symbolic tasks. The overall model demonstrated good fit and strong predictive power (R(2)=55%) for addition number combinations. Linguistic and spatial attention domains showed indirect relationships with outcomes, with their effects mediated by symbolic quantity measures. These results have implications for the measurement of mathematical precursors and yield promise for predicting future math performance.

  1. LETTER: Toroidally asymmetric ELM precursors in TCV

    NASA Astrophysics Data System (ADS)

    Reimerdes, H.; Pochelon, A.; Suttrop, W.

    1998-03-01

    Coherent magnetic oscillations precede edge localized modes (ELMs) in TCV. The precursor has been detected prior to ELMs considered to be of type III and others previously referred to as TCV large ELMs. This permits the identification of both as type III ELMs according to the usual classification scheme. The strong localization of these precursors on the bad curvature side of the plasma and their medium toroidal mode numbers indicate their ballooning character. Unlike conventional MHD modes, these modes start toroidally localized and grow in amplitude and toroidal extent. When the precursor encompasses the whole toroidal circumference, the increased transport phase, as indicated by the characteristic Dα spike, begins.

  2. Synthesis and structures of metal chalcogenide precursors

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius F.; Duraj, Stan A.; Eckles, William E.; Andras, Maria T.

    1990-01-01

    The reactivity of early transition metal sandwich complexes with sulfur-rich molecules such as dithiocarboxylic acids was studied. Researchers recently initiated work on precursors to CuInSe2 and related chalcopyrite semiconductors. Th every high radiation tolerance and the high absorption coefficient of CuInSe2 makes this material extremely attractive for lightweight space solar cells. Their general approach in early transition metal chemistry, the reaction of low-valent metal complexes or metal powders with sulfur and selenium rich compounds, was extended to the synthesis of chalcopyrite precursors. Here, the researchers describe synthesis, structures, and and routes to single molecule precursors to metal chalcogenides.

  3. Progress in molecular precursors for electronic materials

    SciTech Connect

    Buhro, W.E.

    1996-09-01

    Molecular-precursor chemistry provides an essential underpinning to all electronic-materials technologies, including photovoltaics and related areas of direct interest to the DOE. Materials synthesis and processing is a rapidly developing field in which advances in molecular precursors are playing a major role. This article surveys selected recent research examples that define the exciting current directions in molecular-precursor science. These directions include growth of increasingly complex structures and stoichiometries, surface-selective growth, kinetic growth of metastable materials, growth of size-controlled quantum dots and quantum-dot arrays, and growth at progressively lower temperatures. Continued progress in molecular-precursor chemistry will afford precise control over the crystal structures, nanostructures, and microstructures of electronic materials.

  4. Biochemical Removal of HAP Precursors From Coal

    SciTech Connect

    Olson, G.; Tucker, L.; Richards, J.

    1997-07-01

    This project addresses DOE`s interest in advanced concepts for controlling emissions of air toxics from coal-fired utility boilers. We are determining the feasibility of developing a biochemical process for the precombustion removal of substantial percentages of 13 inorganic hazardous air pollutant (HAP) precursors from coal. These HAP precursors are Sb, As, Be, Cd, Cr, Cl, Co, F, Pb, Hg, Mn, Ni, and Se. Although rapid physical coal cleaning is done routinely in preparation plants, biochemical processes for removal of HAP precursors from coal potentially offer advantages of deeper cleaning, more specificity, and less coal loss. Compared to chemical processes for coal cleaning, biochemical processes potentially offer lower costs and milder process conditions. Pyrite oxidizing bacteria, most notably Thiobacillusferrooxidans, are being evaluated in this project for their ability to remove HAP precursors from U.S. coals.

  5. Explorations Precursor Robotic Missions (xPRM)

    NASA Video Gallery

    Jay Jenkins delivers a presentation from the Exploration Precursor Robotic Missions (xPRM) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX. The purpose...

  6. Hydridosiloxanes as precursors to ceramic products

    DOEpatents

    Blum, Y.D.; Johnson, S.M.; Gusman, M.I.

    1997-06-03

    A method is provided for preparing ceramic precursors from hydridosiloxane starting materials and then pyrolyzing these precursors to give rise to silicious ceramic materials. Si-H bonds present in the hydridosiloxane starting materials are catalytically activated, and the activated hydrogen atoms may then be replaced with nonhydrogen substituents. These preceramic materials are pyrolyzed in a selected atmosphere to give the desired ceramic product. Ceramic products which may be prepared by this technique include silica, silicon oxynitride, silicon carbide, metal silicates, and mullite.

  7. Psychosis in the Context of Sodium Oxybate Therapy

    PubMed Central

    Langford, Jody; Gross, William L.

    2011-01-01

    Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medication, as well as withdrawal symptoms, even at clinical doses. Citation: Langford J; Gross WL. Psychosis in the context of sodium oxybate therapy. J Clin Sleep Med 2011;7(6):665-666. PMID:22171207

  8. Nozzle designs with pitch precursor ablatives

    NASA Technical Reports Server (NTRS)

    Blevins, H. R.; Bedard, R. J.

    1976-01-01

    Recent developments in carbon phenolic ablatives for solid rocket motor nozzles have yielded a pitch precursor carbon fiber offering significant raw material availability and cost saving advantages as compared to conventional rayon precursor material. This paper discusses the results of an experimental program conducted to assess the thermal performance and characterize the thermal properties of pitch precursor carbon phenolic ablatives. The end result of this program is the complete thermal characterization of pitch fabric, pitch mat, hybrid pitch/rayon fabric and pitch mat molding compound. With these properties determined an analytic capability now exists for predicting the thermal performance of these materials in rocket nozzle liner applications. Further planned efforts to verify material performance and analytical prediction procedures through actual rocket motor firings are also discussed.

  9. Sequestration and Transport of Lignin Monomeric Precursors

    SciTech Connect

    Liu, C.J.; Miao, Y.-C.; Zhang, K.-W.

    2011-01-18

    Lignin is the second most abundant terrestrial biopolymer after cellulose. It is essential for the viability of vascular plants. Lignin precursors, the monolignols, are synthesized within the cytosol of the cell. Thereafter, these monomeric precursors are exported into the cell wall, where they are polymerized and integrated into the wall matrix. Accordingly, transport of monolignols across cell membranes is a critical step affecting deposition of lignin in the secondarily thickened cell wall. While the biosynthesis of monolignols is relatively well understood, our knowledge of sequestration and transport of these monomers is sketchy. In this article, we review different hypotheses on monolignol transport and summarize the recent progresses toward the understanding of the molecular mechanisms underlying monolignol sequestration and transport across membranes. Deciphering molecular mechanisms for lignin precursor transport will support a better biotechnological solution to manipulate plant lignification for more efficient agricultural and industrial applications of cell wall biomass.

  10. Precursors prior to type IIn supernova explosions are common: Precursor rates, properties, and correlations

    SciTech Connect

    Ofek, Eran O.; Steinbok, Aviram; Arcavi, Iair; Gal-Yam, Avishay; Tal, David; Ben-Ami, Sagi; Yaron, Ofer; Sullivan, Mark; Shaviv, Nir J.; Kulkarni, Shrinivas R.; Nugent, Peter E.; Kasliwal, Mansi M.; Cenko, S. Bradley; Silverman, Jeffrey M.

    2014-07-10

    There is a growing number of Type IIn supernovae (SNe) which present an outburst prior to their presumably final explosion. These precursors may affect the SN display, and are likely related to poorly charted phenomena in the final stages of stellar evolution. By coadding Palomar Transient Factory (PTF) images taken prior to the explosion, here we present a search for precursors in a sample of 16 Type IIn SNe. We find five SNe IIn that likely have at least one possible precursor event (PTF 10bjb, SN 2010mc, PTF 10weh, SN 2011ht, and PTF 12cxj), three of which are reported here for the first time. For each SN we calculate the control time. We find that precursor events among SNe IIn are common: at the one-sided 99% confidence level, >50% of SNe IIn have at least one pre-explosion outburst that is brighter than 3 × 10{sup 7} L{sub ☉} taking place up to 1/3 yr prior to the SN explosion. The average rate of such precursor events during the year prior to the SN explosion is likely ≳ 1 yr{sup –1}, and fainter precursors are possibly even more common. Ignoring the two weakest precursors in our sample, the precursors rate we find is still on the order of one per year. We also find possible correlations between the integrated luminosity of the precursor and the SN total radiated energy, peak luminosity, and rise time. These correlations are expected if the precursors are mass-ejection events, and the early-time light curve of these SNe is powered by interaction of the SN shock and ejecta with optically thick circumstellar material.

  11. Polymeric precursors for fibers and matrices

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1992-01-01

    Candidate polymeric precursors for ceramic fiber and matrix processing are discussed, with a view to the advantages and disadvantages of this approach relative to existing alternatives. The properties of ceramic products thus derived are noted to strongly depend on the molecular weight and structure of the starting polymer; in particular, the ceramic's composition and morphology are dependent on the character and extent of crosslinking, as well as on the path of pyrolysis. While large and complex structural ceramic components may ultimately be obtainable by these means, the polymer-precursor method is still in its developmental infancy.

  12. Nonlinear magnetohydrodynamics of edge localized mode precursors

    NASA Astrophysics Data System (ADS)

    Guo, Z. B.; Wang, Lu; Wang, X. G.

    2015-02-01

    A possible origin of edge-localized-mode (ELM) precursors based on nonlinear ideal peeling-ballooning mode is reported. Via nonlinear variational principle, a nonlinear evolution equation of the radial displacement is derived and solved, analytically. Besides an explosive growth in the initial nonlinear phase, it is found that the local displacement evolves into an oscillating state in the developed nonlinear phase. The nonlinear frequency of the ELM precursors scales as ωpr e˜x1 /3ξ̂ψ,i n 2 /3n , with x position in radial direction, ξ̂ ψ,i n strength of initial perturbation, and n toroidal mode number.

  13. Biochemical Removal of HAP Precursors from Coal

    SciTech Connect

    Olson, Gregory J

    1997-05-12

    Column biooxidation tests with Kentucky coal confirmed results of earlier shake flask tests showing significant removal from the coal of arsenic, selenium, cobalt, manganese, nickel and cadmium. Rates of pyrite biooxidation in Kentucky coal were only slightly more than half the rates found previously for Indiana and Pittsburgh coals. Removal of pyrite from Pittsburgh coal by ferric ion oxidation slows markedly as ferrous ions accumulate in solution, requiring maintenance of high redox potentials in processes designed for removal of pyrite and hazardous air pollutant (HAP) precursors by circulation of ferric solutions through coal. The pyrite oxidation rates obtained in these tests were used by Unifield Engineering to support the conceptual designs for alternative pyrite and HAP precursor bioleaching processes for the phase 2 pilot plant. Thermophilic microorganisms were tested to determine if mercury could be mobilized from coal under elevated growth temperatures. There was no evidence for mercury removal from coal under these conditions. However, the activity of the organisms may have liberated mercury physically. It is also possible that the organisms dissolved mercury and it readsorbed to the clay preferentially. Both of these possibilities are undergoing further testing. The Idaho National Engineering and Environmental Laboratory's (INEEL) slurry column reactor was operated and several batches of feed coal, product coal, waste solids and leach solutions were submitted to LBL for HAP precursor analysis. Results to date indicate significant removal of mercury, arsenic and other HAP precursors in the combined physical-biological process.

  14. Janus microgels produced from functional precursor polymers.

    PubMed

    Seiffert, Sebastian; Romanowsky, Mark B; Weitz, David A

    2010-09-21

    Micrometer-sized Janus particles of many kinds can be formed using droplet microfluidics, but in existing methods, the microfluidic templating is strongly coupled to the material synthesis, since droplet solidification occurs through rapid polymerization right after droplet formation. This circumstance limits independent control of the material properties and the morphology of the resultant particles. In this paper, we demonstrate a microfluidic technique to produce functional Janus microgels from prefabricated, cross-linkable precursor polymers. This approach separates the polymer synthesis from the particle gelation, thus allowing the microfluidic droplet templating and the functionalization of the matrix polymer to be performed and controlled in two independent steps. We use microfluidic devices to emulsify semidilute solutions of cross-linkable, chemically modified or unmodified poly(N-isopropylacrylamide) precursors and solidify the drops via polymer-analogous gelation. The resultant microgel particles exhibit two distinguishable halves which contain most of the modified precursors, and the unmodified matrix polymer separates these materials. The spatial distribution of the modified precursors across the particles can be controlled by the flow rates during the microfluidic experiments. We also form hollow microcapsules with two different sides (Janus shells) using double emulsion droplets as templates, and we produce Janus microgels that are loaded with a ferromagnetic additive which allows remote actuation of the microgels.

  15. Profiling Identifies Precursor Suspects: Notch Family Again!

    PubMed Central

    Breunig, Joshua J.; Rakic, Pasko

    2011-01-01

    Newborn neurons in the adult dentate gyrus pass through several distinct precursor and progenitor classes prior to differentiation. In this issue of Cell Stem Cell, Lugert et al. (2010) characterized their strikingly different proliferative behaviors after neurogenic stimuli or aging. PMID:20452310

  16. Superconductor precursor mixtures made by precipitation method

    DOEpatents

    Bunker, Bruce C.; Lamppa, Diana L.; Voigt, James A.

    1989-01-01

    Method and apparatus for preparing highly pure homogeneous precursor powder mixtures for metal oxide superconductive ceramics. The mixes are prepared by instantaneous precipitation from stoichiometric solutions of metal salts such as nitrates at controlled pH's within the 9 to 12 range, by addition of solutions of non-complexing pyrolyzable cations, such as alkyammonium and carbonate ions.

  17. Sol-gel precursors and products thereof

    DOEpatents

    Warren, Scott C.; DiSalvo, Jr., Francis J.; Weisner, Ulrich B.

    2017-02-14

    The present invention provides a generalizable single-source sol-gel precursor capable of introducing a wide range of functionalities to metal oxides such as silica. The sol-gel precursor facilitates a one-molecule, one-step approach to the synthesis of metal-silica hybrids with combinations of biological, catalytic, magnetic, and optical functionalities. The single-source precursor also provides a flexible route for simultaneously incorporating functional species of many different types. The ligands employed for functionalizing the metal oxides are derived from a library of amino acids, hydroxy acids, or peptides and a silicon alkoxide, allowing many biological functionalities to be built into silica hybrids. The ligands can coordinate with a wide range of metals via a carboxylic acid, thereby allowing direct incorporation of inorganic functionalities from across the periodic table. Using the single-source precursor a wide range of functionalized nanostructures such as monolith structures, mesostructures, multiple metal gradient mesostructures and Stober-type nanoparticles can be synthesized. ##STR00001##

  18. Detection of Chemical Precursors of Explosives

    NASA Technical Reports Server (NTRS)

    Li, Jing

    2012-01-01

    Certain selected chemicals associated with terrorist activities are too unstable to be prepared in final form. These chemicals are often prepared as precursor components, to be combined at a time immediately preceding the detonation. One example is a liquid explosive, which usually requires an oxidizer, an energy source, and a chemical or physical mechanism to combine the other components. Detection of the oxidizer (e.g. H2O2) or the energy source (e.g., nitromethane) is often possible, but must be performed in a short time interval (e.g., 5 15 seconds) and in an environment with a very small concentration (e.g.,1 100 ppm), because the target chemical(s) is carried in a sealed container. These needs are met by this invention, which provides a system and associated method for detecting one or more chemical precursors (components) of a multi-component explosive compound. Different carbon nanotubes (CNTs) are loaded (by doping, impregnation, coating, or other functionalization process) for detecting of different chemical substances that are the chemical precursors, respectively, if these precursors are present in a gas to which the CNTs are exposed. After exposure to the gas, a measured electrical parameter (e.g. voltage or current that correlate to impedance, conductivity, capacitance, inductance, etc.) changes with time and concentration in a predictable manner if a selected chemical precursor is present, and will approach an asymptotic value promptly after exposure to the precursor. The measured voltage or current are compared with one or more sequences of their reference values for one or more known target precursor molecules, and a most probable concentration value is estimated for each one, two, or more target molecules. An error value is computed, based on differences of voltage or current for the measured and reference values, using the most probable concentration values. Where the error value is less than a threshold, the system concludes that the target

  19. Treatment of disinfection by-product precursors.

    PubMed

    Bond, T; Goslan, E H; Parsons, S A; Jefferson, B

    2011-01-01

    Formation of harmful disinfection by-products (DBPs), of which trihalomethanes (THMs) and haloacetic acids (HAAs) are the major groups, can be controlled by removal of natural organic matter (NOM) before disinfection. In the literature, removal of precursors is variable, even with the same treatment. The treatment of DBP precursors and NOM was examined with the intention of outlining precursor removal strategies for various water types. Freundlich adsorption parameters and hydroxyl rate constants were collated from the literature to link treatability by activated carbon and advanced oxidation processes (AOPs), respectively, to physico-chemical properties. Whereas hydroxyl rate constants did not correlate meaningfully with any property, a moderate correlation was found between Freundlich parameters and log K(ow), indicating activated carbon will preferentially adsorb hydrophobic NOM. Humic components of NOM are effectively removed by coagulation, and, where they are the principal precursor source, coagulation may be sufficient to control DBPs. Where humic species remaining post-coagulation retain significant DBP formation potential (DBPFP), activated carbon is deemed a suitable process selection. Anion exchange is an effective treatment for transphilic species, known for high carboxylic acid functionality, and consequently is recommended for carboxylic acid precursors. Amino acids have been linked to HAA formation and are important constituents of algal organic matter. Amino acids are predicted to be effectively removed by biotreatment and nanofiltration. Carbohydrates have been found to reach 50% of NOM in river waters. If the carbohydrates were to pose a barrier to successful DBP control, additional treatment stages such as nanofiltration are likely to be required to reduce their occurrence.

  20. Boron nitride fibers from polymer precursors

    SciTech Connect

    Wade, B.E.

    1992-12-31

    Conversion of polymer precursors to high performance boron nitride fibers as explored through a fundamental study of the mutually dependent chemical, morphological, and processing requirements in precursor polymer synthesis, formation of continuous precursor fibers, and finally thermochemical conversion to oriented boron nitride fibers. Polyborate and polyborazylene precursors were investigated. method of incorporating polyborazine in polyborate were also explored in order to stabilize the shape of polyborate fibers and to help initiate an orientable boron nitride structure. Polyborazylene, a polyborazine of fused borazine polycyclic structures was chosen for study as a precursor for boron nitride fibers because of the closeness of its structure to that of the desired turbostratic boron nitride. Both poly(ethylene oxide) and poly(methyl methacrylate) were found to be compatible with the monomer, borazine, and polyborazylenesolutions with monoglyme. They could be used to build the viscosity of solutions. However, fibers that were hand-drawn from these solutions were very sticky and quickly hydrolyzed in room atmosphere. Conversion of polyborazylene to oriented boron nitride fibers was not realized. Processable polyborates were produced by polycondensation of trimethoxyboroxine and boric acid and also by disproportionation or trimethyoxyboraxine. It was shown that the rheological characteristics of the polyborate formed could be controlled by an appropriate combination of the conversion of the monomer to polymer and the addition of a linear organic polymer as a rheological aid. Poly(methyl methacrylate) was found to be a suitable rheological aid, with a decomposition temperature that is high enough to facilitate its incorporation in the polymerizing system and low energy to be fugitive during thermochemical conversion of the polyborate to boron nitride.

  1. Crystallization trends of precursor pyroxene in ordinary chondrites: Implications for igneous origin of precursor

    NASA Technical Reports Server (NTRS)

    Fujita, T.; Kitamura, M.

    1994-01-01

    Various observations suggest that the precursor of the fine fragments and the relict pyroxene was formed by an igneous process in a grandparent body of the chondrite. Furthermore, the fact that the precursors appear as fragments in the matrix as well as relicts in the chondrule suggests a shock origin for the chondrite by collision of two or more bodies, which had already to some extent undergone igneous differentiation.

  2. Topographical and functional properties of precursors to severe problem behavior.

    PubMed

    Fahmie, Tara A; Iwata, Brian A

    2011-01-01

    A literature search identified 17 articles reporting data on 34 subjects who engaged in precursors to severe problem behavior, which we examined to identify topographical and functional characteristics. Unintelligible vocalization was the most common precursor to aggression (27%) and property destruction (29%), whereas self- or nondirected movement was the most common precursor to SIB (32%). Unintelligible vocalization and object-directed movement were the most common precursors to behavior maintained by social-positive reinforcement (27% each), and unintelligible vocalization was the most common precursor to behavior maintained by social-negative reinforcement (29%). Only one precursor was reported for behavior maintained by automatic reinforcement.

  3. Electromagnetic Whistler Precursors at Supercritical Interplanetary Shocks

    NASA Technical Reports Server (NTRS)

    Wilson, L. B., III

    2012-01-01

    We present observations of electromagnetic precursor waves, identified as whistler mode waves, at supercritical interplanetary shocks using the Wind search coil magnetometer. The precursors propagate obliquely with respect to the local magnetic field, shock normal vector, solar wind velocity, and they are not phase standing structures. All are right-hand polarized with respect to the magnetic field (spacecraft frame), and all but one are right-hand polarized with respect to the shock normal vector in the normal incidence frame. Particle distributions show signatures of specularly reflected gyrating ions, which may be a source of free energy for the observed modes. In one event, we simultaneously observe perpendicular ion heating and parallel electron acceleration, consistent with wave heating/acceleration due to these waves.

  4. Nonlinear magnetohydrodynamics of edge localized mode precursors

    SciTech Connect

    Guo, Z. B.; Wang, Lu; Wang, X. G.

    2015-02-15

    A possible origin of edge-localized-mode (ELM) precursors based on nonlinear ideal peeling-ballooning mode is reported. Via nonlinear variational principle, a nonlinear evolution equation of the radial displacement is derived and solved, analytically. Besides an explosive growth in the initial nonlinear phase, it is found that the local displacement evolves into an oscillating state in the developed nonlinear phase. The nonlinear frequency of the ELM precursors scales as ω{sub pre}∼x{sup 1/3}ξ{sup ^}{sub ψ,in}{sup 2/3}n, with x position in radial direction, ξ{sup ^}{sub ψ,in} strength of initial perturbation, and n toroidal mode number.

  5. [Presentation of the Lunar Precursor Robotics Program

    NASA Technical Reports Server (NTRS)

    Lavoie, Anthony R.

    2008-01-01

    The Lunar Precursor Robotics Program (LPRP) is the host program for the Exploration Systems Mission Directorate's (ESMD) lunar robotic precursor missions to the Moon. The program includes two missions, the Lunar Reconnaissance Orbiter (LRO), and the Lunar CRater Observation and Sensing Satellite (LCROSS). Both missions will provide the required lunar information to support development and operations of those systems required for Human lunar return. LPRP is developing a lunar mapping plan, Called the Lunar Mapping and Modeling Project, to create the capability to archive and present all data from LRO, LCROSS, historical lunar missions, and international lunar missions for future mission planning and operations. LPRP is also developing its educational and public outreach activities for the Vision for Space Exploration's first missions. LPRP is working closely with the Science Mission Directorate as their lunar activities come into focus.

  6. User support for the Columbus precursor missions

    NASA Astrophysics Data System (ADS)

    Mirra, C.; Andersen, T. A. E.; Blume, H. T.; Brouwer, M. P. A. M.; Dangelo, L.; Duwe, H.; Eilersen, N.; Gaida, M.; Herten, M.; Iversen, T.-H.

    1992-07-01

    Based on the user Suport Organization (USO) definition concept, means by which user support for the precursor missions could be implemented are described. A survey of the facilities to be included in the Spacelab E1 and the Eureca 2 missions was performed. An overview of the national user support activities in Europe is given. It is assumed that this infrastructure can be applied for precursor mission support, as well. On the basis of the results of these two surveys, an exercise was executed to map the various support functions to be performed by the available utilization centers. In this work, the Facility Responsible Center and Experiment Support Center status was assigned to various centers. The results of the mapping exercise are presented.

  7. Chapter 14. Biosynthesis of nonribosomal peptide precursors.

    PubMed

    Wilkinson, Barrie; Micklefield, Jason

    2009-01-01

    Nonribosomal peptides are natural products typically of bacterial and fungal origin. These highly complex molecules display a broad spectrum of biological activities, and have been exploited for the development of immunosuppressant, antibiotic, anticancer, and other therapeutic agents. The nonribosomal peptides are assembled by nonribosomal peptide synthetase (NRPS) enzymes comprising repeating modules that are responsible for the sequential selection, activation, and condensation of precursor amino acids. In addition to this, fatty acids, alpha-keto acids and alpha-hydroxy acids, as well as polyketide derived units, can also be utilized by NRPS assembly lines. Final tailoring-steps, including glycosylation and prenylation, serve to further decorate the nonribosomal peptides produced. The wide range of experimental methods that are employed in the elucidation of nonribosomal peptide precursor biosynthesis will be discussed, with particularly emphasis on genomics based approaches which have become wide spread over the last 5 years.

  8. Precursors to radiopharmaceutical agents for tissue imaging

    DOEpatents

    Srivastava, Prem C.; Knapp, Jr., Furn F.

    1988-01-01

    A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

  9. Precursors to Rapid Elevations in Intracranial Pressure

    DTIC Science & Technology

    2007-11-02

    difference between the systemic arterial blood pressure and the intracranial pressure , CPP = ABP − ICP. 2Ischemia is a decrease in blood supply...and the average arterial blood pressure , µABP, were consistently higher. Our results seem to be inconsistent with the observations of previous studies...1 PRECURSORS TO RAPID ELEVATIONS IN INTRACRANIAL PRESSURE James McNames1, Cristina Crespo1, Mateo Aboy1, Miles Ellenby2, Susanna Lai2, Robert

  10. Calculations of precursor propagation in dispersive dielectrics.

    SciTech Connect

    Bacon, Larry Donald

    2003-08-01

    The present study is a numerical investigation of the propagation of electromagnetic transients in dispersive media. It considers propagation in water using Debye and composite Rocard-Powles-Lorentz models for the complex permittivity. The study addresses this question: For practical transmitted spectra, does precursor propagation provide any features that can be used to advantage over conventional signal propagation in models of dispersive media of interest? A companion experimental study is currently in progress that will attempt to measure the effects studied here.

  11. Generalized precursor pattern discovery for biomedical signals.

    PubMed

    Lan, Mars; Ghasemzadeh, Hassan; Sarrafzadeh, Majid

    2012-01-01

    With the advent of low-cost, high-fidelity, and long lasting sensors in recent years, it has become possible to acquire biomedical signals cheaply and remotely over a prolonged period of time. Oftentimes different types of sensors are deployed in the hope of capturing precursor patterns that are highly correlated to a particular clinical episode, such as seizure, congestive heart failure etc. While there have been several studies that successfully identify patterns as reliable precursors for specific medical conditions, most of them require domain-specific knowledge and expertise. The developed algorithms are also unlikely to be applicable to other medical conditions. In this paper we present a generalized algorithm that discovers potential precursor patterns without prior knowledge or domain expertise. The algorithm makes use of wavelet transform and information theory to extract generic features, and it is also classifier agnostic. Based on experiment results using three distinct datasets collected from real-world patients, our algorithm has attained performance comparable to those obtained from previous studies that rely heavily on domain-expert knowledge. Furthermore, the algorithm also discovers non-trivial knowledge in the process.

  12. Scalar model for frictional precursors dynamics

    PubMed Central

    Taloni, Alessandro; Benassi, Andrea; Sandfeld, Stefan; Zapperi, Stefano

    2015-01-01

    Recent experiments indicate that frictional sliding occurs by nucleation of detachment fronts at the contact interface that may appear well before the onset of global sliding. This intriguing precursory activity is not accounted for by traditional friction theories but is extremely important for friction dominated geophysical phenomena as earthquakes, landslides or avalanches. Here we simulate the onset of slip of a three dimensional elastic body resting on a surface and show that experimentally observed frictional precursors depend in a complex non-universal way on the sample geometry and loading conditions. Our model satisfies Archard's law and Amontons' first and second laws, reproducing with remarkable precision the real contact area dynamics, the precursors' envelope dynamics prior to sliding, and the normal and shear internal stress distributions close to the interfacial surface. Moreover, it allows to assess which features can be attributed to the elastic equilibrium, and which are attributed to the out-of-equilibrium dynamics, suggesting that precursory activity is an intrinsically quasi-static physical process. A direct calculation of the evolution of the Coulomb stress before and during precursors nucleation shows large variations across the sample, explaining why earthquake forecasting methods based only on accumulated slip and Coulomb stress monitoring are often ineffective. PMID:25640079

  13. Formulating Precursors for Coating Metals and Ceramics

    NASA Technical Reports Server (NTRS)

    Morales, Wilfredo; Gatica, Jorge E.; Reye, John T.

    2005-01-01

    A protocol has been devised for formulating low-vapor-pressure precursors for protective and conversion coatings on metallic and ceramic substrates. The ingredients of a precursor to which the protocol applies include additives with phosphate esters, or aryl phosphate esters in solution. Additives can include iron, chromium, and/or other transition metals. Alternative or additional additives can include magnesium compounds to facilitate growth of films on substrates that do not contain magnesium. Formulation of a precursor begins with mixing of the ingredients into a high-vapor-pressure solvent to form a homogeneous solution. Then the solvent is extracted from the solution by evaporation - aided, if necessary, by vacuum and/or slight heating. The solvent is deemed to be completely extracted when the viscosity of the remaining solution closely resembles the viscosity of the phosphate ester or aryl phosphate ester. In addition, satisfactory removal of the solvent can be verified by means of a differential scanning calorimetry essay: the absence of endothermic processes for temperatures below 150 C would indicate that the residual solvent has been eliminated from the solution beyond a detectable dilution level.

  14. Precursor lesions of invasive breast cancer.

    PubMed

    Schreer, Ingrid; Lüttges, Jutta

    2005-04-01

    The increasing application of mammography, mainly in screening programs for the early detection of breast cancer, and the high technical standard of imaging has resulted in the detection of clinically occult breast tumors. Considering that only diagnosis at an early stage will be able to change the prognosis of breast cancer, this diagnostic challenge appears to be the most exciting field in both breast imaging and breast pathology. Especially the precursor lesions need to be diagnosed and defined precisely to understand their prognostic significance. In imaging, the morphologic appearance of precursor lesions is usually neither typical nor pathognomonic. They have to be assessed histologically using percutaneous interventions. Recent molecular studies have demonstrated various genetic alterations in the ductal epithelium, with the earliest onset in atypical ductal hyperplasia. The recent WHO classification, which is based on molecular data and histopathological features, attempts to define in particular the precursor lesions and low grade intraductal carcinomas. The clinical importance of the various grades has to be assessed. Intimate cooperation between diagnostic radiologist and pathologist is essential.

  15. Characteristics of ELM precursors on NSTX

    NASA Astrophysics Data System (ADS)

    Ridha, Philipp; Menard, Jonathan; Stutman, Dan

    2005-10-01

    The precursor characteristics of Edge Localized Modes (ELMs) on NSTX were analyzed with Mirnov and USXR diagnostics in terms of toroidal mode number, growth rate, oscillation frequency, growth times before crash, and edge localization. Mode identification is especially difficult for most ELMs studied, as the precursor growth rates are often comparable to the oscillation period. Details of the mode identification process will be described. The Mirnov diagnostic does not tell whether the ELM is edge localized or not, thus the USXR array was used to discriminate between the edge and core plasma using an analysis of the X-ray emission with different metallic filters (Ti 0.4μm - E > 100eV, Be 10μm - E > 500eV, Be 100 μm - E > 1.2keV). Using the titanium filter, a strong correlation between Mirnov and USXR data during an ELM crash was observed. Analysis of the USXR data using a constrained tomographic inversion shows relative USXR fluctuation amplitudes from ELM precursors in the range of 1% to 5%. This analysis combined with an edge displacement model provides an estimate of the transient boundary displacements for typical ELMs of < 5 mm.

  16. Scalar model for frictional precursors dynamics.

    PubMed

    Taloni, Alessandro; Benassi, Andrea; Sandfeld, Stefan; Zapperi, Stefano

    2015-02-02

    Recent experiments indicate that frictional sliding occurs by nucleation of detachment fronts at the contact interface that may appear well before the onset of global sliding. This intriguing precursory activity is not accounted for by traditional friction theories but is extremely important for friction dominated geophysical phenomena as earthquakes, landslides or avalanches. Here we simulate the onset of slip of a three dimensional elastic body resting on a surface and show that experimentally observed frictional precursors depend in a complex non-universal way on the sample geometry and loading conditions. Our model satisfies Archard's law and Amontons' first and second laws, reproducing with remarkable precision the real contact area dynamics, the precursors' envelope dynamics prior to sliding, and the normal and shear internal stress distributions close to the interfacial surface. Moreover, it allows to assess which features can be attributed to the elastic equilibrium, and which are attributed to the out-of-equilibrium dynamics, suggesting that precursory activity is an intrinsically quasi-static physical process. A direct calculation of the evolution of the Coulomb stress before and during precursors nucleation shows large variations across the sample, explaining why earthquake forecasting methods based only on accumulated slip and Coulomb stress monitoring are often ineffective.

  17. Use of plankton-derived vitamin B1 precursors, especially thiazole-related precursor, by key marine picoeukaryotic phytoplankton

    PubMed Central

    Paerl, Ryan W; Bouget, Francois-Yves; Lozano, Jean-Claude; Vergé, Valérie; Schatt, Philippe; Allen, Eric E; Palenik, Brian; Azam, Farooq

    2017-01-01

    Several cosmopolitan marine picoeukaryotic phytoplankton are B1 auxotrophs requiring exogenous vitamin B1 or precursor to survive. From genomic evidence, representatives of picoeukaryotic phytoplankton (Ostreococcus and Micromonas spp.) were predicted to use known thiazole and pyrimidine B1 precursors to meet their B1 demands, however, recent culture-based experiments could not confirm this assumption. We hypothesized these phytoplankton strains could grow on precursors alone, but required a thiazole-related precursor other the well-known and extensively tested 4-methyl-5-thiazoleethanol. This hypothesis was tested using bioassays and co-cultures of picoeukaryotic phytoplankton and bacteria. We found that specific B1-synthesizing proteobacteria and phytoplankton are sources of a yet-to-be chemically identified thiazole-related precursor(s) that, along with pyrimidine B1 precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine, can support growth of Ostreococcus spp. (also Micromonas spp.) without B1. We additionally found that the B1-synthesizing plankton do not require contact with picoeukaryotic phytoplankton cells to produce thiazole-related precursor(s). Experiments with wild-type and genetically engineered Ostreococcus lines revealed that the thiazole kinase, ThiM, is required for growth on precursors, and that thiazole-related precursor(s) accumulate to appreciable levels in the euphotic ocean. Overall, our results point to thiazole-related B1 precursors as important micronutrients promoting the survival of abundant phytoplankton influencing surface ocean production and biogeochemical cycling. PMID:27935586

  18. Use of plankton-derived vitamin B1 precursors, especially thiazole-related precursor, by key marine picoeukaryotic phytoplankton.

    PubMed

    Paerl, Ryan W; Bouget, Francois-Yves; Lozano, Jean-Claude; Vergé, Valérie; Schatt, Philippe; Allen, Eric E; Palenik, Brian; Azam, Farooq

    2017-03-01

    Several cosmopolitan marine picoeukaryotic phytoplankton are B1 auxotrophs requiring exogenous vitamin B1 or precursor to survive. From genomic evidence, representatives of picoeukaryotic phytoplankton (Ostreococcus and Micromonas spp.) were predicted to use known thiazole and pyrimidine B1 precursors to meet their B1 demands, however, recent culture-based experiments could not confirm this assumption. We hypothesized these phytoplankton strains could grow on precursors alone, but required a thiazole-related precursor other the well-known and extensively tested 4-methyl-5-thiazoleethanol. This hypothesis was tested using bioassays and co-cultures of picoeukaryotic phytoplankton and bacteria. We found that specific B1-synthesizing proteobacteria and phytoplankton are sources of a yet-to-be chemically identified thiazole-related precursor(s) that, along with pyrimidine B1 precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine, can support growth of Ostreococcus spp. (also Micromonas spp.) without B1. We additionally found that the B1-synthesizing plankton do not require contact with picoeukaryotic phytoplankton cells to produce thiazole-related precursor(s). Experiments with wild-type and genetically engineered Ostreococcus lines revealed that the thiazole kinase, ThiM, is required for growth on precursors, and that thiazole-related precursor(s) accumulate to appreciable levels in the euphotic ocean. Overall, our results point to thiazole-related B1 precursors as important micronutrients promoting the survival of abundant phytoplankton influencing surface ocean production and biogeochemical cycling.

  19. 40 CFR 766.38 - Reporting on precursor chemical substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical...

  20. 40 CFR 766.38 - Reporting on precursor chemical substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical...

  1. 40 CFR 766.38 - Reporting on precursor chemical substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical...

  2. Amyloid precursor protein and amyloid precursor-like protein 2 in cancer

    PubMed Central

    Pandey, Poomy; Sliker, Bailee; Peters, Haley L.; Tuli, Amit; Herskovitz, Jonathan; Smits, Kaitlin; Purohit, Abhilasha; Singh, Rakesh K.; Dong, Jixin; Batra, Surinder K.; Coulter, Donald W.; Solheim, Joyce C.

    2016-01-01

    Amyloid precursor protein (APP) and its family members amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are type 1 transmembrane glycoproteins that are highly conserved across species. The transcriptional regulation of APP and APLP2 is similar but not identical, and the cleavage of both proteins is regulated by phosphorylation. APP has been implicated in Alzheimer's disease causation, and in addition to its importance in neurology, APP is deregulated in cancer cells. APLP2 is likewise overexpressed in cancer cells, and APLP2 and APP are linked to increased tumor cell proliferation, migration, and invasion. In this present review, we discuss the unfolding account of these APP family members’ roles in cancer progression and metastasis. PMID:26840089

  3. Meat flavor precursors and factors influencing flavor precursors--A systematic review.

    PubMed

    Khan, Muhammad Issa; Jo, Cheorun; Tariq, Muhammad Rizwan

    2015-12-01

    Flavor is the sensory impression sensed by taste and smell buds and is a leading factor determining the meat quality and purchasing decision of the consumer. Meat flavor is characteristic of volatiles produced as a result of reactions of non-volatile components that are induced thermally. The water soluble compounds having low molecular weight and meat lipids are important precursors of cooked meat flavor. The Maillard reaction, lipid oxidation, and vitamin degradation are leading reactions during cooking which develop meat flavor from uncooked meat with little aroma and bloody taste. The pre-slaughter and postmortem factors like animal breed, sex, age, feed, aging and cooking conditions contribute to flavor development of cooked meat. The objective of this review is to highlight the flavor chemistry, meat flavor precursors and factors affecting meat flavor precursors.

  4. Preparation of boron nitride fiber by organic precursor method

    NASA Astrophysics Data System (ADS)

    Zhou, Yingying; Sun, Runjun; Zhang, Zhaohuan; Fan, Wei; Zhou, Dan; Sheng, Cuihong

    In this paper, boron nitride polymer precursor was made by boric acid, melamine, twelve sodium alkyl sulfate as raw materials and pure water as medium which is heated to 70 °C. Boron nitride precursor polymer was soluble in formic acid solution. The boron nitride precursor can be electrostatically spun at the voltage in 23 kV and the distance between the positive and negative poles is 15 cm. The formed fiber is very uniform. The properties of the precursors were analyzed through electron microscope, infrared spectrum, X-ray and ultraviolet spectrum. The aim of the job is to got the precursor of BN and spun it.

  5. Systems and methods for detection of blowout precursors in combustors

    DOEpatents

    Lieuwen, Tim C.; Nair, Suraj

    2006-08-15

    The present invention comprises systems and methods for detecting flame blowout precursors in combustors. The blowout precursor detection system comprises a combustor, a pressure measuring device, and blowout precursor detection unit. A combustion controller may also be used to control combustor parameters. The methods of the present invention comprise receiving pressure data measured by an acoustic pressure measuring device, performing one or a combination of spectral analysis, statistical analysis, and wavelet analysis on received pressure data, and determining the existence of a blowout precursor based on such analyses. The spectral analysis, statistical analysis, and wavelet analysis further comprise their respective sub-methods to determine the existence of blowout precursors.

  6. The Mars 2001 Athena Precursor Experiment (APEX)

    NASA Technical Reports Server (NTRS)

    Squyres, S. W.; Arvidson, R.; Bell, J. F., III; Carr, M.; Christensen, P.; DesMarais, D.; dUston, C.; Economou, T.; Gorevan, S.; Klingelhoefer, G.

    1999-01-01

    The Athena Precursor Experiment (APEX) is a suite of scientific instruments for the Mars Surveyor Program 2001 (MSP'01) lander. The major elements of the APEX pay load are: (1) Pancam/Mini-TES, a combined stereo color imager and mid-infrared point spectrometer. (2) An Alpha-Proton-X-Ray Spectrometer (APXS) for in-situ elemental analysis. (3) A Mossbauer Spectrometer for in-situ determination of the mineralogy of Fe-bearing rocks and soils. (4) A Magnet Array that can separate magnetic soil particles from non-magnetic ones.

  7. Materials Design Through Chemical Control of Precursors

    DTIC Science & Technology

    2008-08-22

    C. L. Dezelah IV, P. Myllymäki, J. Päiväsaari, K. Arstila, L. Niinistö, and C. H. Winter, J. Mater. Chem. 2007, 17, 1308-1315. 11. “A Pyrazolate ...Helsinki University of Technology, May 9, 2007. 7. “A Pyrazolate -Based Metalorganic Tantalum Precursor Exhibiting High Thermal Stability and its Use...complexes that contain b-diketiminate and pyrazolate ligands (“Synthesis, Structure, and Ligand Redistribution Equilibria of Mixed Ligand Complexes of

  8. RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area.

    PubMed

    Labouèbe, Gwenaël; Lomazzi, Marta; Cruz, Hans G; Creton, Cyril; Luján, Rafael; Li, Meng; Yanagawa, Yuchio; Obata, Kunihiko; Watanabe, Masahiko; Wickman, Kevin; Boyer, Stephanie B; Slesinger, Paul A; Lüscher, Christian

    2007-12-01

    Agonists of GABA(B) receptors exert a bi-directional effect on the activity of dopamine (DA) neurons of the ventral tegmental area, which can be explained by the fact that coupling between GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK) channels is significantly weaker in DA neurons than in GABA neurons. Thus, low concentrations of agonists preferentially inhibit GABA neurons and thereby disinhibit DA neurons. This disinhibition might confer reinforcing properties on addictive GABA(B) receptor agonists such as gamma-hydroxybutyrate (GHB) and its derivatives. Here we show that, in DA neurons of mice, the low coupling efficiency reflects the selective expression of heteromeric GIRK2/3 channels and is dynamically modulated by a member of the regulator of G protein signaling (RGS) protein family. Moreover, repetitive exposure to GHB increases the GABA(B) receptor-GIRK channel coupling efficiency through downregulation of RGS2. Finally, oral self-administration of GHB at a concentration that is normally rewarding becomes aversive after chronic exposure. On the basis of these results, we propose a mechanism that might underlie tolerance to GHB.

  9. Precursors of eruptions at Vesuvius (Italy)

    NASA Astrophysics Data System (ADS)

    Scandone, Roberto; Giacomelli, Lisetta

    2008-04-01

    The historical record of activity of Mount Vesuvius is uncommonly long and may serve as a guide to understand precursors before the outbreak of new activity. Reposes of different lengths have been observed in the past, with long ones preceding violent explosive eruptions. Eruptions occurring during periods of permanent activity have been preceded by possible deformation of the volcanic edifice and by short duration, earthquake swarms. Otherwise they have occurred without any reported precursors. The renewal of activity after long periods, like the current one, has been preceded by unrest lasting years to weeks, as a new eruption would require connection to the surface of a reservoir at depth ranging between 6 and 4 km. Since 1944, episodic seismic swarms, have occurred with a frequency similar to that of the violent strombolian eruptions during the last period of permanent activity; they are interpreted as intrusions and arrest of magma batches into a reservoir at the same depth of that feeding past sub-plinian eruptions.

  10. Ascorbate as a Biosynthetic Precursor in Plants

    PubMed Central

    Debolt, Seth; Melino, Vanessa; Ford, Christopher M.

    2007-01-01

    Background and Aims l-Ascorbate (vitamin C) has well-documented roles in many aspects of redox control and anti-oxidant activity in plant cells. This Botanical Briefing highlights recent developments in another aspect of l-ascorbate metabolism: its function as a precursor for specific processes in the biosynthesis of organic acids. Scope The Briefing provides a summary of recent advances in our understanding of l-ascorbate metabolism, covering biosynthesis, translocation and functional aspects. The role of l-ascorbate as a biosynthetic precursor in the formation of oxalic acid, l-threonic acid and l-tartaric acid is described, and progress in elaborating the mechanisms of the formation of these acids is reviewed. The potential conflict between the two roles of l-ascorbate in plant cells, functional and biosynthetic, is highlighted. Conclusions Recent advances in the understanding of l-ascorbate catabolism and the formation of oxalic and l-tartaric acids provide compelling evidence for a major role of l-ascorbate in plant metabolism. Combined experimental approaches, using classic biochemical and emerging ‘omics’ technologies, have provided recent insight to previously under-investigated areas. PMID:17098753

  11. Precursor solitons in a flowing complex plasma

    NASA Astrophysics Data System (ADS)

    Bandyopadhyay, Pintu; Jaiswal, Surabhi; Sen, Abhijit

    2015-11-01

    We report the first experimental observation of precursor solitons in a flowing dusty plasma. The nonlinear solitary dust acoustic waves (DAWs) are excited by a supersonic mass flow of the dust particles passing over an electrostatic potential hill. In a frame where the fluid is stationary and the hill is moving the solitons propagate in the upstream direction while wake structures consisting of linear DAWs are seen to propagate in the downstream direction. The experiments have been carried out in a U-shaped Dusty Plasma Experimental (DPEx) device where kaolin particles are immersed in a DC discharge argon plasma to form the dusty plasma and a floating wire mounted on the cathode creates a potential hill. The dust flow is induced by sudden changes in the hill height and the solitary structures are seen only for supersonic flows and up to an upper limit of the flow. A theoretical model description of the phenomenon will be provided and some practical implications of such precursor excitations for a charged object moving in a plasma will be discussed.

  12. Diagenesis and catagenesis of marine kerogen precursors

    SciTech Connect

    Rafalska-Bloch, J.

    1987-01-01

    The approaches used were (1) investigations of marine kerogen precursors in a natural environment, e.g., in reefal carbonate sediments (in Puerto Rico and Belize) and (2) laboratory modeling of the condensation of marine kerogen precursors, i.e., amino acids and sugars and subsequent formation and reactions of melanoidin polymers. The organic facies model of a reef environment was developed from the analysis of (1) total organic carbon, (2) visual protokerogen types, (3) Rock-Eval indices and (4) sedimentological considerations. Rates of melanoidin formation, incorporation of amino acid and glucose into the melanoidin polymers and their attendant decrease in the melanoidin solutions were evaluated. The observed pattern was that of initially rapid loss of biomonomers from the melanoidin solutions and concomitant formation of melanoidin polymers. The rate of incorporation of amino acids into the polymers is related partly to glucose concentration and partly to the type of amino acid. The racemization rates of amino acids were also investigated. During the course of melanoidin formation the original amino acid abundances and stereochemistry are redistributed during simulated diagenesis. This may have implications for natural environments where diagenesis may obscure the original depositional signal and complicate geochronological studies. Catagenetic evolution of both synthetic geopolymer (lysine, histidine, arginine, glucose - melanoidin) and natural geopolymers (Belizian organic matter) was simulated using hydrous pyrolysis.

  13. Mars MetNet Precursor Mission Status

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

    2013-09-01

    We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  14. Filler/ Polycarbosilane Systems as CMC Matrix Precursors

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.

    1998-01-01

    Pyrolytic conversion of polymeric precursors to ceramics is accompanied by loss of volatiles and large volume changes. Infiltration of a low viscosity polymer into a fiber preform will fill small spaces within fiber tows by capillary forces, but create large matrix cracks within large, intertow areas. One approach to minimizing shrinkage and reducing the number of required infiltration cycles is to use particulate fillers. In this study, Starfire allylhydridopolycarbosilane (AHPCS) was blended with a silicon carbide powder, with and without dispersant, using shear mixing. The polymer and polymer/particle interactions were characterized using nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis and rheometry. Polymer/particulate slurries and suspensions were used to infiltrate a figidized preform of an eight ply five harness satin CG Nicalon fiber having a dual layer BN/SiC interface coating, and the resulting composites characterized by optical and scanning electron microscopy.

  15. Silsesquioxanes as precursors to ceramic composites

    NASA Technical Reports Server (NTRS)

    Hurwitz, Frances I.; Hyatt, Lizbeth H.; Gorecki, Joy; Damore, Lisa

    1987-01-01

    Silsesquioxanes having the general structure RSiO sub 1.5, where R = methyl, propyl, or phenyl, melt flow at 70 to 100 C. Above 100 C, free -OH groups condense. At 225 C further crosslinking occurs, and the materials form thermosets. Pyrolysis, with accompanying loss of volatiles, takes place at nominally 525 C. At higher temperatures, the R group serves as an internal carbon soruce for carbo-thermal reduction to SiC accompanied by the evolution of CO. By blending silsesquioxanes with varying R groups, both the melt rheology and composition of the fired ceramic can be controlled. Fibers can be spun from the melt which are stable in argon in 1400 C. The silsesquioxanes also were used as matrix precursors for Nicalon and alpha-SiC platelet reinforced composites.

  16. Design of Aerosol Coating Reactors: Precursor Injection

    PubMed Central

    Buesser, Beat; Pratsinis, Sotiris E.

    2013-01-01

    Particles are coated with thin shells to facilitate their processing and incorporation into liquid or solid matrixes without altering core particle properties (coloristic, magnetic, etc.). Here, computational fluid and particle dynamics are combined to investigate the geometry of an aerosol reactor for continuous coating of freshly-made titanium dioxide core nanoparticles with nanothin silica shells by injection of hexamethyldisiloxane (HMDSO) vapor downstream of TiO2 particle formation. The focus is on the influence of HMDSO vapor jet number and direction in terms of azimuth and inclination jet angles on process temperature and coated particle characteristics (shell thickness and fraction of uncoated particles). Rapid and homogeneous mixing of core particle aerosol and coating precursor vapor facilitates synthesis of core-shell nanoparticles with uniform shell thickness and high coating efficiency (minimal uncoated core and free coating particles). PMID:23658471

  17. Precursor conditions related to Zimbabwe's summer droughts

    NASA Astrophysics Data System (ADS)

    Nangombe, Shingirai; Madyiwa, Simon; Wang, Jianhong

    2016-11-01

    Despite the increasing severity of droughts and their effects on Zimbabwe's agriculture, there are few tools available for predicting these droughts in advance. Consequently, communities and farmers are more exposed, and policy makers are always ill prepared for such. This study sought to investigate possible cycles and precursor meteorological conditions prior to drought seasons that could be used to predict impending droughts in Zimbabwe. The Single Z-Index was used to identify and grade drought years between 1951 and 2010 according to rainfall severity. Spectral analysis was used to reveal the cycles of droughts for possible use of these cycles for drought prediction. Composite analysis was used to investigate circulation and temperature anomalies associated with severe and extreme drought years. Results indicate that severe droughts are more highly correlated with circulation patterns and embedded weather systems in the Indian Ocean and equatorial Pacific Ocean than any other area. This study identified sea surface temperatures in the average period June to August, geopotential height and wind vector in July to September period, and air temperature in September to November period as precursors that can be used to predict a drought occurrence several months in advance. Therefore, in addition to sea surface temperature, which was identified through previous research for predicting Zimbabwean droughts, the other parameters identified in this study can aid in drought prediction. Drought cycles were established at 20-, 12.5-, 3.2-, and 2.7-year cycles. The spectral peaks, 12.5, 3.2, and 2.7, had a similar timescale with the luni-solar tide, El Niño Southern Oscillation and Quasi Biennial Oscillation, respectively, and hence, occurrence of these phenomena have a possibility of indicating when the next drought might be.

  18. Diamond films grown from fullerene precursors

    SciTech Connect

    Gruen, D.M.; Zuiker, C.D.; Krauss, A.R.

    1995-07-01

    Fullerene precursors have been shown to result in the growth of diamond films from argon microwave plasmas. In contradistinction to most diamond films grown using conventional methane-hydrogen mixtures, the fullerene-generated films are nanocrystalline and smooth on the nanometer scale. They have recently been shown to have friction coefficients approaching the values of natural diamond. It is clearly important to understand the development of surface morphology during film growth from fullerene precursors and to elucidate the factors leading to surface roughness when hydrogen is present in the chemical vapor deposition (CVD) gas mixtures. To achieve these goals, we are measuring surface reflectivity of diamond films growing on silicon substrates over a wide range of plasma processing conditions. A model for the interpretation of the laser interferometric data has been developed, which allows one to determine film growth rate, rms surface roughness, and bulk losses due to scattering and absorption. The rms roughness values determined by reflectivity are in good agreement with atomic force microscope (AFM) measurements. A number of techniques, including high-resolution transmission electron microscopy (HRTEM) and near-edge x-ray absorption find structure (NEXAFS) measurements, have been used to characterize the films. A mechanism for diamond-film growth involving the C{sub 2} molecule as a growth species will be presented. The mechanism is based on (1) the observation that the optical emission spectra of the fullerene- containing plasmas are dominated by the Swan bands of C{sub 2} and (2) the ability of C{sub 2} to insert directly into C-H and C-C bonds with low activation barriers, as shown by recent theoretical calculations of reactions of C{sub 2} with carbon clusters.

  19. Nanomechanics controls neuronal precursors adhesion and differentiation.

    PubMed

    Migliorini, Elisa; Ban, Jelena; Grenci, Gianluca; Andolfi, Laura; Pozzato, Alessandro; Tormen, Massimo; Torre, Vincent; Lazzarino, Marco

    2013-08-01

    The ability to control the differentiation of stem cells into specific neuronal types has a tremendous potential for the treatment of neurodegenerative diseases. In vitro neuronal differentiation can be guided by the interplay of biochemical and biophysical cues. Different strategies to increase the differentiation yield have been proposed, focusing everything on substrate topography, or, alternatively on substrate stiffness. Both strategies demonstrated an improvement of the cellular response. However it was often impossible to separate the topographical and the mechanical contributions. Here we investigate the role of the mechanical properties of nanostructured substrates, aiming at understanding the ultimate parameters which govern the stem cell differentiation. To this purpose a set of different substrates with controlled stiffness and with or without nanopatterning are used for stem cell differentiation. Our results show that the neuronal differentiation yield depends mainly on the substrate mechanical properties while the geometry plays a minor role. In particular nanostructured and flat polydimethylsiloxane (PDMS) substrates with comparable stiffness show the same neuronal yield. The improvement in the differentiation yield obtained through surface nanopatterning in the submicrometer scale could be explained as a consequence of a substrate softening effect. Finally we investigate by single cell force spectroscopy the neuronal precursor adhesion on the substrate immediately after seeding, as a possible critical step governing the neuronal differentiation efficiency. We observed that neuronal precursor adhesion depends on substrate stiffness but not on surface structure, and in particular it is higher on softer substrates. Our results suggest that cell-substrate adhesion forces and mechanical response are the key parameters to be considered for substrate design in neuronal regenerative medicine.

  20. Precursors to glycogen in ovine fetuses

    SciTech Connect

    Levitsky, L.L.; Paton, J.B.; Fisher, D.E. )

    1988-11-01

    Postprandial hepatic glycogenesis in the adult animal is now felt to proceed largely through gluconeogenic pathways rather than directly from glucose. The ovine fetus, like the mature sheep, lacks specific hepatic glucokinase. Therefore, the authors examined the role of lactate as a fetal glycogenic precursor in seven chronically catheterized 125-day sheep fetuses. Fetuses were infused with L-(U-{sup 14}C)lactate and D-(3-{sup 3}H)glucose, while maternal glucose was maintained at 50 mg/dl. Mean fetal hepatic glycogen specific activity ({mu}Ci/mg {times} 10{sup 3}) was 0.82 {plus minus} 0.08 for {sup 14}C and 2.6 {plus minus} 0.4 for {sup 3}H, whereas fetal renal glycogen specific activity was 0.46 {plus minus} 0.22 for {sup 14}C and 0.78 {plus minus} 0.16 for {sup 3}H. In contrast, ({sup 14}C)glucose specific activity was undetectable in blood and mean ({sup 3}H)glucose specific activity was 8.9 {plus minus} 1.3 {mu}Ci/mg {times} 10{sup 3}. The least detectable specific activity of ({sup 14}C)glucose did not differ significantly from the ({sup 14}C)glycogen enrichment in liver, whereas ({sup 3}H)glucose specific activity was significantly greater than ({sup 3}H)glycogen enrichment. The authors conclude that glycogenesis from glucose is partly through the indirect gluconeogenic route and that lactate may be a glycogenic precursor in the ovine fetus.

  1. Thermal Stability of Jet Fuels: Kinetics of Forming Deposit Precursors

    NASA Technical Reports Server (NTRS)

    Naegeli, David W.

    1997-01-01

    The focus of this study was on the autoxidation kinetics of deposit precursor formation in jet fuels. The objectives were: (1) to demonstrate that laser-induced fluorescence is a viable kinetic tool for measuring rates of deposit precursor formation in jet fuels; (2) to determine global rate expressions for the formation of thermal deposit precursors in jet fuels; and (3) to better understand the chemical mechanism of thermal stability. The fuels were isothermally stressed in small glass ampules in the 120 to 180 C range. Concentrations of deposit precursor, hydroperoxide and oxygen consumption were measured over time in the thermally stressed fuels. Deposit precursors were measured using laser-induced fluorescence (LIF), hydroperoxides using a spectrophotometric technique, and oxygen consumption by the pressure loss in the ampule. The expressions, I.P. = 1.278 x 10(exp -11)exp(28,517.9/RT) and R(sub dp) = 2.382 x 10(exp 17)exp(-34,369.2/RT) for the induction period, I.P. and rate of deposit precursor formation R(sub dp), were determined for Jet A fuel. The results of the study support a new theory of deposit formation in jet fuels, which suggest that acid catalyzed ionic reactions compete with free radical reactions to form deposit precursors. The results indicate that deposit precursors form only when aromatics are present in the fuel. Traces of sulfur reduce the rate of autoxidation but increase the yield of deposit precursor. Free radical chemistry is responsible for hydroperoxide formation and the oxidation of sulfur compounds to sulfonic acids. Phenols are then formed by the acid catalyzed decomposition of benzylic hydroperoxides, and deposit precursors are produced by the reaction of phenols with aldehydes, which forms a polymer similar to Bakelite. Deposit precursors appear to have a phenolic resin-like structure because the LIF spectra of the deposit precursors were similar to that of phenolic resin dissolved in TAM.

  2. Frog Swarms: Earthquake Precursors or False Alarms?

    PubMed Central

    Grant, Rachel A.; Conlan, Hilary

    2013-01-01

    Simple Summary Media reports linking unusual animal behaviour with earthquakes can potentially create false alarms and unnecessary anxiety among people that live in earthquake risk zones. Recently large frog swarms in China and elsewhere have been reported as earthquake precursors in the media. By examining international media reports of frog swarms since 1850 in comparison to earthquake data, it was concluded that frog swarms are naturally occurring dispersal behaviour of juveniles and are not associated with earthquakes. However, the media in seismic risk areas may be more likely to report frog swarms, and more likely to disseminate reports on frog swarms after earthquakes have occurred, leading to an apparent link between frog swarms and earthquakes. Abstract In short-term earthquake risk forecasting, the avoidance of false alarms is of utmost importance to preclude the possibility of unnecessary panic among populations in seismic hazard areas. Unusual animal behaviour prior to earthquakes has been reported for millennia but has rarely been scientifically documented. Recently large migrations or unusual behaviour of amphibians have been linked to large earthquakes, and media reports of large frog and toad migrations in areas of high seismic risk such as Greece and China have led to fears of a subsequent large earthquake. However, at certain times of year large migrations are part of the normal behavioural repertoire of amphibians. News reports of “frog swarms” from 1850 to the present day were examined for evidence that this behaviour is a precursor to large earthquakes. It was found that only two of 28 reported frog swarms preceded large earthquakes (Sichuan province, China in 2008 and 2010). All of the reported mass migrations of amphibians occurred in late spring, summer and autumn and appeared to relate to small juvenile anurans (frogs and toads). It was concluded that most reported “frog swarms” are actually normal behaviour, probably caused by

  3. Time resolved spectral behavior of bright BATSE precursors

    NASA Astrophysics Data System (ADS)

    Burlon, D.; Ghirlanda, G.; Ghisellini, G.; Greiner, J.; Celotti, A.

    2009-10-01

    Aims: Gamma ray bursts (GRBs) are sometimes preceded by dimmer emission episodes, called “precursors”, whose nature is still a puzzle: they could either have the same origin as the main emission episode or they could be due to another mechanism. We investigate if precursors have some spectral distinctive feature with respect to the main GRB episodes. Methods: To this aim we compare the spectral evolution of the precursor with that of the main GRB event. We also study if and how the spectral parameters, and in particular the peak of the ν Fν spectrum of time resolved spectra, correlates with the flux. This allows us to test if the spectra of the precursor and of the main event belong to the same correlation (if any). We searched GRBs with precursor activity in the complete sample of 2704 bursts detected by BATSE finding that 12% of GRBs have one or more precursors. Among these we considered the bursts with time resolved spectral analysis performed by Kaneko et al. ( 2006, ApJS, 166, 298), selecting those having at least two time resolved spectra for the precursor. Results: We find that precursors and main events have very similar spectral properties. The spectral evolution within precursors has similar trends as the spectral evolution observed in the subsequent peaks. Also the typical spectral parameters of the precursors are similar to those of the main GRB events. Moreover, in several cases we find that within the precursors the peak energy of the spectrum is correlated with the flux similarly to what happens in the main GRB event. This strongly favors models in which the precursor is due to the same fireball physics of the main emission episodes. Figures 8 to 41 are only available in electronic form at http://www.aanda.org

  4. Assimilation of NAD(+) precursors in Candida glabrata.

    PubMed

    Ma, Biao; Pan, Shih-Jung; Zupancic, Margaret L; Cormack, Brendan P

    2007-10-01

    The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD(+)) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD(+). C. glabrata salvage pathways defined in this article allow NAD(+) to be synthesized from three compounds - nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss-Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss-Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss-Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD(+) via the nicotinamidase Pnc1 and the Preiss-Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD(+) sources during disseminated infection.

  5. Robotic Precursor Missions for Mars Habitats

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terry; Pirjanian, Paolo; Schenker, Paul S.; Trebi-Ollennu, Ashitey; Das, Hari; Joshi, Sajay

    2000-01-01

    Infrastructure support for robotic colonies, manned Mars habitat, and/or robotic exploration of planetary surfaces will need to rely on the field deployment of multiple robust robots. This support includes such tasks as the deployment and servicing of power systems and ISRU generators, construction of beaconed roadways, and the site preparation and deployment of manned habitat modules. The current level of autonomy of planetary rovers such as Sojourner will need to be greatly enhanced for these types of operations. In addition, single robotic platforms will not be capable of complicated construction scenarios. Precursor robotic missions to Mars that involve teams of multiple cooperating robots to accomplish some of these tasks is a cost effective solution to the possible long timeline necessary for the deployment of a manned habitat. Ongoing work at JPL under the Mars Outpost Program in the area of robot colonies is investigating many of the technology developments necessary for such an ambitious undertaking. Some of the issues that are being addressed include behavior-based control systems for multiple cooperating robots (CAMPOUT), development of autonomous robotic systems for the rescue/repair of trapped or disabled robots, and the design and development of robotic platforms for construction tasks such as material transport and surface clearing.

  6. A Fission-Powered Interstellar Precursor Mission

    SciTech Connect

    Lenard, R.X.; Lipinski, R.J.; West, J.L.; Wright, S.A.

    1998-10-28

    An 'interstellar precursor mission' lays the groundwork for eventual interstellar exploration by studying the interstellar medium and by stretching technologies that have potential application for eventual interstellar exploration. The numerous scientific goals for such a mission include generating a 3-D stellar map of our galaxy, studying Kuiper-belt and Oort cloud objects, and observing distant objects using the sun's gravitational lens as the primary of an enormous telescope. System equations are developed for a space tug which propels a 2500-kg scientific payload to 550 astronomical units in about 20 years. The tug to transport this payload uses electric propulsion with an Isp of 15,000 seconds and a fission reactor with a closed Brayton cycle to genemte the electricity. The optimal configuration may be to thrust for only about 6 years and then coast for the remaining 14 pars. This spacecraft does not require any physics breakthroughs or major advances in technology. The fission power syslem can be engineered and built by drawing upon known technologies developed for relatgd systems over the past 40 years. The tug system would eventually reach 1000 a.u in 33 years, and would have adequate power to relay large amounts of data throughout its journey.

  7. A fission-powered interstellar precursor mission

    SciTech Connect

    Lipinski, Ronald J.; Lenard, Roger X.; Wright, Steven A. West, John L.

    1999-01-01

    An {open_quotes}interstellar precursor mission{close_quotes} lays the groundwork for eventual interstellar exploration by studying the interstellar medium and by stretching technologies that have potential application for eventual interstellar exploration. The numerous scientific goals for such a mission include generating a 3-D stellar map of our galaxy, studying Kuiper-belt and Oort cloud objects, and observing distant objects using the sun{close_quote}s gravitational lens as the primary of an enormous telescope. System equations are developed for a space tug which propels a 2500-kg scientific payload to 550 astronomical units in about 20 years. The tug to transport this payload uses electric propulsion with an lsp of 15,000 seconds and a fission reactor with a closed Brayton cycle to generate the electricity. The optimal configuration may be to thrust for only about 6 years and then coast for the remaining 14 years. This spacecraft does not require any physics breakthroughs or major advances in technology. The fission power system can be engineered and built by drawing upon known technologies developed for related systems over the past 40 years. The tug system would eventually reach 1000 a.u in 33 years, and would have adequate power to relay large amounts of data throughout its journey. {copyright} {ital 1999 American Institute of Physics.}

  8. Biodegradable mesoporous delivery system for biomineralization precursors

    PubMed Central

    Yang, Hong-ye; Niu, Li-na; Sun, Jin-long; Huang, Xue-qing; Pei, Dan-dan; Huang, Cui; Tay, Franklin R

    2017-01-01

    Scaffold supplements such as nanoparticles, components of the extracellular matrix, or growth factors have been incorporated in conventional scaffold materials to produce smart scaffolds for tissue engineering of damaged hard tissues. Due to increasing concerns on the clinical side effects of using large doses of recombinant bone-morphogenetic protein-2 in bone surgery, it is desirable to develop an alternative nanoscale scaffold supplement that is not only osteoinductive, but is also multifunctional in that it can perform other significant bone regenerative roles apart from stimulation of osteogenic differentiation. Because both amorphous calcium phosphate (ACP) and silica are osteoinductive, a biodegradable, nonfunctionalized, expanded-pore mesoporous silica nanoparticle carrier was developed for loading, storage, and sustained release of a novel, biosilicification-inspired, polyamine-stabilized liquid precursor phase of ACP for collagen biomineralization and for release of orthosilicic acid, both of which are conducive to bone growth. Positively charged poly(allylamine)-stabilized ACP (PAH-ACP) could be effectively loaded and released from nonfunctionalized expanded-pore mesoporous silica nanoparticles (pMSN). The PAH-ACP released from loaded pMSN still retained its ability to infiltrate and mineralize collagen fibrils. Complete degradation of pMSN occurred following unloading of their PAH-ACP cargo. Because PAH-ACP loaded pMSN possesses relatively low cytotoxicity to human bone marrow-derived mesenchymal stem cells, these nanoparticles may be blended with any osteoconductive scaffold with macro- and microporosities as a versatile scaffold supplement to enhance bone regeneration. PMID:28182119

  9. Robotic Precursor Missions for Mars Habitats

    NASA Astrophysics Data System (ADS)

    Huntsberger, Terry; Pirjanian, Paolo; Schenker, Paul S.; Trebi-Ollennu, Ashitey; Das, Hari; Joshi, Sajay

    2000-07-01

    Infrastructure support for robotic colonies, manned Mars habitat, and/or robotic exploration of planetary surfaces will need to rely on the field deployment of multiple robust robots. This support includes such tasks as the deployment and servicing of power systems and ISRU generators, construction of beaconed roadways, and the site preparation and deployment of manned habitat modules. The current level of autonomy of planetary rovers such as Sojourner will need to be greatly enhanced for these types of operations. In addition, single robotic platforms will not be capable of complicated construction scenarios. Precursor robotic missions to Mars that involve teams of multiple cooperating robots to accomplish some of these tasks is a cost effective solution to the possible long timeline necessary for the deployment of a manned habitat. Ongoing work at JPL under the Mars Outpost Program in the area of robot colonies is investigating many of the technology developments necessary for such an ambitious undertaking. Some of the issues that are being addressed include behavior-based control systems for multiple cooperating robots (CAMPOUT), development of autonomous robotic systems for the rescue/repair of trapped or disabled robots, and the design and development of robotic platforms for construction tasks such as material transport and surface clearing.

  10. Pair fireball precursors of neutron star mergers

    NASA Astrophysics Data System (ADS)

    Metzger, Brian D.; Zivancev, Charles

    2016-10-01

    If at least one neutron star (NS) is magnetized in a binary NS merger, then the orbital motion of the conducting companion during the final inspiral induces a strong voltage and current along the magnetic field lines connecting the NSs. If a modest fraction η of the extracted electromagnetic power extracted accelerates relativistic particles, the resulting gamma-ray emission a compact volume will result in the formation of an electron-positron pair fireball. Applying a steady-state pair wind model, we quantify the detectability of the precursor fireball with gamma-ray satellites. For η ˜ 1 the gamma-ray detection horizon of Dmax ≈ 10(Bd/1014 G)3/4 Mpc is much closer than the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo horizon of 200 Mpc, unless the NS surface magnetic field strength is very large, B_d ≲ 10^{15} G. Given the quasi-isotropic nature of the emission, mergers with weaker NS fields could contribute a nearby population of short gamma-ray bursts. Power not dissipated close to the binary is carried to infinity along the open field lines by a large-scale Poynting flux. Reconnection within this outflow, well outside of the pair photosphere, provides a potential site for non-thermal emission, such as a coherent millisecond radio burst.

  11. Cellular Metabolism of Unnatural Sialic Acid Precursors

    PubMed Central

    Pham, Nam D.; Fermaintt, Charles S.; Rodriguez, Andrea C.; McCombs, Janet E.; Nischan, Nicole; Kohler, Jennifer J.

    2015-01-01

    Carbohydrates, in addition to their metabolic functions, serve important roles as receptors, ligands, and structural molecules for diverse biological processes. Insight into carbohydrate biology and mechanisms has been aided by metabolic oligosaccharide engineering (MOE). In MOE, unnatural carbohydrate analogs with novel functional groups are incorporated into cellular glycoconjugates and used to probe biological systems. While MOE has expanded knowledge of carbohydrate biology, limited metabolism of unnatural carbohydrate analogs restricts its use. Here we assess metabolism of SiaDAz, a diazirine-modified analog of sialic acid, and its cell-permeable precursor, Ac4ManNDAz. We show that the efficiency of Ac4ManNDAz and SiaDAz metabolism depends on cell type. Our results indicate that different cell lines can have different metabolic roadblocks in the synthesis of cell surface SiaDAz. These findings point to roles for promiscuous intracellular esterases, kinases, and phosphatases during unnatural sugar metabolism and provide guidance for ways to improve MOE. PMID:25957566

  12. PRECURSORS TO INTERSTELLAR SHOCKS OF SOLAR ORIGIN

    SciTech Connect

    Gurnett, D. A.; Kurth, W. S.; Stone, E. C.; Cummings, A. C.; Krimigis, S. M.; Decker, R. B.; Burlaga, L. F.

    2015-08-20

    On or about 2012 August 25, the Voyager 1 spacecraft crossed the heliopause into the nearby interstellar plasma. In the nearly three years that the spacecraft has been in interstellar space, three notable particle and field disturbances have been observed, each apparently associated with a shock wave propagating outward from the Sun. Here, we present a detailed analysis of the third and most impressive of these disturbances, with brief comparisons to the two previous events, both of which have been previously reported. The shock responsible for the third event was first detected on 2014 February 17 by the onset of narrowband radio emissions from the approaching shock, followed on 2014 May 13 by the abrupt appearance of intense electron plasma oscillations generated by electrons streaming outward ahead of the shock. Finally, the shock arrived on 2014 August 25, as indicated by a jump in the magnetic field strength and the plasma density. Various disturbances in the intensity and anisotropy of galactic cosmic rays were also observed ahead of the shock, some of which are believed to be caused by the reflection and acceleration of cosmic rays by the magnetic field jump at the shock, and/or by interactions with upstream plasma waves. Comparisons to the two previous weaker events show somewhat similar precursor effects, although differing in certain details. Many of these effects are very similar to those observed in the region called the “foreshock” that occurs upstream of planetary bow shocks, only on a vastly larger spatial scale.

  13. The Amyloid Precursor Protein Controls PIKfyve Function.

    PubMed

    Balklava, Zita; Niehage, Christian; Currinn, Heather; Mellor, Laura; Guscott, Benjamin; Poulin, Gino; Hoflack, Bernard; Wassmer, Thomas

    2015-01-01

    While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease.

  14. Bacterial Cellular Materials as Precursors of Chloroform

    NASA Astrophysics Data System (ADS)

    Wang, J.; Ng, T.; Zhang, Q.; Chow, A. T.; Wong, P.

    2011-12-01

    The environmental sources of chloroform and other halocarbons have been intensively investigated because their effects of stratospheric ozone destruction and environmental toxicity. It has been demonstrated that microorganisms could facilitate the biotic generation of chloroform from natural organic matters in soil, but whether the cellular materials itself also serves as an important precursor due to photo-disinfection is poorly known. Herein, seven common pure bacterial cultures (Acinetobacter junii, Aeromonas hydrophila, Bacillus cereus, Bacillus substilis, Escherichia coli, Shigella sonnei, Staphylococcus sciuri) were chlorinated to evaluate the yields of chloroform, dibromochloromethane, dichlorobromomethane, and bromoform. The effects of bromide on these chemical productions and speciations were also investigated. Results showed that, on average, 5.64-36.42 μg-chloroform /mg-C were generated during the bacterial chlorination, in similar order of magnitude to that generated by humic acid (previously reported as 78 μg-chloroform/mg-C). However, unlike humic acid in water chlorination, chloroform concentration did not simply increase with the total organic carbon in water mixture. In the presence of bromide, the yield of brominated species responded linearly to the bromide concentration. This study provides useful information to understand the contributions of chloroform from photodisinfection processes in coastal environments.

  15. Mars MetNet Precursor Mission Status

    NASA Astrophysics Data System (ADS)

    Harri, Ari-Matti; Aleksashkin, Sergey; Guerrero, Héctor; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

    2013-04-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL), using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. For the precursor mission (MMPM) intended to verify the landing concept and key technology during a real Mars mission all qualification activities are completed and the payload and system flight model components are being manufactured. The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the descent phase starting shortly after separation from the spacecraft. Details of the current MMPM system and payload configuration and their performance parameters will be shown.

  16. A Procedure for Identifying Precursors to Problem Behavior

    ERIC Educational Resources Information Center

    Herscovitch, Brandon; Roscoe, Eileen M.; Libby, Myrna E.; Bourret, Jason C.; Ahearn, William H.

    2009-01-01

    We describe a procedure for differentiating among potential precursor responses for use in a functional analysis. Conditional probability analysis of descriptive assessment data identified three potential precursors. Results from the indirect assessment corresponded with those obtained from the descriptive assessment. The top-ranked response…

  17. Precursors to Aggression Are Evident by 6 Months of Age

    ERIC Educational Resources Information Center

    Hay, Dale F.; Waters, Cerith S.; Perra, Oliver; Swift, Naomi; Kairis, Victoria; Phillips, Rebecca; Jones, Roland; Goodyer, Ian; Harold, Gordon; Thapar, Anita; van Goozen, Stephanie

    2014-01-01

    We tested the hypothesis that developmental precursors to aggression are apparent in infancy. Up to three informants rated 301 firstborn infants for early signs of anger, hitting and biting; 279 (93%) were assessed again as toddlers. Informants' ratings were validated by direct observation at both ages. The precursor behaviours were…

  18. Topographical and Functional Properties of Precursors to Severe Problem Behavior

    ERIC Educational Resources Information Center

    Fahmie, Tara A.; Iwata, Brian A.

    2011-01-01

    A literature search identified 17 articles reporting data on 34 subjects who engaged in precursors to severe problem behavior, which we examined to identify topographical and functional characteristics. Unintelligible vocalization was the most common precursor to aggression (27%) and property destruction (29%), whereas self- or nondirected…

  19. Human embryonic epidermis contains a diverse Langerhans cell precursor pool.

    PubMed

    Schuster, Christopher; Mildner, Michael; Mairhofer, Mario; Bauer, Wolfgang; Fiala, Christian; Prior, Marion; Eppel, Wolfgang; Kolbus, Andrea; Tschachler, Erwin; Stingl, Georg; Elbe-Bürger, Adelheid

    2014-02-01

    Despite intense efforts, the exact phenotype of the epidermal Langerhans cell (LC) precursors during human ontogeny has not been determined yet. These elusive precursors are believed to migrate into the embryonic skin and to express primitive surface markers, including CD36, but not typical LC markers such as CD1a, CD1c and CD207. The aim of this study was to further characterize the phenotype of LC precursors in human embryonic epidermis and to compare it with that of LCs in healthy adult skin. We found that epidermal leukocytes in first trimester human skin are negative for CD34 and heterogeneous with regard to the expression of CD1c, CD14 and CD36, thus contrasting the phenotypic uniformity of epidermal LCs in adult skin. These data indicate that LC precursors colonize the developing epidermis in an undifferentiated state, where they acquire the definitive LC marker profile with time. Using a human three-dimensional full-thickness skin model to mimic in vivo LC development, we found that FACS-sorted, CD207(-) cord blood-derived haematopoietic precursor cells resembling foetal LC precursors but not CD14(+)CD16(-) blood monocytes integrate into skin equivalents, and without additional exogenous cytokines give rise to cells that morphologically and phenotypically resemble LCs. Overall, it appears that CD14(-) haematopoietic precursors possess a much higher differentiation potential than CD14(+) precursor cells.

  20. An Evaluation of Strengthening Precursors to Increase Preschooler Compliance

    ERIC Educational Resources Information Center

    Kraus, Aaron J.; Hanley, Gregory P.; Cesana, Lori L.; Eisenberg, Danielle; Jarvie, Adam C.

    2012-01-01

    We evaluated the strategy of increasing precursors to compliance on the compliance of 2 preschool boys. Modeling and differential reinforcement were used to increase specific responses to his name being called prior to the opportunity to comply with an instruction. The precursors were stopping the ongoing activity and orienting to, making eye…

  1. Precursors of Short GRBs Registered by SPI-ACS/INTEGRAL

    NASA Astrophysics Data System (ADS)

    Minaev, P.; Pozanenko, A.

    2016-10-01

    We have searched for precursors in light curves of short gamma-ray bursts registered by SPI-ACS/INTEGRAL in 2002-2014. The portion of short bursts with precursor activity will be less than 0.4% from all short bursts registered by SPI-ACS.

  2. Effects of rhythmic precursors on perception of stress/syllabicity

    NASA Astrophysics Data System (ADS)

    Stilp, Christian E.; Kluender, Keith R.

    2005-09-01

    Rhythmic structure is a common property of many environmental sounds including speech. Here, perceptual effects of preceding rhythmic context are assessed in experiments employing edited words for which perceived stress/syllabicity are assessed. A series of edited naturally spoken words varying perceptually from ``polite'' to ``plight,'' was created by deleting initial-vowel glottal pulses from a recording of ``polite.'' Words were identified following nonspeech precursor sequences having either trochaic (strong-weak) or iambic (weak-strong) rhythmic patterns. Precursors consisted of a harmonic spectrum (-6-dB/octave slope) filtered by four sinusoidally modulated single-pole filters. Trochaic (strong-weak) and iambic (weak-strong) rhythmic patterns were created by varying amplitude, pitch, and duration in successive segments (akin to beats) of the precursors. Precursors were comprised of two to six repetitions of these patterns. Following trochaic precursors, listeners were more likely to report hearing ``polite'' (iambic). This pattern of results indicates that perception did not assimilate to precursor pattern, consistent with rhythmic expectancy. Instead, perception shifted in a way that contrasts with precursor temporal pattern. Additional results with precursors that are more and less like speech are being conducted to further understand how auditory perception adjusts for temporal and spectral regularities. [Work supported by NIDCD.

  3. Experimental analysis of precursors to severe problem behavior.

    PubMed

    Fritz, Jennifer N; Iwata, Brian A; Hammond, Jennifer L; Bloom, Sarah E

    2013-01-01

    Some individuals engage in both mild and severe forms of problem behavior. Research has shown that when mild behaviors precede severe behaviors (i.e., the mild behaviors serve as precursors), they can (a) be maintained by the same source of reinforcement as severe behavior and (b) reduce rates of severe behavior observed during assessment. In Study 1, we developed an objective checklist to identify precursors via videotaped trials for 16 subjects who engaged in problem behavior and identified at least 1 precursor for every subject. In Study 2, we conducted separate functional analyses of precursor and severe problem behaviors for 8 subjects, and obtained correspondence between outcomes in 7 cases. In Study 3, we evaluated noncontingent reinforcement schedule thinning plus differential reinforcement of alternative behavior to reduce precursors, increase appropriate behavior, and maintain low rates of severe behavior during 3 treatment analyses for 2 subjects. Results showed that this treatment strategy was effective for behaviors maintained by positive and negative reinforcement.

  4. Precursor of kunitz trypsin inhibitor in soybean seeds

    SciTech Connect

    McGrain, A.; Chen, J.; Tan-Wilson, A. )

    1990-05-01

    Kunitz soybean trypsin inhibitor (KSTI) appears to be synthesized in precursor form which is converted by proteolytic digestion to the mature form of KSTI. Two forms of anti-cross-reacting material are evident when Western blots of extracts of developing seeds are analyzed. The precursor form increases to maximum levels as seed lengths increase to 11 mm. As the seed matures to 13 mm and turns yellow, precursor levels decrease while mature KSTI levels increase. The conversion of precursor to mature form could be demonstrated in vitro in seed extracts. The conversion could also be demonstrated in excised seeds pulse-labeled with ({sup 14}C)-leucine as loss of radioactivity from the precursor and appearance in the mature KSTI form.

  5. KIC 9832227: a red nova precursor

    NASA Astrophysics Data System (ADS)

    Molnar, Lawrence A.; Van Noord, Daniel; Kinemuchi, Karen; Smolinski, Jason P.; Alexander, Cara E.; Kobulnicky, Henry A.; Cook, Evan M.; Jang, Byoungchan; Steenwyk, Steven D.

    2017-01-01

    Molnar et al. (2015) suggested that KIC 9832227 is a contact binary star in its final years before merging and producing a red nova eruption. Analysis of light curves spanning 1999 to 2014 showed a negative time derivative and second derivative of the orbital period. The timing data were found to be well fit by the empirical exponential formula that Tylenda et al. (2011) used to describe preoutburst data of V1309 Sco. While it could not be concluded that this was the correct interpretation of the data, the prediction made for the near future was specific and falsifiable. We will present light curve data from 2015-2016 which is consistent with the extrapolation of the previous fit. As predicted, the period derivative now exceeds the range measured for other contact systems. Reanalysis of the Kepler spacecraft timing data shows a low amplitude modulation consistent with a third star with an orbital period of 1.7 y and msin i = 0.11 solar masses. We will also present spectroscopic data that show the signature of both binary components. These data rule out the presence of any additional main sequence stars with mass greater than 0.4 solar masses. Based on an updated fit to the exponential formula, we now estimate the time of merger to be the year 2022.2 with a random uncertainty of 0.6 years. These results greatly strengthen the original suggestion. The system presents an unprecedented opportunity to study the mechanism of stellar merger through targeted observations of a precursor. Molnar, L. et al. (2015), AAS Meeting #225, id.415.05. Tylenda, R., et al. (2011), AA, 528, A114.

  6. The reliability of radon as seismic precursor

    NASA Astrophysics Data System (ADS)

    Emilian Toader, Victorin; Moldovan, Iren Adelina; Ionescu, Constantin; Marmureanu, Alexandru

    2016-04-01

    Our multidisciplinary network (AeroSolSys) located in Vrancea (Curvature Carpathian Mountains) includes radon concentration monitoring in five stations. We focus on lithosphere and near surface low atmosphere phenomena using real-time information about seismicity, + / - ions, clouds, solar radiation, temperature (air, ground), humidity, atmospheric pressure, wind speed and direction, telluric currents, variations of the local magnetic field, infrasound, variations of the atmospheric electrostatic field, variations in the earth crust with inclinometers, electromagnetic activity, CO2 concentration, ULF radio wave propagation, seismo-acoustic emission, animal behavior. The main purpose is to inform the authorities about risk situation and update hazard scenarios. The radon concentration monitoring is continuously with 1 hour or 3 hours sample rate in locations near to faults in an active seismic zone characterized by intermediate depth earthquakes. Trigger algorithms include standard deviation, mean and derivative methods. We correlate radon concentration measurements with humidity, temperature and atmospheric pressure from the same equipment. In few stations we have meteorological information, too. Sometime the radon concentration has very high variations (maxim 4535 Bq/m3 from 106 Bq/m3) in short time (1 - 2 days) without being accompanied by an important earthquake. Generally the cause is the high humidity that could be generated by tectonic stress. Correlation with seismicity needs information from minimum 6 month in our case. For 10605 hours, 618 earthquakes with maxim magnitude 4.9 R, we have got radon average 38 Bq/m3 and exposure 408111 Bqh/m3 in one station. In two cases we have correlation between seismicity and radon concentration. In other one we recorded high variation because the location was in an area with multiple faults and a river. Radon can be a seismic precursor but only in a multidisciplinary network. The anomalies for short or long period of

  7. Precursor Science for the Terrestrial Planet Finder

    NASA Technical Reports Server (NTRS)

    Lawson, P. R. (Editor); Unwin, S. C. (Editor); Beichman, C. A. (Editor)

    2004-01-01

    This document outlines a path for the development of the field of extrasolar planet research, with a particular emphasis on the goals of the Terrestrial Planet Finder (TPF). Over the past decade, a new field of research has developed, the study of extrasolar planetary systems, driven by the discovery of massive planets around nearby stars. The planet count now stands at over 130. Are there Earth-like planets around nearby stars? Might any of those planets be conducive to the formation and maintenance of life? These arc the questions that TPF seeks to answer. TPF will be implemented as a suite of two space observatories, a 6-m class optical coronagraph, to be launched around 20 14, and a formation flying mid-infrared interferometer, to be launched sometime prior to 2020. These facilities will survey up to 165 or more nearby stars and detect planets like Earth should they be present in the 'habitable zone' around each star. With observations over a broad wavelength range, TPF will provide a robust determination of the atmospheric composition of planets to assess habitability and the presence of life. At this early stage of TPF's development, precursor observational and theoretical programs are essential to help define the mission, to aid our understanding of the planets that TPF could discover, and to characterize the stars that TPF will eventually study. This document is necessarily broad in scope because the significance of individual discoveries is greatly enhanced when viewed in thc context of the field as a whole. This document has the ambitious goal of taking us from our limited knowledge today, in 2004, to the era of TPF observations in the middle of the next decade. We must use the intervening years wisely. This document will be reviewed annually and updated as needed. The most recent edition is available online at http://tpf.jpl.nasa.gov/ or by email request to lawson@hucy.jpl.nasa.gov

  8. PRECOMBUSTION REMOVAL OF HAZARDOUS AIR POLLUTANT PRECURSORS

    SciTech Connect

    Unknown

    2000-10-09

    In response to growing environmental concerns reflected in the 1990 Clean Air Act Amendment (CAAA), the United States Department of Energy (DOE) sponsored several research and development projects in late 1995 as part of an initiative entitled Advanced Environmental Control Technologies for Coal-Based Power Systems. The program provided cost-shared support for research and development projects that could accelerate the commercialization of affordable, high-efficiency, low-emission, coal-fueled electric generating technologies. Clean coal technologies developed under this program would serve as prototypes for later generations of technologies to be implemented in the industrial sector. In order to identify technologies with the greatest potential for commercial implementation, projects funded under Phase I of this program were subject to competitive review by DOE before being considered for continuation funding under Phase II. One of the primary topical areas identified under the DOE initiative relates to the development of improved technologies for reducing the emissions of air toxics. Previous studies have suggested that many of the potentially hazardous air pollutant precursors (HAPPs) occur as trace elements in the mineral matter of run-of-mine coals. As a result, these elements have the potential to be removed prior to combustion at the mine site by physical coal cleaning processes (i.e., coal preparation). Unfortunately, existing coal preparation plants are generally limited in their ability to remove HAPPs due to incomplete liberation of the mineral matter and high organic associations of some trace elements. In addition, existing physical coal cleaning plants are not specifically designed or optimized to ensure that high trace element rejections may be achieved.

  9. Doublecortin in Oligodendrocyte Precursor Cells in the Adult Mouse Brain

    PubMed Central

    Boulanger, Jenna J.; Messier, Claude

    2017-01-01

    Key Points Oligodendrocyte precursor cells express doublecortin, a microtubule-associated protein.Oligodendrocyte precursor cells express doublecortin, but at a lower level of expression than in neuronal precursor.Doublecortin is not associated with a potential immature neuronal phenotype in Oligodendrocyte precursor cells. Oligodendrocyte precursor cells (OPC) are glial cells that differentiate into myelinating oligodendrocytes during embryogenesis and early stages of post-natal life. OPCs continue to divide throughout adulthood and some eventually differentiate into oligodendrocytes in response to demyelinating lesions. There is growing evidence that OPCs are also involved in activity-driven de novo myelination of previously unmyelinated axons and myelin remodeling in adulthood. Considering these roles in the adult brain, OPCs are likely mobile cells that can migrate on some distances before they differentiate into myelinating oligodendrocytes. A number of studies have noted that OPCs express doublecortin (DCX), a microtubule-associated protein expressed in neural precursor cells and in migrating immature neurons. Here we describe the distribution of DCX in OPCs. We found that almost all OPCs express DCX, but the level of expression appears to be much lower than what is found in neural precursor. We found that DCX is downregulated when OPCs start expressing mature oligodendrocyte markers and is absent in myelinating oligodendrocytes. DCX does not appear to signal an immature neuronal phenotype in OPCs in the adult mouse brain. Rather, it could be involved either in cell migration, or as a marker of an immature oligodendroglial cell phenotype.

  10. Dopamine depletion impairs precursor cell proliferation in Parkinson disease.

    PubMed

    Höglinger, Günter U; Rizk, Pamela; Muriel, Marie P; Duyckaerts, Charles; Oertel, Wolfgang H; Caille, Isabelle; Hirsch, Etienne C

    2004-07-01

    Cerebral dopamine depletion is the hallmark of Parkinson disease. Because dopamine modulates ontogenetic neurogenesis, depletion of dopamine might affect neural precursors in the subependymal zone and subgranular zone of the adult brain. Here we provide ultrastructural evidence showing that highly proliferative precursors in the adult subependymal zone express dopamine receptors and receive dopaminergic afferents. Experimental depletion of dopamine in rodents decreases precursor cell proliferation in both the subependymal zone and the subgranular zone. Proliferation is restored completely by a selective agonist of D2-like (D2L) receptors. Experiments with neural precursors from the adult subependymal zone grown as neurosphere cultures confirm that activation of D2L receptors directly increases the proliferation of these precursors. Consistently, the numbers of proliferating cells in the subependymal zone and neural precursor cells in the subgranular zone and olfactory bulb are reduced in postmortem brains of individuals with Parkinson disease. These observations suggest that the generation of neural precursor cells is impaired in Parkinson disease as a consequence of dopaminergic denervation.

  11. PHOTOSPHERIC RADIUS EXPANSION IN SUPERBURST PRECURSORS FROM NEUTRON STARS

    SciTech Connect

    Keek, L.

    2012-09-10

    Thermonuclear runaway burning of carbon is in rare cases observed from accreting neutron stars as day-long X-ray flares called superbursts. In the few cases where the onset is observed, superbursts exhibit a short precursor burst at the start. In each instance, however, the data are of insufficient quality for spectral analysis of the precursor. Using data from the propane anti-coincidence detector of the Proportional Counter Array instrument on the Rossi X-ray Timing Explorer, we perform the first detailed time-resolved spectroscopy of precursors. For a superburst from 4U 1820-30 we demonstrate the presence of photospheric radius expansion. We find the precursor to be 1.4-2 times more energetic than other short bursts from this source, indicating that the burning of accreted helium is insufficient to explain the full precursor. Shock heating would be able to account for the shortfall in energy. We argue that this precursor is a strong indication that the superburst starts as a detonation, and that a shock induces the precursor. Furthermore, we employ our technique to study the superexpansion phase of the same superburst in greater detail.

  12. Methods for forming particles from single source precursors

    DOEpatents

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua

    2011-08-23

    Single source precursors are subjected to carbon dioxide to form particles of material. The carbon dioxide may be in a supercritical state. Single source precursors also may be subjected to supercritical fluids other than supercritical carbon dioxide to form particles of material. The methods may be used to form nanoparticles. In some embodiments, the methods are used to form chalcopyrite materials. Devices such as, for example, semiconductor devices may be fabricated that include such particles. Methods of forming semiconductor devices include subjecting single source precursors to carbon dioxide to form particles of semiconductor material, and establishing electrical contact between the particles and an electrode.

  13. MMPM - Mars MetNet Precursor Mission

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Schmidt, W.; Pichkhadze, K.; Linkin, V.; Vazquez, L.; Uspensky, M.; Polkko, J.; Genzer, M.; Lipatov, A.; Guerrero, H.; Alexashkin, S.; Haukka, H.; Savijarvi, H.; Kauhanen, J.

    2008-09-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. Prototyping of the payload instrumentation with final dimensions was carried out in 2003-2006.This huge development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development. To understand the behavior and dynamics of the Martian atmosphere, a wealth of simultaneous in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes. This will be performed by the Mars MetNet Mission. In addition to the science aspects the

  14. Biological Indicators in Studies of Earthquake Precursors

    NASA Astrophysics Data System (ADS)

    Sidorin, A. Ya.; Deshcherevskii, A. V.

    2012-04-01

    Time series of data on variations in the electric activity (EA) of four species of weakly electric fish Gnathonemus leopoldianus and moving activity (MA) of two cat-fishes Hoplosternum thoracatum and two groups of Columbian cockroaches Blaberus craniifer were analyzed. The observations were carried out in the Garm region of Tajikistan within the frameworks of the experiments aimed at searching for earthquake precursors. An automatic recording system continuously recorded EA and DA over a period of several years. Hourly means EA and MA values were processed. Approximately 100 different parameters were calculated on the basis of six initial EA and MA time series, which characterize different variations in the EA and DA structure: amplitude of the signal and fluctuations of activity, parameters of diurnal rhythms, correlated changes in the activity of various biological indicators, and others. A detailed analysis of the statistical structure of the total array of parametric time series obtained in the experiment showed that the behavior of all animals shows a strong temporal variability. All calculated parameters are unstable and subject to frequent changes. A comparison of the data obtained with seismicity allow us to make the following conclusions: (1) The structure of variations in the studied parameters is represented by flicker noise or even a more complex process with permanent changes in its characteristics. Significant statistics are required to prove the cause-and-effect relationship of the specific features of such time series with seismicity. (2) The calculation of the reconstruction statistics in the EA and MA series structure demonstrated an increase in their frequency in the last hours or a few days before the earthquake if the hypocenter distance is comparable to the source size. Sufficiently dramatic anomalies in the behavior of catfishes and cockroaches (changes in the amplitude of activity variation, distortions of diurnal rhythms, increase in the

  15. BEHAVIORAL RISK DISPARITIES IN A RANDOM SAMPLE OF SELF-IDENTIFYING GAY AND NON-GAY MALE UNIVERSITY STUDENTS

    PubMed Central

    Rhodes, Scott D.; McCoy, Thomas P.; Wilkin, Aimee M.; Wolfson, Mark

    2013-01-01

    This internet-based study was designed to compare health risk behaviors of gay and non-gay university students from stratified random cross-sectional samples of undergraduate students. Mean age of the 4,167 male participants was 20.5 (±2.7) years. Of these, 206 (4.9%) self-identified as gay and 3,961 (95.1%) self-identified as heterosexual. After adjusting for selected characteristics and clustering within university, gay men had higher odds of reporting: multiple sexual partners; cigarette smoking; methamphetamine use; gamma-hydroxybutyrate (GHB) use; other illicit drug use within the past 30 days and during lifetime; and intimate partner violence (IPV). Understanding the health risk behaviors of gay and heterosexual men is crucial to identifying associated factors and intervening upon them using appropriate and tailored strategies to reduce behavioral risk disparities and improve health outcomes. PMID:19882428

  16. Review: Drug concentrations in hair and their relevance in drug facilitated crimes.

    PubMed

    Xiang, Ping; Shen, Min; Drummer, Olaf H

    2015-11-01

    Segmental hair analysis can provide valuable retrospective information on the history of drug exposure in victims of drug facilitated crimes (DFC). This is now possible with availability of sensitive tandem MS techniques such as GC-MS/MS and LC-MS/MS allowing drugs to be detected at pg/mg concentrations after a single dose. In this review hair concentrations of 35 psychoactive drugs given in 20 controlled dose studies are reviewed and compared to the 25 different drugs detected in reported case work. The most common drugs were the benzodiazepines and related hypnotics, gamma-hydroxybutyrate (GHB), ketamine and methamphetamine. Those concentrations reported in DFC were mostly similar or higher than that seen in controlled dose studies. The factors that affecting interpretation of segmental hair results including hair color, growth rates, sample preparation and surface contamination are discussed.

  17. [Drug facilitated sexual assault].

    PubMed

    Alempijević, Djordje; Savić, Slobodan; Stojanović, Jovan; Spasić, Andjelka

    2007-01-01

    In line with the fact that there is little information regarding drug facilitated sexual assault in national medical literature, the authors aimed to prepare a review of the phenomenon based on available international references. Therefore we offered a definition of the concept of sexual assault, and rape in particular. Consent and ability for valid consent for sexual intercourse were defined as well. A review contains discussion about the basic elements of a concept of drug-facilitated sexual assault. There is also available information in regard to pharmacology of common data rape drugs, i.e. flunitrazepam, gamma-hydroxybutyrate (GHB), and ketamine. We indicate the utmost importance of prompt collecting of biological samples for toxicological screening in patients who are suspected victims of drug facilitated sexual assault.

  18. Drug-facilitated sexual assault ('date rape').

    PubMed

    Schwartz, R H; Milteer, R; LeBeau, M A

    2000-06-01

    In the past few years, drug-facilitated sexual assaults have received widespread media coverage. In addition to alcohol, the most frequently used date-rape drug, flunitrazepam (Rohypnol), a fast-acting benzodiazepine, and gamma-hydroxybutyrate (GHB) and its congeners are among the most popular drugs used for this purpose. The latter drug is easily procured at some gymnasiums, popular bars, discos, and rave clubs, as well as over the Internet. Perpetrators choose these drugs because they act rapidly, produce disinhibition and relaxation of voluntary muscles, and cause the victim to have lasting anterograde amnesia for events that occur under the influence of the drug. Alcoholic beverages potentiate the drug effects. We review several date-rape drugs, provide information on laboratory testing for them, and offer guidelines for preventing drug-facilitated sexual assault.

  19. Analytical developments in toxicological investigation of drug-facilitated sexual assault.

    PubMed

    Negrusz, Adam; Gaensslen, R E

    2003-08-01

    This paper gives a general overview of the drug-facilitated sexual assault phenomenon. Sexual assault perpetrated on both women and men, while incapacitated by so-called date-rape drugs, recently became the focus of many investigations conducted by law enforcement agencies in the US throughout the 1990s; an alarming increase in reports of this crime as well as in the number of scientific publications on drug-facilitated sexual assault has been observed. The list of drugs reportedly associated with sexual assault is long and among others includes flunitrazepam with other benzodiazepines such as diazepam, temazepam, clonazepam, oxazepam, as well as gamma-hydroxybutyrate (GHB), ketamine, and scopolamine. We discuss the most recent analytical developments in the toxicological investigation of drug-facilitated rape designed to reveal drug presence and that may help successfully prosecute perpetrators.

  20. Raves: a review of the culture, the drugs and the prevention of harm

    PubMed Central

    Weir, E

    2000-01-01

    Raves are all-night dance parties attended by large numbers of youth, sometimes in excess of 20,000. The rave scene, which is international in scope, is distinguished by clandestine venues, hypnotic electronic music and the liberal use of drugs such as ecstasy (3,4-methylenedioxymethamphetamine), GHB (gamma-hydroxybutyrate) and ketamine. Several rave-related deaths in Canada in 1999 alerted health authorities, parents and police to the health risks of rave attendance. Family physicians, emergency physicians and pediatricians should have some understanding of raves, the drugs and the health risks so they can effectively counsel and treat patients. The rave culture in Canada and the drugs commonly used at raves are reviewed, and strategies and initiatives for harm reduction are discussed. PMID:10906922

  1. Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition And Treatment.

    PubMed

    Santos, Cynthia; Olmedo, Ruben E

    2017-03-01

    Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms.

  2. Precursor composites for oxygen dispersion hardened silver sheathed superconductor composites

    DOEpatents

    Podtburg, E.R.

    1999-06-22

    An oxide superconductor composite having improved texture and durability is disclosed. The oxide superconductor composite includes an oxide superconductor phase substantially surrounded with/by a noble metal matrix, the noble metal matrix comprising a metal oxide in an amount effective to form metal oxide domains that increase hardness of the composite. The composite is characterized by a degree of texture at least 10% greater than a comparable oxide superconductor composite lacking metal oxide domains. An oxide superconducting composite may be prepared by oxidizing the precursor composite under conditions effective to form solute metal oxide domains within the silver matrix and to form a precursor oxide in the precursor alloy phase; subjecting the oxidized composite to a softening anneal under conditions effective to relieve stress within the noble metal phase; and converting the oxide precursor into an oxide superconductor. 1 fig.

  3. Precursor composites for oxygen dispersion hardened silver sheathed superconductor composites

    DOEpatents

    Podtburg, Eric R.

    1999-01-01

    An oxide superconductor composite having improved texture and durability. The oxide superconductor composite includes an oxide superconductor phase substantially surrounded with/by a noble metal matrix, the noble metal matrix comprising a metal oxide in an amount effective to form metal oxide domains that increase hardness of the composite. The composite is characterized by a degree of texture at least 10% greater than a comparable oxide superconductor composite lacking metal oxide domains. An oxide superconducting composite may be prepared by oxidizing the precursor composite under conditions effective to form solute metal oxide domains within the silver matrix and to form a precursor oxide in the precursor alloy phase; subjecting the oxidized composite to a softening anneal under conditions effective to relieve stress within the noble metal phase; and converting the oxide precursor into an oxide superconductor.

  4. Quarternary Amines as Nitrosamine Precursors: A Role for Consumer Products?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitrosamine formation is associated with wastewater-impacted water supplies, but the specific precursors within municipal wastewater effluents have not been identified. Quaternary amines are significant constituents of consumer products, including shampoos, detergents and fabric softeners. Experimen...

  5. Liquid precursor for deposition of copper selenide and method of preparing the same

    DOEpatents

    Curtis, Calvin J.; Miedaner, Alexander; Franciscus Antonius Maria Van Hest, Marinus; Ginley, David S.; Hersh, Peter A.; Eldada, Louay; Stanbery, Billy J.

    2015-09-08

    Liquid precursors containing copper and selenium suitable for deposition on a substrate to form thin films suitable for semiconductor applications are disclosed. Methods of preparing such liquid precursors and methods of depositing a precursor on a substrate are also disclosed.

  6. Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase.

    PubMed

    Hogema, B M; Gupta, M; Senephansiri, H; Burlingame, T G; Taylor, M; Jakobs, C; Schutgens, R B; Froestl, W; Snead, O C; Diaz-Arrastia, R; Bottiglieri, T; Grompe, M; Gibson, K M

    2001-10-01

    Succinate semialdehyde dehydrogenase (ALDH5A1, encoding SSADH deficiency is a defect of 4-aminobutyric acid (GABA) degradation that manifests in humans as 4-hydroxybutyric (gamma-hydroxybutyric, GHB) aciduria. It is characterized by a non-specific neurological disorder including psychomotor retardation, language delay, seizures, hypotonia and ataxia. The current therapy, vigabatrin (VGB), is not uniformly successful. Here we report the development of Aldh5a1-deficient mice. At postnatal day 16-22 Aldh5a1-/- mice display ataxia and develop generalized seizures leading to rapid death. We observed increased amounts of GHB and total GABA in urine, brain and liver homogenates and detected significant gliosis in the hippocampus of Aldh5a1-/- mice. We found therapeutic intervention with phenobarbital or phenytoin ineffective, whereas intervention with vigabatrin or the GABAB receptor antagonist CGP 35348 (ref. 2) prevented tonic-clonic convulsions and significantly enhanced survival of the mutant mice. Because neurologic deterioration coincided with weaning, we hypothesized the presence of a protective compound in breast milk. Indeed, treatment of mutant mice with the amino acid taurine rescued Aldh5a1-/- mice. These findings provide insight into pathomechanisms and may have therapeutic relevance for the human SSADH deficiency disease and GHB overdose and toxicity.

  7. Improved Single-Source Precursors for Solar-Cell Absorbers

    NASA Technical Reports Server (NTRS)

    Banger, Kulbinder K.; Harris, Jerry; Hepp, Aloysius

    2007-01-01

    Improved single-source precursor compounds have been invented for use in spray chemical vapor deposition (spray CVD) of chalcopyrite semiconductor absorber layers of thin-film cells. A "single-source precursor compound" is a single molecular compound that contains all the required elements, which when used under the spray CVD conditions, thermally decomposes to form CuIn(x)Ga(1-x)S(y)Se(2-y).

  8. Differential properties of dentate gyrus and CA1 neural precursors.

    PubMed

    Becq, H; Jorquera, I; Ben-Ari, Y; Weiss, S; Represa, A

    2005-02-05

    In the present article we investigated the properties of CA1 and dentate gyrus cell precursors in adult rodents both in vivo and in vitro. Cell proliferation in situ was investigated by rating the number of cells incorporating BrdU after kainate-induced seizures. CA1 precursors displayed a greater proliferation capacity than dentate gyrus precursors. The majority of BrdU-labeled cells in CA1 expressed Nestin and Mash-1, two markers of neural precursors. BrdU-positive cells in the dentate gyrus expressed Nestin, but only a few expressed Mash-1. In animals pretreated with the antimitotic azacytidine, the capacity of kainate to enhance the proliferation was higher in CA1 than in the dentate gyrus. Differences in intrinsic progenitor cell activity could underlie these different expansion capacities. Thus, we compared the renewal- expansion and multipotency of dentate gyrus and CA1 precursors isolated in vitro. We found that the dissected CA1 region, including the periventricular zone, is enriched in neurosphere-forming cells (presumed stem cells), which respond to either EGF or FGF-2. Dentate gyrus contains fewer neurosphere-forming cells and none that respond to FGF-2 alone. Neurospheres generated from CA1 were multipotent and produced neurons, astrocytes, and oligodendrocytes, while dentate gyrus neurospheres mostly produced glial cells. The analysis of the effects of EGF on organotypic cultures of hippocampal slices depicted similar features: BrdU and Nestin immunoreactivities increased after EGF treatment in CA1 but not in the dentate gyrus. These results suggest that CA1 precursors are more stem-cell-like than granule cell precursors, which may represent a more restricted precursor cell.

  9. Tall oil precursors in the sapwood of four southern pines

    SciTech Connect

    Zinkel, D.F.; Foster, D.O.

    1980-05-01

    The composition of the tall oil precursors in the sapwood of slash, longleaf, shortleaf, and Virginia pines has been determined. Qualitative and quantitative changes occur in these precursors during kraft pulping. In addition to isomerization of fatty acids and resin acids, significant losses of resin acids occur. These losses are of economic significance in tall oil recovery, particularly in potential future recovery of lightwood resin acids (rosin) as tall oil.

  10. SEARCH FOR PRECURSOR ERUPTIONS AMONG TYPE IIB SUPERNOVAE

    SciTech Connect

    Strotjohann, Nora L.; Ofek, Eran O.; Gal-Yam, Avishay; Yaron, Ofer; Sullivan, Mark; Kulkarni, Shrinivas R.; Cao, Yi; Shaviv, Nir J.; Fremling, Christoffer; Sollerman, Jesper; Kasliwal, Mansi M.; Nugent, Peter E.; Arcavi, Iair; Filippenko, Alexei V.; Laher, Russ; Surace, Jason

    2015-10-01

    The progenitor stars of several Type IIb supernovae (SNe) show indications of extended hydrogen envelopes. These envelopes might be the outcome of luminous energetic pre-explosion events, so-called precursor eruptions. We use the Palomar Transient Factory (PTF) pre-explosion observations of a sample of 27 nearby SNe IIb to look for such precursors during the final years prior to the SN explosion. No precursors are found when combining the observations in 15-day bins, and we calculate the absolute-magnitude-dependent upper limit on the precursor rate. At the 90% confidence level, SNe IIb have on average <0.86 precursors as bright as an absolute R-band magnitude of −14 in the final 3.5 years before the explosion and <0.56 events over the final year. In contrast, precursors among SNe IIn have a ≳5 times higher rate. The kinetic energy required to unbind a low-mass stellar envelope is comparable to the radiated energy of a few-weeks-long precursor that would be detectable for the closest SNe in our sample. Therefore, mass ejections, if they are common in such SNe, are radiatively inefficient or have durations longer than months. Indeed, when using 60-day bins, a faint precursor candidate is detected prior to SN 2012cs (∼2% false-alarm probability). We also report the detection of the progenitor of SN 2011dh that does not show detectable variability over the final two years before the explosion. The suggested progenitor of SN 2012P is still present, and hence is likely a compact star cluster or an unrelated object.

  11. Elements of the tsunami precursors' detection physics

    NASA Astrophysics Data System (ADS)

    Novik, Oleg; Ruzhin, Yuri; Ershov, Sergey; Volgin, Max; Smirnov, Fedor

    ionosphere from the buoy, balloon and satellite complexes. The balloon and buoy complexes will transmit data to a shore station over satellite link. The frequency ranges and sensitivity thresholds of all of the sensors of the LOAMS will be adapted to the characteristics of expected seismic signals according to the numerical research above. Computational methods and statistical analysis (e.g. seismic changes of coherence of spatially distributed sensors of different nature) of the recorded multidimensional time series will be used for prognostic interpretation. The multilevel recordings will provide a stable noise (e.g. ionosphere Pc pulsations, hard sea, industry) and seismic event detection. An intensive heat flow typical for tectonically active lithosphere zones may be considered as an energy source for advanced modifications of the LOAMS. The latter may be used as a warning system for continental and marine technologies, e.g. a sea bottom geothermal energy production. Indeed, seismic distraction of the nuclear power station Fukushima I demonstrates that similar technology hardly is able to solve the energy problems in seismically active regions. On the other hand, the LOAMS may be considered as a scientific observatory for development of the seaquake/tsunami precursor physics, i.e. seismo-hydro-electromagnetics.

  12. Risk Assessment of Infrastructure System of Systems with Precursor Analysis.

    PubMed

    Guo, Zhenyu; Haimes, Yacov Y

    2016-08-01

    Physical infrastructure systems are commonly composed of interconnected and interdependent subsystems, which in their essence constitute system of systems (S-o-S). System owners and policy researchers need tools to foresee potential emergent forced changes and to understand their impact so that effective risk management strategies can be developed. We develop a systemic framework for precursor analysis to support the design of an effective and efficient precursor monitoring and decision support system with the ability to (i) identify and prioritize indicators of evolving risks of system failure; and (ii) evaluate uncertainties in precursor analysis to support informed and rational decision making. This integrated precursor analysis framework is comprised of three processes: precursor identification, prioritization, and evaluation. We use an example of a highway bridge S-o-S to demonstrate the theories and methodologies of the framework. Bridge maintenance processes involve many interconnected and interdependent functional subsystems and decision-making entities and bridge failure can have broad social and economic consequences. The precursor analysis framework, which constitutes an essential part of risk analysis, examines the impact of various bridge inspection and maintenance scenarios. It enables policy researchers and analysts who are seeking a risk perspective on bridge infrastructure in a policy setting to develop more risk informed policies and create guidelines to efficiently allocate limited risk management resources and mitigate severe consequences resulting from bridge failures.

  13. Rb suppresses human cone-precursor-derived retinoblastoma tumours.

    PubMed

    Xu, Xiaoliang L; Singh, Hardeep P; Wang, Lu; Qi, Dong-Lai; Poulos, Bradford K; Abramson, David H; Jhanwar, Suresh C; Cobrinik, David

    2014-10-16

    Retinoblastoma is a childhood retinal tumour that initiates in response to biallelic RB1 inactivation and loss of functional retinoblastoma (Rb) protein. Although Rb has diverse tumour-suppressor functions and is inactivated in many cancers, germline RB1 mutations predispose to retinoblastoma far more strongly than to other malignancies. This tropism suggests that retinal cell-type-specific circuitry sensitizes to Rb loss, yet the nature of the circuitry and the cell type in which it operates have been unclear. Here we show that post-mitotic human cone precursors are uniquely sensitive to Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations and in intact retina. Proliferation followed the induction of E2F-regulated genes, and depended on factors having strong expression in maturing cone precursors and crucial roles in retinoblastoma cell proliferation, including MYCN and MDM2. Proliferation of Rb-depleted cones and retinoblastoma cells also depended on the Rb-related protein p107, SKP2, and a p27 downregulation associated with cone precursor maturation. Moreover, Rb-depleted cone precursors formed tumours in orthotopic xenografts with histological features and protein expression typical of human retinoblastoma. These findings provide a compelling molecular rationale for a cone precursor origin of retinoblastoma. More generally, they demonstrate that cell-type-specific circuitry can collaborate with an initiating oncogenic mutation to enable tumorigenesis.

  14. Role of neural precursor cells in promoting repair following stroke

    PubMed Central

    Dibajnia, Pooya; Morshead, Cindi M

    2013-01-01

    Stem cell-based therapies for the treatment of stroke have received considerable attention. Two broad approaches to stem cell-based therapies have been taken: the transplantation of exogenous stem cells, and the activation of endogenous neural stem and progenitor cells (together termed neural precursors). Studies examining the transplantation of exogenous cells have demonstrated that neural stem and progenitor cells lead to the most clinically promising results. Endogenous activation of neural precursors has also been explored based on the fact that resident precursor cells have the inherent capacity to proliferate, migrate and differentiate into mature neurons in the uninjured adult brain. Studies have revealed that these neural precursor cell behaviours can be activated following stroke, whereby neural precursors will expand in number, migrate to the infarct site and differentiate into neurons. However, this innate response is insufficient to lead to functional recovery, making it necessary to enhance the activation of endogenous precursors to promote tissue repair and functional recovery. Herein we will discuss the current state of the stem cell-based approaches with a focus on endogenous repair to treat the stroke injured brain. PMID:23064725

  15. Anti-Alcohol and Anxiolytic Properties of a New Chemical Entity, GET73

    PubMed Central

    Loche, Antonella; Simonetti, Francesco; Lobina, Carla; Carai, Mauro A. M.; Colombo, Giancarlo; Castelli, M. Paola; Barone, Domenico; Cacciaglia, Roberto

    2012-01-01

    N-[(4-trifluoromethyl)benzyl]4-methoxybutyramide (GET73) is a newly synthesized compound structurally related to the clinically used, alcohol-substituting agent, gamma-hydroxybutyric acid (GHB). The present study was designed to assess whether GET73 may share with GHB the capacity to reduce alcohol intake in rats. Additionally, the effect of treatment with GET73 on anxiety-related behaviors and cognitive tasks in rats was investigated. A series of in vitro binding assays investigated the capacity of GET73 to bind to the GHB binding site and multiple other receptors. GET73 (10−9–10−3 M) failed to inhibit [3H]GHB binding at both high- and low-affinity GHB recognition sites in rat cortical membranes. GET73 displayed minimal, if any, binding at dopamine, serotonin, GABA, and glutamate receptors in membranes from different rat brain areas. Acute treatment with low-to-moderate, non-sedative doses of GET73 (5–50 mg/kg, i.g. or i.p.) (a) reduced alcohol intake and suppressed “alcohol deprivation effect” (a model of alcohol relapse) in selectively bred, Sardinian alcohol-preferring (sP) rats, (b) exerted anxiolytic effects in Sprague-Dawley (SD) and sP rats exposed to the Elevated Plus Maze test, and (c) tended to induce promnestic effects in SD rats exposed to a modified water version of the Hebb–Williams maze test. Although the mechanism of GET73 action is currently unknown, the results of the present study suggest that GET73 has a multifaceted pharmacological profile, including the capacity to reduce alcohol drinking and anxiety-related behaviors in rats. PMID:22347868

  16. Predicting Solar Cycle 24 Using a Geomagnetic Precursor Pair

    NASA Technical Reports Server (NTRS)

    Pesnell, W. Dean

    2014-01-01

    We describe using Ap and F(10.7) as a geomagnetic-precursor pair to predict the amplitude of Solar Cycle 24. The precursor is created by using F(10.7) to remove the direct solar-activity component of Ap. Four peaks are seen in the precursor function during the decline of Solar Cycle 23. A recurrence index that is generated by a local correlation of Ap is then used to determine which peak is the correct precursor. The earliest peak is the most prominent but coincides with high levels of non-recurrent solar activity associated with the intense solar activity of October and November 2003. The second and third peaks coincide with some recurrent activity on the Sun and show that a weak cycle precursor closely following a period of strong solar activity may be difficult to resolve. A fourth peak, which appears in early 2008 and has recurrent activity similar to precursors of earlier solar cycles, appears to be the "true" precursor peak for Solar Cycle 24 and predicts the smallest amplitude for Solar Cycle 24. To determine the timing of peak activity it is noted that the average time between the precursor peak and the following maximum is approximately equal to 6.4 years. Hence, Solar Cycle 24 would peak during 2014. Several effects contribute to the smaller prediction when compared with other geomagnetic-precursor predictions. During Solar Cycle 23 the correlation between sunspot number and F(10.7) shows that F(10.7) is higher than the equivalent sunspot number over most of the cycle, implying that the sunspot number underestimates the solar-activity component described by F(10.7). During 2003 the correlation between aa and Ap shows that aa is 10 % higher than the value predicted from Ap, leading to an overestimate of the aa precursor for that year. However, the most important difference is the lack of recurrent activity in the first three peaks and the presence of significant recurrent activity in the fourth. While the prediction is for an amplitude of Solar Cycle 24 of

  17. Alkoxide-based precursors for direct electrospinning of alumina fibers

    NASA Astrophysics Data System (ADS)

    Maneeratana, Vasana

    The vision for space exploration in 2004 reinvigorated excitement that was engendered during the 1960's space race. Looking to assist NASA's agency wide mission to develop new technologies to enhance space travel, it is the ultimate goal of this work to support future missions with a hand-held electrospinning apparatus to instantaneously repair existing crucial ceramic fiber structures, such as spacesuits, insulative foams, and tiles. In this research, a new type of precursor is designed based from aluminum alkoxide-based precursors, since alumina serves as a base material for a majority of high-temperature applications. The structure-processing behavior of these precursors is subsequently studied. New precursors of aluminum alkoxides were prepared by modifying solutions; as a result various types of structures were produced, ranging from continuous hollow fibers, continuous solid fibers, or hollow particles. Direct electrospinning with these alkoxide-based precursors yielded an average of 1.9 g/hr of Al2O3, compared to literature with the highest theoretical yield calculated to be 0.68 g/hr. Further exploration of electrospinning parameters found that flow rate directly related to exposure times; therefore fibers were produced in the atmosphere through hydrolysis/condensation with simultaneous solvent evaporation. Furthermore other processing parameters, including the effect of the microstructure due to processing in an electric field were studied. It was found that electrospinning promotes the reaction of the alkoxide, which thereby reduces trapped solvents. As a result of firing schedules, the fibers' hollow features were preserved, and precursors with volatile species resulted in near net shaped fibers. At low firing temperatures, specific surface areas in the range of 330-345 m 2/g were found electrospun fibers. Additionally modified precursors lowered alpha transitions of fibers down to ˜900°C.

  18. Phosphorylation of the transit sequence of chloroplast precursor proteins.

    PubMed

    Waegemann, K; Soll, J

    1996-03-15

    A protein kinase was located in the cytosol of pea mesophyll cells. The protein kinase phosphorylates, in an ATP-dependent manner, chloroplast-destined precursor proteins but not precursor proteins, which are located to plant mitochondria or plant peroxisomes. The phosphorylation occurs on either serine or threonine residues, depending on the precursor protein used. We demonstrate the specific phosphorylation of the precursor forms of the chloroplast stroma proteins ferredoxin (preFd), small subunit of ribulose-bisphosphate-carboxylase (preSSU), the thylakoid localized light-harvesting chlorophyll a/b-binding protein (preLHCP), and the thylakoid lumen-localized proteins of the oxygen-evolving complex of 23 kDa (preOE23) and 33 kDa (preOE33). In the case of thylakoid lumen proteins which possess bipartite transit sequences, the phosphorylation occurs within the stroma-targeting domain. By using single amino acid substitution within the presequences of preSSU, preOE23, and preOE33, we were able to tentatively identify a consensus motif for the precursor protein protein kinase. This motif is (P/G)X(n)(R/K)X(n)(S/T)X(n) (S*/T*), were n = 0-3 amino acids spacer and S*/T* represents the phosphate acceptor. The precursor protein protein kinase is present only in plant extracts, e.g. wheat germ and pea, but not in a reticulocyte lysate. Protein import experiments into chloroplasts revealed that phosphorylated preSSU binds to the organelles, but dephosphorylation seems required to complete the translocation process and to obtain complete import. These results suggest that a precursor protein protein phosphatase is involved in chloroplast import and represents a so far unidentified component of the import machinery. In contrast to sucrose synthase, a cytosolic marker protein, the precursor protein protein kinase seems to adhere partially to the chloroplast surface. A phosphorylation-dephosphorylation cycle of chloroplast-destined precursor proteins might represent one step

  19. Plutonium Immobilization Project (PIP) Precursor Material Calcine Temperature

    SciTech Connect

    Cozzi, A.D.

    1999-07-29

    As a result of the end of the Cold War, approximately 50 metric tons of plutonium are no longer needed and have been identified for disposition. A ceramic waste form is the chosen option for immobilization of the excess plutonium. The plutonium ceramic form then will be encased in high-level waste glass using can-in-canister technology for final disposition. The precursor materials are the non-radioactive components that are added to the plutonium feed stream to form the desired phases in the immobilization product. The precursor materials are blended and calcined prior to being mixed with the plutonium feed stream. The purpose of the calcine step is to remove any physical or chemical water retained in the precursors and convert any hydroxides or carbonates to the oxides. Initially, a temperature of 750 degrees C for a period of one hour was chosen for the calcining of the precursors. In this effort, several different calcine temperatures were investigated to evaluate the effect on initial phase formation (in the calcined precursors), thermal expansion of the pressed pellets during heating, and mineralogy and porosity of the final product.

  20. Gamma-Ray Burst Precursor Activity as Observed with BATSE

    NASA Technical Reports Server (NTRS)

    Koshut, Thomas M.; Kouveliotou, Chryssa; Paciesas, William S.; vanParadijs, Jan; Pendleton, Geoffrey N.; Briggs, Michael S.; Fishman, Gerald J.; Meegan, Charles A.

    1995-01-01

    Gamma-ray burst time histories often consist of multiple episodes of emission with the count rate dropping to the background level between adjacent episodes. We define precursor activity as any case in which the first episode (referred to as the precursor episode) has a lower peak intensity than that of the remaining emission (referred to as the main episode) and is separated from the remaining burst emission by a background interval that is at least as long as the remaining emission. We find that approx. 3% of the bursts observed with the Burst and Transient Source Experiment (BATSE) on Compton Gamma Ray Observatory (CGRO) satisfy this definition. We present the results of a study of the properties of these events. The spatial distribution of these sources is consistent with that of the larger set of all BATSE gamma-ray bursts: inhomogeneous and isotropic. A correlation between the duration of the precursor emission and the duration of the main episode emission is observed at about the 3 sigma confidence level. We find no meaningful significant correlations between or among any of the other characteristics of the precursor or main episode emission. It appears that the characteristics of the main episode emission are independent of the existence of the precursor emission.

  1. Subcellular Distribution of Glutathione Precursors in Arabidopsis thaliana

    PubMed Central

    Koffler, Barbara Eva; Maier, Romana; Zechmann, Bernd

    2011-01-01

    Abstract Glutathione is an important antioxidant and has many important functions in plant development, growth and defense. Glutathione synthesis and degradation is highly compartment-specific and relies on the subcellular availability of its precursors, cysteine, glutamate, glycine and γ-glutamylcysteine especially in plastids and the cytosol which are considered as the main centers for glutathione synthesis. The availability of glutathione precursors within these cell compartments is therefore of great importance for successful plant development and defense. The aim of this study was to investigate the compartment-specific importance of glutathione precursors in Arabidopsis thaliana. The subcellular distribution was compared between wild type plants (Col-0), plants with impaired glutathione synthesis (glutathione deficient pad2-1 mutant, wild type plants treated with buthionine sulfoximine), and one complemented line (OE3) with restored glutathione synthesis. Immunocytohistochemistry revealed that the inhibition of glutathione synthesis induced the accumulation of the glutathione precursors cysteine, glutamate and glycine in most cell compartments including plastids and the cytosol. A strong decrease could be observed in γ-glutamylcysteine (γ-EC) contents in these cell compartments. These experiments demonstrated that the inhibition of γ-glutamylcysteine synthetase (GSH1) – the first enzyme of glutathione synthesis – causes a reduction of γ-EC levels and an accumulation of all other glutathione precursors within the cells. PMID:22050910

  2. A novel class of peptide pheromone precursors in ascomycetous fungi

    PubMed Central

    Schmoll, Monika; Seibel, Christian; Tisch, Doris; Dorrer, Marcel; Kubicek, Christian P

    2010-01-01

    Recently, sexual development in the heterothallic ascomycete Trichoderma reesei (anamorph of Hypocrea jecorina) has been achieved and thus initiated attempts to elucidate regulation and determinants of this process. While the α-type pheromone of this fungus fits the consensus known from other fungi, the assumed a-type peptide pheromone precursor shows remarkably unusual characteristics: it comprises three copies of the motif (LI)GC(TS)VM thus constituting a CAAX domain at the C-terminus and two Kex2-protease sites. This structure shares characteristics of both a- and α-type peptide pheromone precursors. Presence of hybrid-type peptide pheromone precursor 1 (hpp1) is essential for male fertility, thus indicating its functionality as a peptide pheromone precursor, while its phosphorylation site is not relevant for this process. However, sexual development in a female fertile background is not perturbed in the absence of hpp1, which rules out a higher order function in this process. Open reading frames encoding proteins with similar characteristics to HPP1 were also found in Fusarium spp., of which Fusarium solani still retains a putative a-factor-like protein, but so far in no other fungal genome available. We therefore propose the novel class of h-type (hybrid) peptide pheromone precursors with H. jecorina HPP1 as the first member of this class. PMID:20735770

  3. Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy

    PubMed Central

    2017-01-01

    Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE), a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80%) and yield (>70%). Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies. PMID:28122047

  4. Precursor conversion kinetics and the nucleation of cadmium selenide nanocrystals.

    PubMed

    Owen, Jonathan S; Chan, Emory M; Liu, Haitao; Alivisatos, A Paul

    2010-12-29

    The kinetics of cadmium selenide (CdSe) nanocrystal formation was studied using UV-visible absorption spectroscopy integrated with an automated, high-throughput synthesis platform. Reaction of anhydrous cadmium octadecylphosphonate (Cd-ODPA) with alkylphosphine selenides (1, tri-n-octylphosphine selenide; 2, di-n-butylphenylphosphine selenide; 3, n-butyldiphenylphosphine selenide) in recrystallized tri-n-octylphosphine oxide was monitored by following the absorbance of CdSe at λ = 350 nm, where the extinction coefficient is independent of size, and the disappearance of the selenium precursor using {(1)H}(31)P NMR spectroscopy. Our results indicate that precursor conversion limits the rate of nanocrystal nucleation and growth. The initial precursor conversion rate (Q(o)) depends linearly on [1] (Q(o)(1) = 3.0-36 μM/s) and decreases as the number of aryl groups bound to phosphorus increases (1 > 2 > 3). Changes to Q(o) influence the final number of nanocrystals and thus control particle size. Using similar methods, we show that changing [ODPA] has a negligible influence on precursor reactivity while increasing the growth rate of nuclei, thereby decreasing the final number of nanocrystals. These results are interpreted in light of a mechanism where the precursors react in an irreversible step that supplies the reaction medium with a solute form of the semiconductor.

  5. Partitioning Tungsten between Matrix Precursors and Chondrule Precursors through Relative Settling

    NASA Astrophysics Data System (ADS)

    Hubbard, Alexander

    2016-08-01

    Recent studies of chondrites have found a tungsten isotopic anomaly between chondrules and matrix. Given the refractory nature of tungsten, this implies that W was carried into the solar nebula by at least two distinct families of pre-solar grains. The observed chondrule/matrix split requires that the distinct families were kept separate during the dust coagulation process, and that the two families of grain interacted with the chondrule formation mechanism differently. We take the co-existence of different families of solids in the same general orbital region at the chondrule-precursor size as given, and explore the requirements for them to have interacted with the chondrule formation process at significantly different rates. We show that this sorting of families of solids into chondrule- and matrix-destined dust had to have been at least as powerful a sorting mechanism as the relative settling of aerodynamically distinct grains at least two scale heights above the midplane. The requirement that the chondrule formation mechanism was correlated in some fashion with a dust-grain sorting mechanism argues strongly for spatially localized chondrule formation mechanisms such as turbulent dissipation in non-thermally ionized disk surface layers, and argues against volume-filling mechanisms such as planetesimal bow shocks.

  6. Solvothermal Molecular Precursor Routes to Semiconductor Film and Crystal Growth

    NASA Astrophysics Data System (ADS)

    Gillan, Edward G.

    2002-08-01

    This research project explored the utility of molecular precursor decomposition in superheated non-aqueous solvents directed towards semiconductor crystal growth. Reactions were run in toluene, THF, and under solvent free conditions. An in situ precursor synthesis and decomposition resulted in GaN nanoparticles from simple starting materials (GaCl(3) and NaN(3)). Particle sizes range from about 10 to hundreds of nanometers. Upon annealing to 1000 degrees C, the poorly crystalline products ordered into crystalline hexagonal GaN and luminescence. The conversion of synthesized organometallic dimeric gallium amino precursors to GaN was less successful; however they showed some utility in vapor phase film growth. Silver and silver sulfide nanoparticles were also produced in a solvothermal system via silver azide decomposition producing particles in the 100 mn to micron size regime.

  7. Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply

    PubMed Central

    O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

    2014-01-01

    Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components. PMID:25487822

  8. Thin film solar cells by selenization sulfurization using diethyl selenium as a selenium precursor

    SciTech Connect

    Dhere, Neelkanth G.; Kadam, Ankur A.

    2009-12-15

    A method of forming a CIGSS absorber layer includes the steps of providing a metal precursor, and selenizing the metal precursor using diethyl selenium to form a selenized metal precursor layer (CIGSS absorber layer). A high efficiency solar cell includes a CIGSS absorber layer formed by a process including selenizing a metal precursor using diethyl selenium to form the CIGSS absorber layer.

  9. Research of Hydro-Geological Precursors of Earthquakes in Armenia

    NASA Astrophysics Data System (ADS)

    Pashayan, R.

    2007-12-01

    The observations of hydro-geological regime of underground waters in observed boreholes began in Armenia in 1986. Now these work is concentrated in National Seismic Service. For a long time observations are carried out studying several parameters (debit, temperature, chemical and gas composition) in several deposits of carbon mineral waters of Armenia. The interpretation of materials shows that that a number of strong and medium-strength earthquakes are accompanied by anomal changes in the level of underground waters. Regarding mineral waters, in connection with earthquakes some parameters are immediately changed: debit, temperature, chemical and gas composition. The study of hydrogeodynamic characteristics of precursors specify that the quantity of registered hydrogeodynamic precursors decreases with the increase of epicentrical distance. The majority of precursors is registered at the distance of 200 km from epicenter. There is a tendency of gradual increase of time and amplitude of a precursor of an earthquake depending on the rise of magnitude and epicentral distance. The behaviour of hydrogeodynamic precursors depends on the angle between the faults, to which this or that borehole reaches; with increase of this angle the deformation in the zone of the fault during the preparation of earthquakes is stronger, than in terms of small angles. 1. S1 2. Earthquake processes, Precursors and Forecasts 3. Garni Geophysical Observatory of the National Academy of Sciences of Armenia, 375019, Yerevan, Republic of Armenia, email: hakhleon@sci.am 4. O 5. 10808801 6. Artavazd Payment Type: select 'Purchase Order' PO Number: AGU WAIVER Billing Address: Enter Your Institution City: Enter Your City Country Code: Enter Your Country Name: Enter Your Name Phone: Enter Your Telephone Number

  10. Generation of Vibrationally Excited HCP from a Stable Synthetic Precursor

    NASA Astrophysics Data System (ADS)

    Hull, Alexander W.; Jiang, Jun; Erickson, Trevor J.; Womack, Carrie; Nava, Matthew; Cummins, Christopher; Field, Robert W.

    2015-06-01

    HCP belongs to a class of reactive small molecules with much interest to spectroscopists. It bears certain similarities to HCN, including a strong {A}(bent) - {X}(linear) ultraviolet transition, associated with the HCP-HPC isomerization pathway. HCP has traditionally been generated by the in situ reaction of PH_3 and acetylene. In this talk, we will discuss a recently developed synthetic precursor molecule, 1,1-((triphenylphosphoranylidene)methyl)-9,10-phosphanoanthracene. At temperatures above 200 degrees Celsius, this precursor is thought to release HCP in a vibrationally excited state. We will present preliminary spectra on this system obtained by LIF and chirped pulse millimeter wave spectroscopy.

  11. High Temperature Stability of Binary Microstructures Derived from Liquid Precursors

    DTIC Science & Technology

    1994-06-30

    substrates have bee.t used to produce single crystal ferroelectric films. Sapphire substrates were used for Nb - doped PZT thin films.25 The growth of...Epitaxial Growth of PbTiO3 Thin Films on (100) SrTiO3 from Solution Precursors Andreas Seifert, Fred F. Lange and James S. Speck Technical Report No...12 Abstract: A mixed alkoxide liquid precursor was used to form epitaxial PbTiO3 thin films by spin-coating on cubic (001) SrTiO3 substrates. The films

  12. Glutamine: Precursor or nitrogen donor for citrulline synthesis?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton, versus nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutami...

  13. Precursors for ornithine and citrulline synthesis in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrulline (CIT) is an amino acid synthesized by gut and utilized for the synthesis of the conditionally essential amino acid arginine (ARG). In turn, the immediate precursor for CIT synthesis, ornithine (ORN), can originate from proline (PRO) and glutamine (GLN) via ornithine aminotransferase (OAT,...

  14. Glutamine: precursor or nitrogen donor for citrulline synthesis?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glutamine (Gln) is considered the main precursor for citrulline (Cit) synthesis, but no attempts have been made to differentiate the contribution of Gln carbon (Gln-C) skeleton vs. the nonspecific contribution through NH3 and CO2. To study the contribution of dietary Gln-N to the synthesis of Cit, t...

  15. Tachykinin-related peptide precursors in two cockroach species.

    PubMed

    Predel, Reinhard; Neupert, Susanne; Roth, Steffen; Derst, Christian; Nässel, Dick R

    2005-07-01

    Tachykinins and tachykinin-related peptides (TKRPs) play major roles in signaling in the nervous system and intestine of both invertebrates and vertebrates. Here we have identified cDNAs encoding precursors of multiple TKRPs from the cockroaches Leucophaea maderae and Periplaneta americana. All nine LemTKRPs that had been chemically isolated in earlier experiments could be identified on the precursor of L. maderae. Four previously unidentified LemTKRPs were found in addition on the precursor. The P. americana cDNA displayed an open reading frame very similar to that of L. maderae with 13 different TKRPs. MALDI-TOF mass spectra from tissues of both species confirms the presence of all the TKRPs encoded on the precursor plus two additional peptides that are cleavage products of the N-terminally extended TKRPs. A tissue-specific distribution of TKRPs was observed in earlier experiments at isolation from brain and midgut of L. maderae. Our data do not suggest a differential gene expression but a different efficacy in processing of LemTKRP-2 and Lem/PeaTKRP-3 in the brain and intestine, respectively. This results in a gut-specific accumulation of these extended peptides, whereas in the brain their cleavage products, LemTKRP-1 and LemTKRP-3(11-19), are most abundant. Mass spectrometric analysis demonstrated the occurrence of the different TKRPs in single glomeruli of the tritocerebrum and in cells of the optical lobe.

  16. Methionine as a Precursor of Ethylene—Commentary

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lieberman et al. showed in a 1966 publication of Plant Physiology that methionine is a precursor of ethylene. It was the first paper that showed ethylene carbons are derived from carbons 3 and 4 of methionine. This paper catalyzed remarkable interest among plant biologists to elucidate the biosynth...

  17. Organosilane Polymers. IV. Polycarbosilane Precursors for Silicon Carbide.

    DTIC Science & Technology

    1981-01-01

    The current objectives of this project are: (1) optimized preparations of tractable polycarbosilane precursors for silicon carbide ; (2) conversion of...such polycarbosilanes to silicon carbide including shaped articles thereof, such as fibers; and (3) development of fundamental understanding of the...vinylic or chloromethyl (ClCH2-) silanes. These polymers are directly convertible to silicon carbide compositions by atmospheric pressure pyrolysis

  18. RIVERBANK FILTRATION: FATE OF DBP PRECURSORS AND SELECTED MICROORGANISMS

    EPA Science Inventory

    The fate of disinfection by-product (DBP) precursors and selected microorganisms during riverbank filtration (RBF) was monitored at three different mid-Western drinking water utilities. At all three sites, filtration (RBF) was monitored at three different mid-Western drinking wa...

  19. Terrorist Precursor Crimes: Issues and Options for Congress

    DTIC Science & Technology

    2007-05-24

    activity, especially with regard to crimes conducted for the purpose of fundraising , takes place in wealthy Western countries, including the United...Crimes for Fundraising and Longevity of Terror Campaigns . . . 21 Precursor Crimes’ Effect on Threat Environment...for the purpose of fundraising , is thought to take place in wealthy Western countries, including the United States. This report provides an overview

  20. NASA's Accident Precursor Analysis Process and the International Space Station

    NASA Technical Reports Server (NTRS)

    Groen, Frank; Lutomski, Michael

    2010-01-01

    This viewgraph presentation reviews the implementation of Accident Precursor Analysis (APA), as well as the evaluation of In-Flight Investigations (IFI) and Problem Reporting and Corrective Action (PRACA) data for the identification of unrecognized accident potentials on the International Space Station.

  1. Process for producing ceramic nitrides anc carbonitrides and their precursors

    DOEpatents

    Brown, G.M.; Maya, L.

    1987-02-25

    A process for preparing ceramic nitrides and carbon nitrides in the form of very pure, fine particulate powder. Appropriate precursors is prepared by reaching a transition metal alkylamide with ammonia to produce a mixture of metal amide and metal imide in the form of an easily pyrolyzable precipitate.

  2. Precursors to Numeracy in Kindergartners with Specific Language Impairment

    ERIC Educational Resources Information Center

    Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

    2011-01-01

    The present study investigated to what extent children with specific language impairment (SLI) differ in their early numeracy skills, when compared to normal language achieving (NLA) children. It was also explored which precursors were related to the early numeracy skills in both groups. Sixty-one children with SLI (6; 1 years) and 111 NLA…

  3. Manganite perovskite ceramics, their precursors and methods for forming

    DOEpatents

    Payne, David Alan; Clothier, Brent Allen

    2015-03-10

    Disclosed are a variety of ceramics having the formula Ln.sub.1-xM.sub.xMnO.sub.3, where 0.Itoreq.x.Itoreq.1 and where Ln is La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu or Y; M is Ca, Sr, Ba, Cd, or Pb; manganite precursors for preparing the ceramics; a method for preparing the precursors; and a method for transforming the precursors into uniform, defect-free ceramics having magnetoresistance properties. The manganite precursors contain a sol and are derived from the metal alkoxides: Ln(OR).sub.3, M(OR).sub.2 and Mn(OR).sub.2, where R is C.sub.2 to C.sub.6 alkyl or C.sub.3 to C.sub.9 alkoxyalkyl, or C.sub.6 to C.sub.9 aryl. The preferred ceramics are films prepared by a spin coating method and are particularly suited for incorporation into a device such as an integrated circuit device.

  4. The molecular evolution of the allatostatin precursor in cockroaches.

    PubMed

    Bellés, X; Graham, L A; Bendena, W G; Ding, Q I; Edwards, J P; Weaver, R J; Tobe, S S

    1999-01-01

    Allatostatins (ASTs) of the Tyr/Phe-Xaa-Phe-Gly Leu/Ile-NH2 family are a group of insect neuropeptides that inhibit juvenile hormone biosynthesis by the corpora allata. We have obtained genomic DNA sequences that specify the preproallatostatin precursor for the cockroaches, Blatta orientalis, Blattella germanica, Blaberus (cranufer and Supella longipalpa. The sequences obtained are similar to those of Diploptera punctata and Periplaneta americana reported previously. The precursors of all these cockroach species are similar in size, and the organization of the ASTs that they contain (there are 13 or 14, depending on the species) have been conserved. With the sequences of these precursors, and using the homologous sequence in the orthopteran Schistocera gregari as an outgroup, a phylogenetic analysis using parsimony was carried out. The dendrograms obtained from these analyses. using the amino acid as well as the nucleotide sequences, are comparable with current models for cockroach phylogeny. Parsimony analysis was also used to study the genealogy of the different ASTs within the same precursor. Results suggest that the AST sequences were generated through a process of internal gene duplication which occurred before these species diverged from each other in evolutionary time.

  5. Process for producing ceramic nitrides and carbonitrides and their precursors

    DOEpatents

    Brown, Gilbert M.; Maya, Leon

    1988-01-01

    A process for preparing ceramic nitrides and carbonitrides in the form of very pure, fine particulate powder. Appropriate precursor is prepared by reacting a transition metal alkylamide with ammonia to produce a mixture of metal amide and metal imide in the form of an easily pyrolyzable precipitate.

  6. Technical note: Methionine, a precursor of methane in living plants

    NASA Astrophysics Data System (ADS)

    Lenhart, K.; Althoff, F.; Greule, M.; Keppler, F.

    2014-11-01

    When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued, not only about their contribution to the global methane budget, but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds identified. We made use of stable isotope techniques to verify in vivo formation of methane and, in order to identify the carbon precursor, 13C-positionally labelled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labelled methionine clearly identified the sulphur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia). Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

  7. Technical Note: Methionine, a precursor of methane in living plants

    NASA Astrophysics Data System (ADS)

    Lenhart, K.; Althoff, F.; Greule, M.; Keppler, F.

    2015-03-01

    When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued not only about their contribution to the global methane budget but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds to be identified. We made use of stable isotope techniques to verify the in vivo formation of methane, and, in order to identify the carbon precursor, 13C positionally labeled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labeled methionine clearly identified the sulfur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia). Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

  8. College Student Stress: A Predictor of Eating Disorder Precursor Behaviors

    ERIC Educational Resources Information Center

    Shelton, Virginia L.; Valkyrie, Karena T.

    2010-01-01

    Eating disorders are compulsive behaviors that can consume a person's life to the point of becoming life threatening. Previous research found stress associated with eating disorders. College can be a stressful time. If stress predicted precursor behaviors to eating disorders, then counselors would have a better chance to help students sooner. This…

  9. Developmental Dyslexia: Early Precursors, Neurobehavioral Markers, and Biological Substrates

    ERIC Educational Resources Information Center

    Benasich, April A., Ed.; Fitch, R. Holly, Ed.

    2012-01-01

    Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…

  10. Quaternary amines as nitrosamine precursors: a role for consumer products?

    PubMed

    Kemper, Jerome M; Walse, Spencer S; Mitch, William A

    2010-02-15

    Nitrosamine formation has been associated with wastewater-impacted waters, but specific precursors within wastewater effluents have not been identified. Experiments indicated that nitrosamines form in low yields from quaternary amines, and that the nitrosamines form from the quaternary amines themselves, not just lower order amine impurities. Polymeric and benzylated quaternary amines were more potent precursors than monomeric quaternary alkylamines. Pretreatment of quaternary amines with ozone or free chlorine, which deactivate lower order amine impurities, did not significantly reduce nitrosamine formation. The nitrosamine formation pathway is unclear but experiments indicated that transformation of quaternary amines to lower order amine precursors via Hofmann elimination was not involved. Experiments suggest that the pathway may involve quaternary amine degradation by amidogen or chloramino radicals formed from chloramines. Quaternary amines are significant constituents of consumer products, including shampoos, detergents, and fabric softeners. Although quaternary amines may be removed by sedimentation during wastewater treatment, their importance should be evaluated on a case-by-case basis. The high loadings from consumer products may enable the portion not removed to serve as precursors.

  11. Urinary excretion of morphine and biosynthetic precursors in mice

    PubMed Central

    Grobe, Nadja; Lamshöft, Marc; Orth, Robert G.; Dräger, Birgit; Kutchan, Toni M.; Zenk, Meinhart H.; Spiteller, Michael

    2010-01-01

    It has been firmly established that humans excrete a small but steady amount of the isoquinoline alkaloid morphine in their urine. It is unclear whether it is of dietary or endogenous origin. There is no doubt that a simple isoquinoline alkaloid, tetrahydropapaveroline (THP), is found in human and rodent brain as well as in human urine. This suggests a potential biogenetic relationship between both alkaloids. Unlabeled THP or [1,3,4-D3]-THP was injected intraperitoneally into mice and the urine was analyzed. This potential precursor was extensively metabolized (96%). Among the metabolites found was the phenol-coupled product salutaridine, the known morphine precursor in the opium poppy plant. Synthetic [7D]-salutaridinol, the biosynthetic reduction product of salutaridine, injected intraperitoneally into live animals led to the formation of [7D]-thebaine, which was excreted in urine. [N-CD3]-thebaine was also administered and yielded [N-CD3]-morphine and the congeners [N-CD3]-codeine and [N-CD3]-oripavine in urine. These results show for the first time that live animals have the biosynthetic capability to convert a normal constituent of rodents, THP, to morphine. Morphine and its precursors are normally not found in tissues or organs, presumably due to metabolic breakdown. Hence, only that portion of the isoquinoline alkaloids excreted in urine unmetabolized can be detected. Analysis of urine by high resolution-mass spectrometry proved to be a powerful method for tracking endogenous morphine and its biosynthetic precursors. PMID:20421505

  12. The telescience experiment progamme TELEX for the Columbus Precursor Flights

    NASA Astrophysics Data System (ADS)

    Jungius, C. B.; Limbourg, M. C.; Wittmann, K.; Bennett, E.

    1992-08-01

    The paper overviews the telescience experiment program TELEX developed by the Microgravity User Support Centre (MUSC) and the Belgium User Support and Operation Centre for missions such as Columbus Precursor Flights. TELEX will be used to develop, test, and demonstrate in a stepwise manner the Columbus laboratory operations concept. Special attention is given to the TELEX operations and implementation.

  13. Environment Conscious, Biomorphic Ceramics from Pine and Jelutong Wood Precursors

    NASA Technical Reports Server (NTRS)

    Singh, Mrityunjay; Yee, Bo-Moon; Gray, Hugh R. (Technical Monitor)

    2002-01-01

    Environment conscious, biomorphic ceramics have been fabricated from pine and jelutong wood precursors. A carbonaceous preform is produced through wood pyrolysis and subsequent infiltration with oxides (ZrO2 sols) and liquid silicon to form ceramics. These biomorphic ceramics show a wide variety of microstructures, densities, and hardness behavior that are determined by the type of wood and infiltrants selected.

  14. CARBONACEOUS MATTER PRECURSORS AND METAMORPHIC CONDITIONS IN THERMALLY PROCESSED CHONDRITES

    NASA Astrophysics Data System (ADS)

    Quirico, E.; Montagnac, G.; Rouzaud, J.; Bonal, L.; Bourot-Denise, M.; Duber, S.; Reynard, B.

    2009-12-01

    Unravelling the origin of carbonaceous matter in pristine chondrites requires the understanding of the effect of post-accretion processes. In chondrites of petrologic type 3, thermal metamorphism modified to various extents the composition and structure of carbonaceous matter. Interestingly, this process controls the degree of structural order of carbonaceous matter, and clues on the thermal history of the parent body may be recovered from the physico-chemical study of carbonaceous matter. Following this framework, geothermometers based on Raman spectrometry of carbonaceous matter and covering a wide range of temperatures (100-650 °C) have been developed over recent years, both on terrestrial rocks and chondrites. While Raman data have been largely interpreted in terms of temperature, they are also the fingerprint of certain metamorphic conditions, especially in the low temperature range relevant to poorly ordered carbonaceous matter. This study investigates the Raman spectra of two series of chondritic carbonaceous matter and coal samples formed from different precursors and under different metamorphic conditions. The Raman spectra of Polyaromatic Carbonaceous Matter (PCM) from 42 chondrites and 27 coal samples, measured with visible (514 nm) and ultra-violet (244 nm) excitation wavelengths, are analyzed. The Raman spectra of low rank coals and chondrites of petrologic types 1 and 2, which contain the more disordered PCM, reflect the distinct carbon structures of their precursors. The 514 nm Raman spectra of high rank coals and chondrites of petrologic type 3 exhibit continuous and systematic spectral differences reflecting different carbon structures present during the metamorphism event. They result from differences in the chemical structures of the precursors concerning for instance the reticulation of polyaromatic units or an abundance of ether functional groups, or possibly from a lack of carbonization processes to efficiently expel oxygen heteroatoms, due

  15. Making Single-Source Precursors of Ternary Semiconductors

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius; Banger, Kulbindre K.

    2007-01-01

    A synthesis route has been developed for the commercial manufacture of single- source precursors of chalcopyrite semiconductor absorber layers of thin-film solar photovoltaic cells. A closely related class of single-source precursors of these semiconductors, and their synthesis routes, were reported in "Improved Single-Source Precursors for Solar-Cell Absorbers" (LEW-17445-1), NASA Tech Briefs, Vol. 31, No. 6 (June 2007), page 56. The present synthesis route is better suited to commercialization because it is simpler and involves the use of commercially available agents, yet offers the flexibility needed for synthesis of a variety of precursors. A single-source precursor of the type of interest here is denoted by the general formula L2M'(mu-ER)2M(ER)2, where L signifies a Lewis base; M signifies Al, In, or Ga; M' signifies Ag or Cu; R signifies an alkyl, aryl, silyl, or perfluorocarbon group; E signifies O, S, Se, or Te; and mu signifies a bridging ligand. This compound can be synthesized in a "one-pot" procedure from ingredients that are readily available from almost any chemical supplier. In a demonstration, the following synthesis was performed: Under anaerobic conditions, InCl3 was reacted with sodium ethanethiolate in methanol in a 1:4 molar ratio to afford the ionic stable intermediate compound Na+[In(SEt)4]- (where Et signifies ethyl group). After approximately 15 minutes, a heterogeneous solution of CuCl and the Lewis base PPh3 (where Ph signifies phenyl) in a 1:2 ratio in a mixture of CH3CN and CH2Cl2 was added directly to the freshly prepared Na+[In(SEt)4]-. After 24 hours, the reaction was essentially complete. The methanolic solution was concentrated, then the product was extracted with CH2Cl2, then the product was washed with dry ether and pentane. The product in its final form was a creamy white solid. Spectroscopic and elemental analysis confirmed that the product was (PPh3)2Cu(mu-SEt)2In(mu-SEt)2, which is known to be a precursor of the ternary

  16. Antimicrobial peptide precursor structures suggest effective production strategies.

    PubMed

    Vassilevski, Alexander A; Kozlov, Sergey A; Grishin, Eugene V

    2008-01-01

    Antimicrobial peptides (AMPs) constitute a diverse group of compounds that serve a common goal that is host organism defense from infection. Due to their antimicrobial properties, these molecules attract practical interest as potential antibiotics for medical and veterinary use as well as enhancers of plant disease resistance for agriculture. Broad AMP utilization is restricted by the expensiveness of their production using conventional chemical synthesis. For this reason, a number of chimeric genes have been developed for recombinant AMP production in prokaryotes. However, recombinant peptide instability and/or high toxicity to host cells dramatically reduce the yields. In this paper, we review patented strategies of fusion protein design for AMP production. In several cases, the proposed strategies clearly mimic the organization of natural AMP precursor proteins. We describe the main principals of natural AMP precursor organization and fusion constructs adopted and/or artificially designed by man.

  17. Fission-Based Electric Propulsion for Interstellar Precursor Missions

    SciTech Connect

    HOUTS,MICHAEL G.; LENARD,ROGER X.; LIPINSKI,RONALD J.; PATTON,BRUCE; POSTON,DAVID; WRIGHT,STEVEN A.

    1999-11-03

    This paper reviews the technology options for a fission-based electric propulsion system for interstellar precursor missions. To achieve a total {Delta}V of more than 100 km/s in less than a decade of thrusting with an electric propulsion system of 10,000s Isp requires a specific mass for the power system of less than 35 kg/kWe. Three possible configurations are described: (1) a UZrH-fueled,NaK-cooled reactor with a steam Rankine conversion system,(2) a UN-fueled gas-cooled reactor with a recuperated Brayton conversion system, and (3) a UN-fueled heat pipe-cooled reactor with a recuperated Brayton conversion system. All three of these systems have the potential to meet the specific mass requirements for interstellar precursor missions in the near term. Advanced versions of a fission-based electric propulsion system might travel as much as several light years in 200 years.

  18. Low-temperature precursors for ceramic oxide catalysts

    SciTech Connect

    Apblett, A.W.; Georgieva, G.D.; Mague, J.T.; Matta, E.J.; Reinhardt, L.E.

    1997-12-31

    Metal complexes of 2-oximinopropionates (M=Ce{sup 3+}, Sm{sup 3+}, Ni{sup 2+}, Fe{sup 2+}) are readily prepared by precipitation reactions of aqueous solutions of the metal salts with sodium 2-oximinopropionate. These complexes decompose at relatively low temperatures (110-164{degrees}C) to afford either carbonates (M=Ni, Sm) or oxides (M=Ce, Fe) as high surface area materials. The cerium and samarium complexes are isostructural and it is therefore possible to prepare a solid solution containing the two lanthanide metals which serves as a precursor for the oxide ion-conductor, Ce{sub 0.80}Sm{sub 0.20}O{sub 1.9}. Similarly, solid solutions of nickel and iron 2-oximinopropionates serves as precursors for nickel ferrite, NiFe{sub 2}O{sub 4}, in an unusual fibrous morphology which may be suitable as a high surface area catalytic support.

  19. The role of catalyst precursor anions in coal gasification

    SciTech Connect

    Abotsi, G.M.K.

    1992-01-01

    The aims of the proposed project are to enrich our understanding of the roles of various aqueous soluble catalyst precursor anions on the surface electrical properties of coal and to ascertain the influence of the surface charge on the adsorption, dispersion, and activities of calcium and potassium. These goals will be achieved by impregnating a lignite and its demineralized derivative with calcium or potassium catalyst precursors containing acetate (CH{sub 3}COO{minus}), chloride (Cl{minus}), nitrate (NO{sub 3}{minus}), sulfate (SO{sub 4}{sup 2{minus}}), and carbonate (CO{sub 3}{sup 2{minus}}) anions. Catalyst loading will be conducted under well-controlled conditions of solution pH and ionic strength.

  20. Structural basis for precursor protein-directed ribosomal peptide macrocyclization

    PubMed Central

    Li, Kunhua; Condurso, Heather L.; Li, Gengnan; Ding, Yousong; Bruner, Steven D.

    2016-01-01

    Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides whose members target proteases with potent reversible inhibition. The product structure is constructed by three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here, we describe the detailed structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases, MdnC and MdnB, interact with a conserved α-helix of the precursor peptide using a novel precursor peptide recognition mechanism. The results provide insight into the unique protein/protein interactions key to the chemistry, suggest an origin of the natural combinatorial synthesis of microviridin peptides and provide a framework for future engineering efforts to generate designed compounds. PMID:27669417

  1. Structural basis for precursor protein-directed ribosomal peptide macrocyclization

    SciTech Connect

    Li, Kunhua; Condurso, Heather L.; Li, Gengnan; Ding, Yousong; Bruner, Steven D.

    2016-11-11

    Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein–protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.

  2. Atomic scale simulation of carbon nanotube nucleation from hydrocarbon precursors

    PubMed Central

    Khalilov, Umedjon; Bogaerts, Annemie; Neyts, Erik C.

    2015-01-01

    Atomic scale simulations of the nucleation and growth of carbon nanotubes is essential for understanding their growth mechanism. In spite of over twenty years of simulation efforts in this area, limited progress has so far been made on addressing the role of the hydrocarbon growth precursor. Here we report on atomic scale simulations of cap nucleation of single-walled carbon nanotubes from hydrocarbon precursors. The presented mechanism emphasizes the important role of hydrogen in the nucleation process, and is discussed in relation to previously presented mechanisms. In particular, the role of hydrogen in the appearance of unstable carbon structures during in situ experimental observations as well as the initial stage of multi-walled carbon nanotube growth is discussed. The results are in good agreement with available experimental and quantum-mechanical results, and provide a basic understanding of the incubation and nucleation stages of hydrocarbon-based CNT growth at the atomic level. PMID:26691537

  3. Structural basis for precursor protein-directed ribosomal peptide macrocyclization.

    PubMed

    Li, Kunhua; Condurso, Heather L; Li, Gengnan; Ding, Yousong; Bruner, Steven D

    2016-11-01

    Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein-protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.

  4. Detection of hydrothermal precursors to large northern california earthquakes.

    PubMed

    Silver, P G; Valette-Silver, N J

    1992-09-04

    During the period 1973 to 1991 the interval between eruptions from a periodic geyser in Northern California exhibited precursory variations 1 to 3 days before the three largest earthquakes within a 250-kilometer radius of the geyser. These include the magnitude 7.1 Loma Prieta earthquake of 18 October 1989 for which a similar preseismic signal was recorded by a strainmeter located halfway between the geyser and the earthquake. These data show that at least some earthquakes possess observable precursors, one of the prerequisites for successful earthquake prediction. All three earthquakes were further than 130 kilometers from the geyser, suggesting that precursors might be more easily found around rather than within the ultimate rupture zone of large California earthquakes.

  5. Glycerol, an underestimated flavor precursor in the Maillard reaction.

    PubMed

    Smarrito-Menozzi, Candice; Matthey-Doret, Walter; Devaud-Goumoens, Stéphanie; Viton, Florian

    2013-10-30

    The objective of the present work was to investigate in depth the role of glycerol in Maillard reactions and its potential to act as an active flavor precursor. Reactions using isotopically labeled compounds (various reducing sugars, proline, and glycerol) unambiguously demonstrated that, in addition to its role of solvent, glycerol actively contributes to the formation of proline-specific compounds in Maillard model systems. Additionally, rhamnose and fucose/proline/glycerol systems generated the 2-propionyl-1(3),4,5,6-tetrahydropyridines, known for their roasty, popcorn aroma. Their formation from such systems is unprecedented. The results presented here have direct implications for flavor generation during thermal processing of foods containing glycerol, which is a ubiquitous food ingredient and an underestimated flavor precursor.

  6. Percolation-based precursors of transitions in extended systems

    PubMed Central

    Rodríguez-Méndez, Víctor; Eguíluz M, Víctor M.; Hernández-García, Emilio; Ramasco, José J.

    2016-01-01

    Abrupt transitions are ubiquitous in the dynamics of complex systems. Finding precursors, i.e. early indicators of their arrival, is fundamental in many areas of science ranging from electrical engineering to climate. However, obtaining warnings of an approaching transition well in advance remains an elusive task. Here we show that a functional network, constructed from spatial correlations of the system’s time series, experiences a percolation transition way before the actual system reaches a bifurcation point due to the collective phenomena leading to the global change. Concepts from percolation theory are then used to introduce early warning precursors that anticipate the system’s tipping point. We illustrate the generality and versatility of our percolation-based framework with model systems experiencing different types of bifurcations and with Sea Surface Temperature time series associated to El Niño phenomenon. PMID:27412567

  7. Percolation-based precursors of transitions in extended systems

    NASA Astrophysics Data System (ADS)

    Rodríguez-Méndez, Víctor; Eguíluz M, Víctor M.; Hernández-García, Emilio; Ramasco, José J.

    2016-07-01

    Abrupt transitions are ubiquitous in the dynamics of complex systems. Finding precursors, i.e. early indicators of their arrival, is fundamental in many areas of science ranging from electrical engineering to climate. However, obtaining warnings of an approaching transition well in advance remains an elusive task. Here we show that a functional network, constructed from spatial correlations of the system’s time series, experiences a percolation transition way before the actual system reaches a bifurcation point due to the collective phenomena leading to the global change. Concepts from percolation theory are then used to introduce early warning precursors that anticipate the system’s tipping point. We illustrate the generality and versatility of our percolation-based framework with model systems experiencing different types of bifurcations and with Sea Surface Temperature time series associated to El Niño phenomenon.

  8. The absorption spectra of carbonates and their precursors.

    NASA Astrophysics Data System (ADS)

    Koike, C.; Chihara, H.; Suto, H.

    The carbonates calcite and dolomite have been discovered in the dust shells of evolved stars (Kemper et al. 2002) and young proto stars (Ceccarelli et al. 2002). The mechanism for carbonate formation with a aqueous or non-aqueous process were discussed in their papers. These processes have not yet been reproduced in a laboratory experiment. First of all, we measured the mass absorption spectra of varous carbonates were measured in the mid- and far-infrared region. These spectra show very strong and broad peaks in the far-infrared region. The calcite and dolomite have peaks at about 92 microns and 63 microns, respectively. The alternative process of carbonates has not yet been clear. We investigate the alternative process measuring the spectra of the precursors of carbonates. We will report the preliminary results and discuss about the alternative process comparing the measured spectra of the precursors with the observation.

  9. Microwave-assisted on-spot derivatization for gas chromatography-mass spectrometry based determination of polar low molecular weight compounds in dried blood spots.

    PubMed

    Sadones, Nele; Van Bever, Elien; Archer, John R H; Wood, David M; Dargan, Paul I; Van Bortel, Luc; Lambert, Willy E; Stove, Christophe P

    2016-09-23

    Dried blood spot (DBS) sampling and analysis is increasingly being applied in bioanalysis. Although the use of DBS has many advantages, it is also associated with some challenges. E.g. given the limited amount of available material, highly sensitive detection techniques are often required to attain sufficient sensitivity. In gas chromatography coupled to mass spectrometry (GC-MS), derivatization can be helpful to achieve adequate sensitivity. Because this additional sample preparation step is considered as time-consuming, we introduce a new derivatization procedure, i.e. "microwave-assisted on-spot derivatization", to minimize sample preparation of DBS. In this approach the derivatization reagents are directly applied onto the DBS and derivatization takes place in a microwave instead of via conventional heating. In this manuscript we evaluated the applicability of this new concept of derivatization for the determination of two polar low molecular weight molecules, gamma-hydroxybutyric acid (GHB) and gabapentin, in DBS using a standard GC-MS configuration. The method was successfully validated for both compounds, with imprecision and bias values within acceptance criteria (<20% at LLOQ, <15% at 3 other QC levels). Calibration lines were linear over the 10-100μg/mL and 1-30μg/mL range for GHB and gabapentin, respectively. Stability studies revealed no significant decrease of gabapentin and GHB in DBS upon storage at room temperature for at least 84 days. Furthermore, DBS-specific parameters, including hematocrit and volume spotted, were evaluated. As demonstrated by the analysis of GHB and gabapentin positive samples, "microwave-assisted on-spot derivatization" proved to be reliable, fast and applicable in routine toxicology. Moreover, other polar low molecular weight compounds of interest in clinical and/or forensic toxicology, including vigabatrin, beta-hydroxybutyric acid, propylene glycol, diethylene glycol, 1,4-butanediol and 1,2-butanediol, can also be

  10. Field-test of a date-rape drug detection device.

    PubMed

    Quest, Dale W; Horsley, Joanne

    2007-01-01

    Drink Safe Technology Version 1.2 is an inexpensive color-change reagent test marketed internationally for use by consumers in settings such as a night club to detect potentially incapacitating concentrations of gamma-hydroxybutyric acid (GHB) and ketamine in beverages. The objective of this study was to compare product performance in the laboratory and performance in the hands of consumers in the field. Product performance in the laboratory adhered to the protocol defined by the manufacturer. Product performance in the hands of consumers in field settings allowed browsing participants to pipette an aliquot of their own drinks into randomly coded vials containing authentic drugs, or pure water, so as to yield the same concentrations of GHB or ketamine specified in the manufacturer-defined protocol, or blanks. Consumers were to proceed according to the directions printed on the product, and to record their results on a card with a code corresponding with the vial to which they had added an aliquot of their beverage. Diagnostic performance was calculated using two-way analysis. In the laboratory, Drink Safe Technology Version 1.2 reliably detected GHB and ketamine at concentrations specified by the manufacturer's protocol. The reactive color change denoting a positive test for GHB was rapid, but a positive test for ketamine required substantially more time to resolve. Nonetheless, test accuracy following the manufacturer's protocol in the laboratory was 100%. In the field, based on 101 paired-test results recorded by consumers, the test efficiency was 65.1%, sensitivity 50%, and specificity 91.6%. The product performed much better in the laboratory than it did in the hand of consumers in the field. There seems to be considerable potential for consumers to misinterpret a test result. The potential for consumers to record a false-negative test result for a spiked drink is cause for concern.

  11. Boron/Carbon/Silicon/Nitrogen Ceramics And Precursors

    NASA Technical Reports Server (NTRS)

    Riccitiello, Salvatore; Hsu, Ming TA; Chen, Timothy S.

    1996-01-01

    Ceramics containing various amounts of boron, carbon, silicon, and nitrogen made from variety of polymeric precursors. Synthesized in high yield from readily available and relatively inexpensive starting materials. Stable at room temperature; when polymerized, converted to ceramics in high yield. Ceramics resist oxidation and other forms of degradation at high temperatures; used in bulk to form objects or to infiltrate other ceramics to obtain composites having greater resistance to oxidation and high temperatures.

  12. Novel Precursor Approached for CMC Derived by Polymer Pyrolysis

    DTIC Science & Technology

    1994-02-15

    DERIVED BY POLYMER PYROLYSIS Prepared by W. R. Schmidt FINAL TECHNICAL REPORT3 for period 15 Dec 1990 through 14 December 93 Contract F49620-91-C-0017...NOVEL PRECURSOR APPROACHES FOR CMC DERIVED F49620-91-C-0017 BY POLYMER PYROLYSIS 56. AUTHOR(S) Wayde R. Schmidt 7. PERFORMING ORGANIZATION NAME(S) AND...processing and pyrolysis . The conversion of PMVS to carbon-rich nanocrystalline silicon carbide ceramic was studied using a variety- of analytical

  13. Approach to accurately measuring the speed of optical precursors

    SciTech Connect

    Li Chuanfeng; Zhou Zongquan; Guo Guangcan; Jeong, Heejeong

    2011-10-15

    Precursors can serve as a bound on the speed of information with dispersive medium. We propose a method to identify the speed of optical wave fronts using polarization-based interference in a solid-state device, which can bound the accuracy of the speed of wave fronts to less than 10{sup -4} with conventional experimental conditions. Our proposal may have important implications for optical communications and fast information processing.

  14. Synthesis of high phase pure cuprate superconductors via xerogel precursors

    NASA Astrophysics Data System (ADS)

    Macho, J.; Schaeffer, R. W.; Myer, G. H.; Salomon, R. E.; Crow, J. E.

    1992-05-01

    A xerogel method has been developed which is applicable to many superconductor oxides. The method combines the advantages of the freeze drying processing and the sol gel technology without many of the disadvantages, such as long processing times and cost, unstable precursors, and labor intensity. The process is capable of producing high phase purity YBCO ceramic oxide superconducting powders with a particle size smaller than 1 micron.

  15. COS in the stratosphere. [sulfuric acid aerosol precursor

    NASA Technical Reports Server (NTRS)

    Inn, E. C. Y.; Vedder, J. F.; Tyson, B. J.; Ohara, D.

    1979-01-01

    Carbonyl sulfide (COS) has been detected in the stratosphere, and mixing ratio measurements are reported for altitudes of 15.2 to 31.2 km. A large volume, cryogenic sampling system mounted on board a U-2 aircraft has been used for lower stratosphere measurements and a balloon platform for measurement at 31.2 km. These observations and measurements strongly support the concept that stratospheric COS is an important precursor in the formation of sulfuric acid aerosols.

  16. New Ir Bis-Carbonyl Precursor for Water Oxidation Catalysis.

    PubMed

    Huang, Daria L; Beltrán-Suito, Rodrigo; Thomsen, Julianne M; Hashmi, Sara M; Materna, Kelly L; Sheehan, Stafford W; Mercado, Brandon Q; Brudvig, Gary W; Crabtree, Robert H

    2016-03-07

    This paper introduces Ir(I)(CO)2(pyalc) (pyalc = (2-pyridyl)-2-propanoate) as an atom-efficient precursor for Ir-based homogeneous oxidation catalysis. This compound was chosen to simplify analysis of the water oxidation catalyst species formed by the previously reported Cp*Ir(III)(pyalc)OH water oxidation precatalyst. Here, we present a comparative study on the chemical and catalytic properties of these two precursors. Previous studies show that oxidative activation of Cp*Ir-based precursors with NaIO4 results in formation of a blue Ir(IV) species. This activation is concomitant with the loss of the placeholder Cp* ligand which oxidatively degrades to form acetic acid, iodate, and other obligatory byproducts. The activation process requires substantial amounts of primary oxidant, and the degradation products complicate analysis of the resulting Ir(IV) species. The species formed from oxidation of the Ir(CO)2(pyalc) precursor, on the other hand, lacks these degradation products (the CO ligands are easily lost upon oxidation) which allows for more detailed examination of the resulting Ir(pyalc) active species both catalytically and spectroscopically, although complete structural analysis is still elusive. Once Ir(CO)2(pyalc) is activated, the system requires acetic acid or acetate to prevent the formation of nanoparticles. Investigation of the activated bis-carbonyl complex also suggests several Ir(pyalc) isomers may exist in solution. By (1)H NMR, activated Ir(CO)2(pyalc) has fewer isomers than activated Cp*Ir complexes, allowing for advanced characterization. Future research in this direction is expected to contribute to a better structural understanding of the active species. A diol crystallization agent was needed for the structure determination of 3.

  17. [Plant sterols, cholesterol precursors and oxysterols: small amounts, big effects].

    PubMed

    Olkkonen, Vesa M; Gylling, Helena; Ikonen, Elina

    2015-01-01

    Noncholesterol sterols are present in the body in very low concentrations compared with cholesterol. Minor structural changes in sterols give them completely individual biological activities. Steroid hormones are the best known example of this. The knowledge of other relatives of cholesterol, particularly plant sterols, cholesterol precursors and oxysterols, their properties, physiological effects, significance in disease processes and diagnostic applications has recently undergone a rapid increase.

  18. Synthesis of a Precursor to Sacubitril Using Enabling Technologies.

    PubMed

    Lau, Shing-Hing; Bourne, Samuel L; Martin, Benjamin; Schenkel, Berthold; Penn, Gerhard; Ley, Steven V

    2015-11-06

    An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield.

  19. A novel precursor for synthesis of pure boron nitride nanotubes.

    PubMed

    Tang, Chengchun; Bando, Yoshio; Sato, Tadao; Kurashima, Keiji

    2002-06-21

    A novel precursor, a mixture of B2O2 and Mg which is generated in situ by reacting B and MgO at 1300 degrees C, can be used to effectively synthesize bulk amounts of pure BN nanotubes with Mg evaporated from the final product; transmission electron microscope observation for the synthesized BN nanotubes indicates that defects present strongly depend on the tube diameter.

  20. Structural analysis of the precursor pseudogap in cuprate superconductors

    NASA Astrophysics Data System (ADS)

    Suzuki, Sokichi

    2016-10-01

    We investigate the precursor pseudogap (PP) state that emerges on the lower temperature side of the pseudogap phase in cuprate superconductors based on the characteristic layer structure. The coherence among layers in the electronic state may be broken by low energy thermal interactions, whereas the coherence within the layers remains in the phase above the superconducting (SC) phase on account of strongness of the bonding. In this state, the two-electron energy gain (TEG) is also larger than that of SC state and the one-electron energy gain (OEG) is smaller than that of the SC state. We call this incoherent ensemble of in-layer states the in-layer electronic state system (IESS). The PP state is a crossover state between IESS and the normal pseudogap (NP) state, which appears on the upper temperature side, because the d-wave pairing symmetry in cuprates inverts the sign of the difference of the total electronic energy gain between the IESS and the NP state around the nodal region, even though it is positive overall. We perform our analysis at the mean field level. We show that the relationships among the SC gap, the gap of in-layer state, and the transition temperatures in the relevant phases are compatible with existing experimental data. The proposed precursor state requires pairing models to make the SC interactions three-dimensional beyond a single layer, although the precursors have in-layer properties.

  1. Laser synthesis of nanostructured ceramics from liquid precursors

    NASA Astrophysics Data System (ADS)

    Wilden, Johannes; Fischer, Georg

    2007-12-01

    The free-form net shape laser synthesis of nanostructured ceramics from liquid precursors enables a residual stress-free production of high temperature resistant ceramic units and components for the use in microsystem engineering. Due to the use of molecular compounded liquid, ceramic precursors the resulting ceramic components show outstanding properties, for example high purity and a nanostructured material design. The use of pulsed lasers enables a defined input of energy required to pyrolyse the precursor material into a crystalline ceramic, so the active volume can be reduced significantly compared to other processes, for example pyrolysis by furnace. In this paper several methods for a further minimization of the active volume are presented. The investigations determined different factors affecting the process. Realizing selective experiments allows a determination of their influencing level and the definition of a working area to produce three-dimensional components with high aspect ratio. By several studies, e.g., scanning electron microscopy, transmission electron microscopy as well as X-ray diffraction analysis, the atomic structure and composition of the created components were analyzed and valued, so the different reaction processes can be described extensively.

  2. Spinal Cord Neuronal Precursors Generate Multiple Neuronal Phenotypes in Culture

    PubMed Central

    Kalyani, Anjali J.; Piper, David; Mujtaba, Tahmina; Lucero, Mary T.; Rao, Mahendra S.

    2010-01-01

    Neuronal restricted precursors (NRPs) (Mayer-Proschel et al., 1997) can generate multiple neurotransmitter phenotypes during maturation in culture. Undifferentiated E-NCAM+ (embryonic neural cell adhesion molecule) immunoreactive NRPs are mitotically active and electrically immature, and they express only a subset of neuronal markers. Fully mature cells are postmitotic, process-bearing cells that are neurofilament-M and synaptophysin immunoreactive, and they synthesize and respond to different subsets of neurotransmitter molecules. Mature neurons that synthesize and respond to glycine, glutamate, GABA, dopamine, and acetylcholine can be identified by immunocytochemistry, RT-PCR, and calcium imaging in mass cultures. Individual NRPs also generate heterogeneous progeny as assessed by neurotransmitter response and synthesis, demonstrating the multipotent nature of the precursor cells. Differentiation can be modulated by sonic hedgehog (Shh) and bone morphogenetic protein (BMP)-2/4 molecules. Shh acts as a mitogen and inhibits differentiation (including cholinergic differentiation). BMP-2 and BMP-4, in contrast, inhibit cell division and promote differentiation (including cholinergic differentiation). Thus, a single neuronal precursor cell can differentiate into multiple classes of neurons, and this differentiation can be modulated by environmental signals. PMID:9742154

  3. Reduction of precursor decay anomaly in single crystal lithium fluoride

    NASA Astrophysics Data System (ADS)

    Sano, Yukio

    2000-08-01

    The purpose of this study is to reveal that the precursor decay anomaly in single crystal lithium fluoride is reduced by Sano's decay curve [Y. Sano, J. Appl. Phys. 85, 7616 (1999)], which is much smaller in slope than Asay's decay curve [J. R. Asay, G. R. Fowles, G. E. Duvall, M. H. Miles, and R. F. Tinder, J. Appl. Phys. 43, 2132 (1972)]. To this end, strain, particle, velocity, and stress in a precursor and near the leading edge of the follower changing with time along Sano's decay curve are first analyzed quantitatively. The analysis verified the existence of degenerate contraction waves I and II and a subrarefaction wave R', and the decay process [Y. Sano, J. Appl. Phys. 77, 3746 (1995)] caused in sequence by evolving followers C, I, II, R', Rb. Next, inequalities relating decay rates qualitatively to plastic strain rates at the leading edge of the follower, which are derived using the properties of the followers, are incorporated into the analysis. Calculation results showed that the plastic strain rates were reduced by low decay rates. This indicates that the precursor decay anomaly might be greatly reduced by Sano's decay curve.

  4. Observations of Electromagnetic Whistler Precursors at Supercritical Interplanetary Shocks

    NASA Technical Reports Server (NTRS)

    Wilson, L. B., III; Koval, A.; Szabo, Adam; Breneman, A.; Cattell, C. A.; Goetz, K.; Kellogg, P. J.; Kersten, K.; Kasper, J. C.; Maruca, B. A.; Pulupa, M.

    2012-01-01

    We present observations of electromagnetic precursor waves, identified as whistler mode waves, at supercritical interplanetary shocks using the Wind search coil magnetometer. The precursors propagate obliquely with respect to the local magnetic field, shock normal vector, solar wind velocity, and they are not phase standing structures. All are right-hand polarized with respect to the magnetic field (spacecraft frame), and all but one are right-hand polarized with respect to the shock normal vector in the normal incidence frame. They have rest frame frequencies f(sub ci) < f much < f(sub ce) and wave numbers 0.02 approx < k rho (sub ce) approx <. 5.0. Particle distributions show signatures of specularly reflected gyrating ions, which may be a source of free energy for the observed modes. In one event, we simultaneously observe perpendicular ion heating and parallel electron acceleration, consistent with wave heating/acceleration due to these waves. Al though the precursors can have delta B/B(sub o) as large as 2, fluxgate magnetometer measurements show relatively laminar shock transitions in three of the four events.

  5. Ion collisions and the Z-pinch precursor column

    NASA Astrophysics Data System (ADS)

    Sherlock, M.; Chittenden, J. P.; Lebedev, S. V.; Haines, M. G.

    2004-04-01

    During the early stages of a wire array Z-pinch implosion, low density plasma streams toward the axis by virtue of the Lorentz force. This streaming precursor plasma may initially be highly collisionless with respect to ion-ion collisions and therefore cannot be modeled using standard fluid theory. The hybrid method in this paper models both collisional and collisionless behavior with ions exchanging energy and momentum with other ions via a Monte Carlo algorithm equivalent to a small-angle kinetic solution and with an electron fluid via a frictional force. It is shown that the axial stagnation of the plasma flow occurs once the density becomes sufficiently high to initiate a nonlinear rise in electron-ion energy exchange, resulting in the thermal equilibration between radiatively cooling electrons and hot, thermalized ions. This then gives rise to a dense, long-lived precursor column on axis, as observed experimentally. The column is held in place by the kinetic pressure of the streaming precursor plasma, which is balanced by the thermal pressure of the plasma in the column at the column's edge.

  6. Precursor lesions in pancreatic cancer: morphological and molecular pathology.

    PubMed

    Scarlett, Christopher J; Salisbury, Elizabeth L; Biankin, Andrew V; Kench, James

    2011-04-01

    Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.

  7. Oxidation and formation of deposit precursors in hydrocarbon fuels

    NASA Technical Reports Server (NTRS)

    Mayo, F. R.; Lan, B.; Cotts, D. B.; Buttrill, S. E., Jr.; St.john, G. A.

    1983-01-01

    The oxidation of two jet turbine fuels and some pure hydrocarbons was studied at 130 C with and without the presence of small amounts of N-methyl pyrrole (NMP) or indene. Tendency to form solid-deposit precursors was studied by measuring soluble gum formation as well as dimer and trimer formation using field ionization mass spectrometry. Pure n-dodecane oxidized fastest and gave the smallest amount of procursors. An unstable fuel oil oxidized much slower but formed large amounts of precursors. Stable Jet A fuel oxidized slowest and gave little precursors. Indene either retarded or accelerated the oxidation of n-dodecane, depending on its concentration, but always caused more gum formation. The NMP greatly retarded n-dodecane oxidation but accelerated Jet A oxidation and greatly increased the latter's gum formation. In general, the additive reacted faster and formed most of the gum. Results are interpreted in terms of classical cooxidation theory. The effect of oxygen pressure on gum formation is also reported.

  8. Development of techniques for tagging precursor and essential chemicals

    SciTech Connect

    Swansiger, W.A.; Shepodd, T.J.; Phillips, M.L.F.

    1994-01-01

    The ability to identify the manufacturers and distributors of chemicals seized in raids of illicit drug labs would be of great value in controlling the diversion of these chemicals. We developed a tagging scheme based on the addition of sub-ppM concentrations of various combinations of rare-earth elements to the target chemicals and evaluated a number of techniques for detecting the tags. We developed soluble tags for tagging liquids and selected Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) as the preferred detection technique. We developed insoluble tags for tagging solids and developed methods to analyze them and mix them into solid precursors. We have successfully demonstrated the tagging of several solvents and two of the precursor chemicals used in one of the most popular clandestine methamphetamine syntheses (ephedrine reacting with hydriodic acid/red phosphorus). The tagging scheme is capable of yielding tens of thousands of signatures (using holmium as an internal standard and up to 9 rare-earths at up to 3 concentrations yields 3{sup 9} {minus} 1 = 19,682 signatures) and is applicable to most of the chemicals on the precursor and essential chemicals list. In the concentrations employed, the tags are safe enough to be added to pharmaceuticals and cheap enough to tag tanker loads of chemicals.

  9. LWIR hyperspectral imaging application and detection of chemical precursors

    NASA Astrophysics Data System (ADS)

    Lavoie, Hugo; Thériault, Jean-Marc; Bouffard, François; Puckrin, Eldon; Dubé, Denis

    2012-10-01

    Detection and identification of Toxic industrial chemicals (TICs) represent a major challenge to protect and sustain first responder and public security. In this context, passive Hyperspectral Imaging (HSI) is a promising technology for the standoff detection and identification of chemical vapors emanating from a distant location. To investigate this method, the Department of National Defense and Public Safety Canada have mandated Defense Research and Development Canada (DRDC) - Valcartier to develop and test Very Long Wave Infrared (VLWIR) HSI sensors for standoff detection. The initial effort was focused to address the standoff detection and identification of toxic industrial chemicals (TICs), surrogates and precursors. Sensors such as the Improved Compact ATmospheric Sounding Interferometer (iCATSI) and the Multi-option Differential Detection and Imaging Fourier Spectrometer (MoDDIFS) were developed for this application. This paper presents the sensor developments and preliminary results of standoff detection and identification of TICs and precursors. The iCATSI and MoDDIFS sensors are based on the optical differential Fourier-transform infrared (FTIR) radiometric technology and are able to detect, spectrally resolve and identify small leak at ranges in excess of 1 km. Results from a series of trials in asymmetric threat type scenarios are reported. These results serve to establish the potential of passive standoff HSI detection of TICs, precursors and surrogates.

  10. Thermogravimetric evaluation of the suitability of precursors for MOCVD

    NASA Astrophysics Data System (ADS)

    Kunte, G. V.; Shivashankar, S. A.; Umarji, A. M.

    2008-02-01

    A method based on the Langmuir equation for the estimation of vapour pressure and enthalpy of sublimation of subliming compounds is described. The variable temperature thermogravimetric/differential thermogravimetric (TG/DTG) curve of benzoic acid is used to arrive at the instrument parameters. Employing these parameters, the vapour pressure-temperature curves are derived for salicylic acid and camphor from their TG/DTG curves. The values match well with vapour pressure data in the literature, obtained by effusion methods. By employing the Clausius-Clapeyron equation, the enthalpy of sublimation could be calculated. Extending the method further, two precursors for metal-organic chemical vapour deposition (MOCVD) of titanium oxide bis-isopropyl bis tert-butyl 2-oxobutanoato titanium, Ti(OiPr)2(tbob)2, and bis-oxo-bis-tertbutyl 2-oxobutanoato titanium, [TiO(tbob)2]2, have been evaluated. The complex Ti(OiPr)2(tbob)2 is found to be a more suitable precursor. This approach can be helpful in quickly screening for the suitability of a compound as a CVD precursor.

  11. Regulation of phosphatidylserine synthase from Saccharomyces cerevisiae by phospholipid precursors.

    PubMed Central

    Poole, M A; Homann, M J; Bae-Lee, M S; Carman, G M

    1986-01-01

    The addition of ethanolamine or choline to inositol-containing growth medium of Saccharomyces cerevisiae wild-type cells resulted in a reduction of membrane-associated phosphatidylserine synthase (CDPdiacylglycerol:L-serine O-phosphatidyltransferase, EC 2.7.8.8) activity in cell extracts. The reduction of activity did not occur when inositol was absent from the growth medium. Under the growth conditions where a reduction of enzyme activity occurred, there was a corresponding qualitative reduction of enzyme subunit as determined by immunoblotting with antiserum raised against purified phosphatidylserine synthase. Water-soluble phospholipid precursors did not effect purified phosphatidylserine synthase activity. Phosphatidylserine synthase (activity and enzyme subunit) was not regulated by the availability of water-soluble phospholipid precursors in S. cerevisiae VAL2C(YEp CHO1) and the opi1 mutant. VAL2C(YEp CHO1) is a plasmid-bearing strain that over produces phosphatidylserine synthase activity, and the opi1 mutant is an inositol biosynthesis regulatory mutant. The results of this study suggest that the regulation of phosphatidylserine synthase by the availability of phospholipid precursors occurs at the level of enzyme formation and not at the enzyme activity level. Furthermore, the regulation of phosphatidylserine synthase is coupled to inositol synthesis. Images PMID:3023284

  12. Precursors of primary nucleation induced by flow in isotactic polypropylene

    NASA Astrophysics Data System (ADS)

    Somani, Rajesh H.; Yang, Ling; Hsiao, Benjamin S.

    2002-02-01

    Small-angle X-ray scattering (SAXS) patterns of the sheared isotactic polypropylene (i-PP) melt at 175°C, above the nominal melting point of 162°C, showed development of oriented structures or aggregates of polymer molecules that did not disappear even after a long time relaxation (up to 2 h). However, the corresponding wide-angle X-ray diffraction (WAXD) patterns did not show any visible Bragg reflections, suggesting that the induced structures are probably non-crystalline. The results suggest that metastable aggregates of polymer molecules are generated in the melt by assembly of bundle of oriented chain segments (especially in long chains). We speculate that the oriented aggregates of chain segments are precursors of primary nuclei. The spatial arrangement of these precursors showed a layer-like superstructure, evident by the appearance of the meridional maxima in SAXS. The spacing between the ‘layers’ was estimated to be 430 Å. A microstructural model of the orientation-induced precursors for primary nucleation is presented. An Avrami model was used to fit the evolution of the oriented structures in i-PP melt, which provided insights into the early stages of polymer crystallization.

  13. Elastic Precursor Decay in S-200F Beryllium

    NASA Astrophysics Data System (ADS)

    Adams, Chris; Anderson, William; Blumenthal, William; Gray, George (Rusty), III

    2013-06-01

    We have performed a number of plate impact experiments on vacuum hot-pressed (VHP) S-200F Be at shock stresses between 2.1 and 23 GPa to gain insight into the dynamic strength and damage behavior of this technologically important material. In this discussion we will focus on our observations of dynamic strength represented by the Hugoniot Elastic Limit (HEL) determined from the amplitude of the elastic precursor wave observed in VISAR wave profiles collected at the rear surface of the target for experiments conducted in transmission geometry. We observe monotonic decay in precursor amplitude with run distance for sample thicknesses between 4 and 8 mm. We will discuss the observed precursor decay with respect to the relative roles of twinning and dislocation mediated slip in the overall material mechanical response. We will make comparisons with similar data obtained from experiments conducted on roll-textured plate where the contribution of twinning to initial deformation is expected to be suppressed. C. D. Adams et al., ``Shock Compression of Condensed Matter - 2009,'' AIP Conference Proceedings 1195, 1, 509-512 (2009).

  14. Precursor Analysis for Flight- and Ground-Based Anomaly Risk Significance Determination

    NASA Technical Reports Server (NTRS)

    Groen, Frank

    2010-01-01

    This slide presentation reviews the precursor analysis for flight and ground based anomaly risk significance. It includes information on accident precursor analysis, real models vs. models, and probabilistic analysis.

  15. Progressing from identification and functional analysis of precursor behavior to treatment of self-injurious behavior.

    PubMed

    Dracobly, Joseph D; Smith, Richard G

    2012-01-01

    This multiple-study experiment evaluated the utility of assessing and treating severe self-injurious behavior SIB based on the outcomes of a functional analysis of precursor behavior. In Study 1, a precursor to SIB was identified using descriptive assessment and conditional probability analyses. In Study 2, a functional analysis of precursor behavior was conducted. Finally, study 3 evaluated the effects of a treatment in which precursor behavior produced the maintaining variable identified in the precursor functional analysis. Studies 1 and 3 were conducted in two settings in the participants natural environment, where data collection was ongoing throughout the course of the study. Results showed that it was possible to identify a precursor to infrequent but severe SIB, that a functional analysis of precursor behavior suggested a clear operant function, and that treatment based on the results of the precursor functional analysis reduced SIB in the natural environment.

  16. Precursors in the preparation of transition metal nitrides and transition metal carbonitrides and their reaction intermediates

    DOEpatents

    Maya, Leon

    1991-01-01

    A process for making ammonolytic precursors to nitride and carbonitride ceramics. Extreme reaction conditions are not required and the precursor is a powder-like substance that produces ceramics of improved purity and morphology upon pyrolysis.

  17. New Chemical Precursors for the Growth of Ferroelectric and Mid-Valent Metal Oxide Films

    DTIC Science & Technology

    2014-02-20

    SECURITY CLASSIFICATION OF: This proposal seeks to prepare improved chemical vapor deposition (CVD) and atomic layer deposition (ALD) precursors to...P.O. Box 12211 Research Triangle Park, NC 27709-2211 Precursor Synthesis, Inorganic Chemistry, Chemical Vapor Deposition, Atomic Layer Deposition...chemical vapor deposition (CVD) and atomic layer deposition (ALD) precursors to materials that contain Sr, Ba, and Ti and ALD precursors for the mid

  18. Preparation of Bi-Sr-Ca-Cu-O superconductors from oxide-glass precursors

    DOEpatents

    Hinks, David G.; Capone, II, Donald W.

    1992-01-01

    A superconductor and precursor therefor from oxide mixtures of Ca, Sr, Bi and Cu. Glass precursors quenched to elevated temperatures result in glass free of crystalline precipitates having enhanced mechanical properties. Superconductors are formed from the glass precursors by heating in the presence of oxygen to a temperature below the melting point of the glass.

  19. Liquid precursor for deposition of indium selenide and method of preparing the same

    DOEpatents

    Curtis, Calvin J.; Miedaner, Alexander; van Hest, Marinus Franciscus Antonius Maria; Ginley, David S.; Hersh, Peter A.; Eldada, Louay; Stanbery, Billy J.

    2015-09-22

    Liquid precursors containing indium and selenium suitable for deposition on a substrate to form thin films suitable for semiconductor applications are disclosed. Methods of preparing such liquid precursors and method of depositing a liquid precursor on a substrate are also disclosed.

  20. Possibility to study ionospheric earthquakes precursors using CubeSats

    NASA Astrophysics Data System (ADS)

    Korepanov, Valery; Lappas, Vaios

    It is generally accepted that the earthquakes (EQ) are the most dangerous natural phenomena leading to the multiple losses in human lives and economics. The space observations must be included into the global chain of the EQ precursors monitoring at least as the initial warning to pay greater attention to the ground segment data. As the common opinion agrees, only in combination of multiple observation sites and set of monitored parameters the further progress at the way to raise EQ precursors detection probability may be obtained. There is necessary to answer two important questions before to plan any experiment to study ionospheric precursors of EQ. First one - whether the variations in the ionosphere definitely connected with the EQ preparation process do exist, and the second one - if they do, whether using these signals the precursors of EQ can be reliably identified and used for, if not prediction, then for the warning that the EQ in the given area approaches. The first successful mission dedicated to this problem solution was DEMETER (in orbit during more than 6 years from June 2004 until December 2010). The statistics of this study is impressive: altogether, about 9000 EQs with magnitude larger than M = 5.0 and depth lower than 40 km occurred all over the world during the analyzed period. In the result, the conclusion made there suggests that, obviously, there are real perturbations in the ionosphere connected with the seismic activity, but they are rather weak and at the present stage of data processing may be revealed only with the help of statistical analysis. To realize the study of ionospheric precursors, first it is imperative to clarify the mechanism of energy transfer along the chain “lithosphere-atmosphere-ionosphere”. Many hypotheses of such a mechanism exist, from which the mostly supported are fair weather currents (FWC) and atmospheric gravity waves (AGW), both of which have their pros and contras. The following minimal set of physical

  1. Nicotiana benthamiana as a Production Platform for Artemisinin Precursors

    PubMed Central

    van Herpen, Teun W. J. M.; Cankar, Katarina; Nogueira, Marilise; Bosch, Dirk; Bouwmeester, Harro J.; Beekwilder, Jules

    2010-01-01

    Background Production of pharmaceuticals in plants provides an alternative for chemical synthesis, fermentation or natural sources. Nicotiana benthamiana is deployed at commercial scale for production of therapeutic proteins. Here the potential of this plant is explored for rapid production of precursors of artemisinin, a sesquiterpenoid compound that is used for malaria treatment. Methodology/Principal Findings Biosynthetic genes leading to artemisinic acid, a precursor of artemisinin, were combined and expressed in N. benthamiana by agro-infiltration. The first committed precursor of artemisinin, amorpha-4,11-diene, was produced upon infiltration of a construct containing amorpha-4,11-diene synthase, accompanied by 3-hydroxy-3-methylglutaryl-CoA reductase and farnesyl diphosphate synthase. Amorpha-4,11-diene was detected both in extracts and in the headspace of the N. benthamiana leaves. When the amorphadiene oxidase CYP71AV1 was co-infiltrated with the amorphadiene-synthesizing construct, the amorpha-4,11-diene levels strongly decreased, suggesting it was oxidized. Surprisingly, no anticipated oxidation products, such as artemisinic acid, were detected upon GC-MS analysis. However, analysis of leaf extracts with a non-targeted metabolomics approach, using LC-QTOF-MS, revealed the presence of another compound, which was identified as artemisinic acid-12-β-diglucoside. This compound accumulated to 39.5 mg.kg−1 fwt. Apparently the product of the heterologous pathway that was introduced, artemisinic acid, is further metabolized efficiently by glycosyl transferases that are endogenous to N. benthamiana. Conclusion/Significance This work shows that agroinfiltration of N. bentamiana can be used as a model to study the production of sesquiterpenoid pharmaceutical compounds. The interaction between the ectopically introduced pathway and the endogenous metabolism of the plant is discussed. PMID:21151979

  2. Accident Precursor Analysis and Management: Reducing Technological Risk Through Diligence

    NASA Technical Reports Server (NTRS)

    Phimister, James R. (Editor); Bier, Vicki M. (Editor); Kunreuther, Howard C. (Editor)

    2004-01-01

    Almost every year there is at least one technological disaster that highlights the challenge of managing technological risk. On February 1, 2003, the space shuttle Columbia and her crew were lost during reentry into the atmosphere. In the summer of 2003, there was a blackout that left millions of people in the northeast United States without electricity. Forensic analyses, congressional hearings, investigations by scientific boards and panels, and journalistic and academic research have yielded a wealth of information about the events that led up to each disaster, and questions have arisen. Why were the events that led to the accident not recognized as harbingers? Why were risk-reducing steps not taken? This line of questioning is based on the assumption that signals before an accident can and should be recognized. To examine the validity of this assumption, the National Academy of Engineering (NAE) undertook the Accident Precursors Project in February 2003. The project was overseen by a committee of experts from the safety and risk-sciences communities. Rather than examining a single accident or incident, the committee decided to investigate how different organizations anticipate and assess the likelihood of accidents from accident precursors. The project culminated in a workshop held in Washington, D.C., in July 2003. This report includes the papers presented at the workshop, as well as findings and recommendations based on the workshop results and committee discussions. The papers describe precursor strategies in aviation, the chemical industry, health care, nuclear power and security operations. In addition to current practices, they also address some areas for future research.

  3. Radiative precursors driven by converging blast waves in noble gases

    SciTech Connect

    Burdiak, G. C.; Lebedev, S. V.; Harvey-Thompson, A. J.; Swadling, G. F.; Suzuki-Vidal, F.; Hall, G. N.; Khoory, E.; Pickworth, L.; Bland, S. N.; Grouchy, P. de; Skidmore, J.; Suttle, L.; Bennett, M.; Niasse, N. P. L.; Williams, R. J. R.; Blesener, K.; Atoyan, L.; Cahill, A.; Hoyt, C.; Potter, W.; and others

    2014-03-15

    A detailed study of the radiative precursor that develops ahead of converging blast waves in gas-filled cylindrical liner z-pinch experiments is presented. The experiment is capable of magnetically driving 20 km s{sup −1} blast waves through gases of densities of the order 10{sup −5} g cm{sup −3} (see Burdiak et al. [High Energy Density Phys. 9(1), 52–62 (2013)] for a thorough description). Data were collected for Ne, Ar, and Xe gas-fills. The geometry of the setup allows a determination of the plasma parameters both in the precursor and across the shock, along a nominally uniform line of sight that is perpendicular to the propagation of the shock waves. Radiation from the shock was able to excite NeI, ArII, and XeII/XeIII precursor spectral features. It is shown that the combination of interferometry and optical spectroscopy data is inconsistent with upstream plasmas being in LTE. Specifically, electron density gradients do not correspond to any apparent temperature change in the emission spectra. Experimental data are compared to 1D radiation hydrodynamics HELIOS-CR simulations and to PrismSPECT atomic physics calculations to assist in a physical interpretation of the observations. We show that upstream plasma is likely in the process of being radiatively heated and that the emission from a small percentage of ionised atoms within a cool background plasma dominates the emission spectra. Experiments were carried out on the MAGPIE and COBRA pulsed-power facilities at Imperial College London and Cornell University, respectively.

  4. 3′ processing of eukaryotic precursor tRNAs

    PubMed Central

    Maraia, Richard J.; Lamichhane, Tek N.

    2010-01-01

    Biogenesis of eukaryotic tRNAs requires transcription by RNA polymerase III and subsequent processing. 5′ processing of precursor tRNA occurs by a single mechanism, cleavage by RNase P, and usually occurs before 3′ processing although some conditions allow observation of the 3′-first pathway. 3′ processing is relatively complex and is the focus of this review. Precursor RNA 3′ end formation begins with pol III termination generating a variable length 3′ oligo(U) tract that represents an underappreciated and previously unreviewed determinant of processing. Evidence that the pol III-intrinsic 3′ exonuclease activity mediated by Rpc11p affects 3′ oligo(U) length is reviewed. In addition to multiple 3′ nucleases, pre-tRNA processing involves La and Lsm, distinct oligo(U)-binding proteins with proposed chaperone activities. 3′ processing is performed by the endonuclease RNase Z or the exonuclease Rex1p (possibly others) along alternate pathways conditional on La. We review a S. pombe tRNA reporter system that has been used to distinguish two chaperone activities of La protein to its two conserved RNA binding motifs. Pre-tRNAs with structural impairments are degraded by a nuclear surveillance system that mediates polyadenylation by the TRAMP complex followed by 3′ digestion by the nuclear exosome which appears to compete with 3′ processing. We also try to reconcile limited data on pre-tRNA processing and Lsm proteins which largely affects precursors but not mature tRNAs. A pathway is proposed in which 3′ oligo(U) length is a primary determinant of La binding with subsequent steps distinguished by 3′ endo- vs. exo- nucleases, chaperone activities and nuclear surveillance. PMID:21572561

  5. Cloning, expression and processing of the CP2 neuropeptide precursor of Aplysia.

    PubMed

    Vilim, F S; Alexeeva, V; Moroz, L L; Li, L; Moroz, T P; Sweedler, J V; Weiss, K R

    2001-12-01

    The cDNA sequence encoding the CP2 neuropeptide precursor is identified and encodes a single copy of the neuropeptide that is flanked by appropriate processing sites. The distribution of the CP2 precursor mRNA is described and matches the CP2-like immunoreactivity described previously. Single cell RT-PCR independently confirms the presence of CP2 precursor mRNA in selected neurons. MALDI-TOF MS is used to identify additional peptides derived from the CP2 precursor in neuronal somata and nerves, suggesting that the CP2 precursor may give rise to additional bioactive neuropeptides.

  6. Studies of atherosclerosis determinants and precursors during childhood and adolescence*

    PubMed Central

    Tell, G. S.; Tuomilehto, J.; Epstein, F. H.; Strasser, T.

    1986-01-01

    At a Meeting of Investigators on Epidemiological Studies of Atherosclerosis Determinants and Precursors, which was held in Geneva on 7-9 November 1983, representatives from 26 countries reviewed the current status of epidemiological studies in this area. Particular interest was shown in the following determinants of cardiovascular disease: blood pressure, blood lipid levels, body weight, pathological studies, and tobacco use. Working papers on each determinant were prepared, and recommendations were made on areas for research, and on the need for prevention programmes and pathological studies. This article summarizes the work of the meeting. PMID:3490929

  7. Pillarlike Crystals of Pentacene Prepared from Soluble Precursor

    NASA Astrophysics Data System (ADS)

    Murai, Yuki; Misaki, Masahiro; Ishida, Kenji; Ueda, Yasukiyo

    2011-12-01

    Pillarlike crystals of pentacene were fabricated by heat treatment of 13,6-N-sulfinylacetamidopentacene (SAP) thin films prepared from a soluble precursor. As-spun SAP films were composed of a continuous amorphous layer. SAP molecules were converted to pentacene by an elimination reaction by heat treatment at 110 °C. When the SAP film was heat-treated at 170 °C, the pentacene molecules formed pillarlike crystals of uniform height, wherein they took an edge-on orientation with respect to the substrate.

  8. Graphene nanoribbons synthesized from molecular precursor polymerization on Au(110)

    SciTech Connect

    Massimi, Lorenzo; Ourdjini, Oualid; Della Pia, Ada; Mariani, Carlo; Betti, Maria Grazia; Cavaliere, Emanuele; Gavioli, Luca

    2015-06-23

    A spectroscopic study of 10,10-dibromo-9,9 bianthracene (DBBA) molecules deposited on the Au(110) surface is presented, by means of ultraviolet and X-ray photoemission, and X-ray absorption spectroscopy. Through a thermally activated procedure, these molecular precursors polymerize and eventually form graphene nanoribbons (GNRs) with atomically controlled shape and width, very important building blocks for several technological applications. The GNRs observed by scanning tunneling microscopy (STM) appear as short segments on top of the gold surface reconstruction, pointing out the delicate balance among surface diffusion and surface corrugation in their synthesis on the Au(110) surface.

  9. Selective Manipulation of Microscopic Particles with Precursor Swirling Rayleigh Waves

    NASA Astrophysics Data System (ADS)

    Riaud, Antoine; Baudoin, Michael; Bou Matar, Olivier; Becerra, Loic; Thomas, Jean-Louis

    2017-02-01

    Contactless manipulation of microparticles is demonstrated with single-beam acoustical tweezers based on precursor swirling Rayleigh waves. These surface waves degenerate into acoustical vortices when crossing a stack made of a fluid layer and its solid support, hence creating a localized acoustical trap in a fluid cavity. They can be synthesized with a single interdigitated transducer whose spiraling shape encodes the phase of the field like a hologram. For applications, these tweezers have many attractive features: they are selective, flat, easily integrable, and compatible with disposable substrates.

  10. Polymer precursors for SiC ceramic materials

    NASA Technical Reports Server (NTRS)

    Litt, Morton H.

    1986-01-01

    Work on precursor polymers to SiC was performed, concentrating on polymers made from decamethyl cyclohexasilyene units. The initial approach was to synthesize mixed diphenyl decamethyl cyclohexasilane, dephenylate, and polymerize. This produced polymers which had yields of up to 50 percent SiC. (Theoretical yield is 75 percent). The present approach is to make the polymer through the intermediate trans-1,4-diphenyl decamethyl cyclohexasilane. This should produce a crystalline polymer and high strength fibers. These will be thermally decomposed to SiC fibers. This requires new chemistry which is currently being studied.

  11. Endophytic fungi as a source of biofuel precursors.

    PubMed

    Santos-Fo, Florisvaldo; Fill, Taicia Pacheco; Nakamura, Joanita; Monteiro, Marcos Roberto; Rodrigues-Fo, Edson

    2011-07-01

    Endophytic fungi, isolated from a number of different species of tropical plants, were investigated for lipid biodiesel precursor production. The extracts produced from liquid cultures of these fungi were subjected to acidcatalyzed transesterification reactions with methanol producing methyl esters and then analyzed through chromatographic (GC-FID) and spectrometric techniques (MS, NMR ¹H). The European Standard Method, EN 14103, was used for the quantification of methyl esters extracted from the fungi of the species and genera studied. Xylariaceous fungi exhibited the highest concentrations of methyl esters (91%), and hence may be a promising source for biofuel.

  12. Beryllium-10 in Australasian tektites - Evidence for a sedimentary precursor

    NASA Technical Reports Server (NTRS)

    Pal, D. K.; Moniot, R. K.; Kruse, T. H.; Herzog, G. F.; Tuniz, C.

    1982-01-01

    Each of seven Australasian tektites contains about 100 micron atoms of beryllium-10 (half-life, 1.53 million years) per gram. Cosmic-ray bombardment of the australites cannot have produced the measured amounts of beryllium-10 either at the earth's surface or in space. The beryllium-10 contents of these australites are consistent with a sedimentary precursor that adsorbed from precipitation beryllium-10 produced in the atmosphere. The sediments must have spent several thousand years at the earth's surface within a few million years of the tektite-producing event.

  13. Anomalous astronomical time-latitude residuals: a potential earthquake precursor

    NASA Astrophysics Data System (ADS)

    Hu, Hui; Su, You-Jin; Gao, Yi-Fei; Wang, Rui

    2016-09-01

    The geophysical mechanism behind astronomical time-latitude residuals (ATLR) are discussed. The photoelectric astrolabe at Yunnan Observatory (YO) observed apparent synchronous anomalous ATLR before the Wenchuan M8.0 earthquake (EQ) in May 12, 2008 and the Lushan M7.0 EQ n April 20, 2013. We compared the ATLR from the YO photoelectric astrolabe and EQ data since 1976. Anomalous ATLR was observed before several strong EQs in the Yunnan Province. We believe the photoelectric astrolabe can be used to predict strong EQs and the anomalous ATLR are a potential EQ precursor.

  14. Structural comparison of nickel electrodes and precursor phases

    NASA Technical Reports Server (NTRS)

    Cornilsen, Bahne C.; Shan, Xiaoyin; Loyselle, Patricia

    1989-01-01

    Researchers summarize previous Raman spectroscopic results and discuss important structural differences in the various phases of active mass and active mass precursors. Raman spectra provide unique signatures for these phases, and allow one to distinguish each phase, even when the compound is amorphous to x rays (i.e., does not scatter x rays because of a lack of order and/or small particle size). The structural changes incurred during formation, charge and discharge, cobalt addition, and aging are discussed. The oxidation states and dopant contents are explained in terms of the nonstoichiometric structures.

  15. Survey of volatile oxylipins and their biosynthetic precursors in bryophytes.

    PubMed

    Croisier, Emmanuel; Rempt, Martin; Pohnert, Georg

    2010-04-01

    Oxylipins are metabolites which are derived from the oxidative fragmentation of polyunsaturated fatty acids. These metabolites play central roles in plant hormonal regulation and defense. Here we survey the production of volatile oxylipins in bryophytes and report the production of a high structural variety of C5, C6, C8 and C9 volatiles of mosses. In liverworts and hornworts oxylipin production was not as pronounced as in the 23 screened mosses. A biosynthetic investigation revealed that both, C18 and C20 fatty acids serve as precursors for the volatile oxylipins that are mainly produced after mechanical wounding of the green tissue of mosses.

  16. Gelcasting polymeric precursors for producing net-shaped graphites

    DOEpatents

    Klett, James W.; Janney, Mark A.

    2005-02-15

    The present invention discloses a method for molding complex and intricately shaped high density monolithic carbon, carbon-carbon, graphite, and thermoplastic composites using gelcasting technology. The method comprising a polymeric carbon precursor, a solvent, a dispersant, an anti-foaming agent, a monomer system, and an initiator system. The components are combined to form a suspension which is poured into a mold and heat-treated to form a thermoplastic part. The thermoplastic part can then be further densified and heat-treated to produce a high density carbon or graphite composite. The present invention also discloses the products derived from this method.

  17. Gelcasting polymeric precursors for producing net-shaped graphites

    DOEpatents

    Klett, James W.; Janney, Mark A.

    2002-01-01

    The present invention discloses a method for molding complex and intricately shaped high density monolithic carbon, carbon-carbon, graphite, and thermoplastic composites using gelcasting technology. The method comprising a polymeric carbon precursor, a solvent, a dispersant, an anti-foaming agent, a monomer system, and an initiator system. The components are combined to form a suspension which is poured into a mold and heat-treated to form a thermoplastic part. The thermoplastic part can then be further densified and heat-treated to produce a high density carbon or graphite composite. The present invention also discloses the products derived from this method.

  18. New {beta}-delayed proton precursor {sup 121}Ce

    SciTech Connect

    Zhankui, L.; Shuwei, X.; Yuanxiang, X.; Ruichang, M.; Yuanxiu, G.; Chunfang, W.; Wenxue, H.; Tianmei, Z.

    1997-08-01

    The new {beta}-delayed proton precursor {sup 121}Ce was synthesized in the reaction {sup 92}Mo({sup 32}S,3n) and first identified in p-{gamma}(X) coincidence measurements with a helium-jet recoil fast-moving tape-transport system. The half-life of the {sup 121}Ce decay was determined to be 1.1{plus_minus}0.1 s. Its {beta}-delayed proton spectrum was observed and the {beta}-delayed proton branching ratio for {sup 121}Ce decay was estimated to be {approximately}1{percent}. {copyright} {ital 1997} {ital The American Physical Society}

  19. Ozone precursors have regionally variable effect on radiative forcing

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2013-02-01

    When released near the surface, carbon monoxide, assorted nitrogen oxides (NOx ), and nonmethane hydrocarbons (NMHC) contribute to the production of ozone, a key component of photochemical smog, which is known to have serious deleterious effects on human health. However, when ozone gets lifted into the troposphere, it is a greenhouse gas. That these ozone precursors have such a dual-pronged effect—affecting both human health and the global radiation budget—suggests that mitigating their emissions could be a potential method to both improve air quality and dampen the rate of anthropogenic climate change.

  20. Synthesis of carbon nanotubes using natural carbon precursor: Castor oil

    NASA Astrophysics Data System (ADS)

    Raziah, A. Z.; Junizah, A. R.; Saifuddin, N.

    2012-09-01

    Castor oil has long been an article of commerce due to its versatility as it is widely used as a starting material for many industrial chemical products because of its unique structure. In this study, carbon nanotubes has been synthesized by thermal decomposition of castor oil in nitrogen atmosphere at 300-400δC using custom-made microwave processing unit. The precursor material was catalyzed by iron clusters originating from the addition of ferrocene. The morphology and characterization of the CNTs were studied and discussed by transmission electron microscopy (TEM).

  1. A Brief Up-Date of the Use of Sodium Oxybate for the Treatment of Alcohol Use Disorder

    PubMed Central

    Caputo, Fabio; Vignoli, Teo; Tarli, Claudia; Domenicali, Marco; Zoli, Giorgio; Bernardi, Mauro; Addolorato, Giovanni

    2016-01-01

    The treatment of alcohol use disorder (AUD) with sodium oxybate (SMO) or gamma-hydroxybutyric acid (GHB) was introduced in Italy and Austria more than 20 years and 15 years ago, respectively, and it is now widely employed to treat alcohol withdrawal syndrome (AWS) and to maintain alcohol abstinence. These indications derive from its similar structure to the inhibitory neurotransmitter γ-amino-butyric acid (GABA), exerting an ethanol-mimicking effect, because it binds to GABAB receptors. Craving for, and abuse of, SMO remain a controversial issue; even though these unfavorable effects are evident in poly-drug addicted patients and in those with psychiatric diagnosis of borderline personality disorder. In addition, despite cases of severe intoxication and deaths being widely documented when GHB is used as “street drug”; its clinical use remains safe. Thus, the aim of the present review is to examine the role of SMO in the treatment of AUD, its possible implications in reducing alcohol consumption, and cases of abuse, and severe intoxication due to SMO during its clinical use in the treatment of AUD. PMID:26959045

  2. Functional analysis of precursors for serious problem behavior and related intervention.

    PubMed

    Langdon, Nancy A; Carr, Edward G; Owen-Deschryver, Jamie S

    2008-11-01

    Precursor behaviors are innocuous behaviors that reliably precede the occurrence of problem behavior. Intervention efforts applied to precursors might prevent the occurrence of severe problem behavior. We examined the relationship between precursor behavior and problem behavior in three individuals with developmental disabilities. First, a descriptive (correlational) assessment focusing on transitional probabilities, which established that problem behavior typically followed precursor behavior, was conducted. Next, a functional (experimental) analysis was conducted to evaluate the relationship between precursor and problem behavior. Results suggested that these two behaviors served the same function. Finally, in the intervention phase, participants were taught a response that was functionally equivalent to the precursor behavior. Results demonstrated a decrease in the frequency of problem behavior. Collectively, these results suggest that prevention efforts might profitably be focused on precursor behavior. Further implications for the use of functional analysis and functional communication training in prevention are discussed.

  3. Strain-induced dimensionality crossover of precursor modulations in Ni2MnGa

    SciTech Connect

    Nie, Zhihua; Wang, Yandong; Shang, Shunli; Zeng, Qiaoshi; Ren, Yang; Liu, Dongmei; Yang, Wenge; Wang, Yi; Liu, Zi-Kui

    2015-01-01

    Precursor modulations often occur in functional materials like magnetic shape memory alloys, ferroelectrics, and superconductors. In this letter, we have revealed the underlying mechanism of the precursor modulations in ferromagnetic shape memory alloys Ni2MnGa by combining synchrotron-based x-ray diffraction experiments and first-principles phonon calculations. We discovered the precursor modulations along [011] direction can be eliminated with [001] uniaxial loading, while the precursor modulations or premartensite can be totally suppressed by hydrostatic pressure condition. The TA2 phonon anomaly is sensitive to stress induced lattice strain, and the entire TA2 branch is stabilized along the directions where precursor modulations are eliminated by external stress. Our discovery bridges precursor modulations and phonon anomalies, and sheds light on the microscopic mechanism of the two-step superelasticity in precursor martensite.

  4. Aroma Precursors in Grapes and Wine: Flavor Release during Wine Production and Consumption.

    PubMed

    Parker, Mango; Capone, Dimitra L; Francis, I Leigh; Herderich, Markus J

    2017-03-08

    Pioneering investigations into precursors of fruity and floral flavors established the importance of terpenoid and C13-norisoprenoid glycosides to the flavor of aromatic wines. Nowadays flavor precursors in grapes and wine are known to be structurally diverse, encompassing glycosides, amino acid conjugates, odorless volatiles, hydroxycinnamic acids, and many others. Flavor precursors mainly originate in the grape berry but also from oak or other materials involved in winemaking. Flavors are released from precursors during crushing and subsequent production steps by enzymatic and nonenzymatic transformations, via microbial glycosidases, esterases, C-S lyases, and decarboxylases, and through acid-catalyzed hydrolysis and chemical rearrangements. Flavors can also be liberated from glycosides and amino acid conjugates by oral microbiota. Hence, it is increasingly likely that flavor precursors contribute to retronasal aroma formation through in-mouth release during consumption, prompting a shift in focus from identifying aroma precursors in grapes to understanding aroma precursors present in bottled wine.

  5. Methods of making copper selenium precursor compositions with a targeted copper selenide content and precursor compositions and thin films resulting therefrom

    DOEpatents

    Curtis, Calvin J.; Miedaner, Alexander; van Hest, Marinus Franciscus Antonius Maria; Ginley, David S.; Leisch, Jennifer; Taylor, Matthew; Stanbery, Billy J.

    2011-09-20

    Precursor compositions containing copper and selenium suitable for deposition on a substrate to form thin films suitable for semi-conductor applications. Methods of forming the precursor compositions using primary amine solvents and methods of forming the thin films wherein the selection of temperature and duration of heating controls the formation of a targeted species of copper selenide.

  6. Precursors of deep moist convection in a subkilometer global simulation

    NASA Astrophysics Data System (ADS)

    Miyamoto, Yoshiaki; Yamaura, Tsuyoshi; Yoshida, Ryuji; Yashiro, Hisashi; Tomita, Hirofumi; Kajikawa, Yoshiyuki

    2016-10-01

    Deep moist convection in the atmosphere plays an important role in cloudy weather disturbances, such as hurricanes, and even in the global climate. The convection often causes disastrous heavy rainfall, and predicting such convection is therefore critical for both disaster prevention and climate projection. Although the key parameters for convection have been pointed out, understanding the preprocesses of convection is a challenging issue. Here we identified the precursors of convection by analyzing a global simulated data set with very high resolution in time and space. We found that the mass convergence near the Earth's surface changed significantly several minutes before the initiation of early convection (the formation of cumulus clouds), which occurred with the increase in the convective available potential energy (CAPE). Decomposition of the statistical data revealed that a higher-CAPE environment resulted in stronger convection than in the stronger-convergence case. Furthermore, for the stronger-convergence case, the precursor was detected earlier than the total average (10-15 min before the initiation), whereas the amplitude of maximum velocity was not so strong as the higher-CAPE case. This suggests that the strength of convection is connected with CAPE, and the predictability is sensitive to the convergence.

  7. Synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.

    PubMed

    Abada, Zahra; Cojean, Sandrine; Pomel, Sébastien; Ferrié, Laurent; Akagah, Bernardin; Lormier, Anh Tuan; Loiseau, Philippe M; Figadère, Bruno

    2013-09-01

    Importance of heme in African trypanosomes, Leishmania sp. and Plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. Consequently, twenty-four porphyrin precursors and derivatives were evaluated against Leishmania donovani, Trypanosoma brucei and Plasmodium sp. The best active compound against Trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, with a MEC value of 6.25 μM justifying further in vivo evaluation. Whereas these compounds were not active against intramacrophage amastigotes of L. donovani, another new porphyrin derivative, compound 4f was active in vitro against Plasmodium falciparum at 20 nM and a slight delay of mice survival was observed on the Plasmodium berghei/Swiss mice model at 50 μmol/kg/day × 4. Pharmacomodulations should be further developed relying on a better knowledge on the porphyrin behaviour into the parasites comparatively to host cells.

  8. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

    PubMed Central

    Krautler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L.; Tallquist, Michelle; Buch, Thorsten; Oliveira-Martins, José B.; Zhu, Caihong; Hermann, Mario; Wagner, Ulrich; Brink, Robert; Heikenwalder, Mathias; Aguzzi, Adriano

    2013-01-01

    Summary The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ+-derived cells abolished FDC, indicating that FDC originate from PDGFRβ+ cells. Lymphotoxin-α-overexpressing prion protein (PrP)+ kidneys developed PrP+ FDC after transplantation into PrP mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ+ stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR) kidney capsules, differentiated into Mfge8+CD21/35+ FcγRIIβ+PrP+ FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ+ FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. PMID:22770220

  9. High-quality CdTe films from nanoparticle precursors

    SciTech Connect

    Schulz, D.L.; Pehnt, M.; Urgiles, E.

    1996-05-01

    In this paper the authors demonstrate that nanoparticulate precursors coupled with spray deposition offers an attractive route into electronic materials with improved smoothness, density, and lower processing temperatures. Employing a metathesis approach, cadmium iodide was reacted with sodium telluride in methanol solvent, resulting in the formation of soluble NaI and insoluble CdTe nanoparticles. After appropriate chemical workup, methanol-capped CdTe colloids were isolated. CdTe thin film formation was achieved by spray depositing the nanoparticle colloids (25-75 {Angstrom} diameter) onto substrates at elevated temperatures (T = 280-440{degrees}C) with no further thermal treatment. These films were characterized by x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Cubic CdTe phase formation was observed by XRD, with a contaminant oxide phase also detected. XPS analysis showed that CdTe films produced by this one-step method contained no Na or C and substantial O. AFM gave CdTe grain sizes of {approx}0.1-0.3 {mu}m for film sprayed at 400{degrees}C. A layer-by-layer film growth mechanism proposed for the one-step spray deposition of nanoparticle precursors will be discussed.

  10. Novel drug delivery strategies for porphyrins and porphyrin precursors

    NASA Astrophysics Data System (ADS)

    Morrow, D. I. J.; Donnelly, R. F.

    2009-06-01

    superficial lesions, such as actinic keratosis. In addition, photodynamic antimicrobial chemotherapy (PACT) is attracting increasing interest for the treatment of infection. However, delivery strategies for topical PDT and PACT are still based on application of rather simplistic cream and solution formulations, with little consideration given to thermodynamics, targeting or the physicochemical properties of the active agent. Purpose-designed dosage forms for topical delivery of aminolevulinic acid or its esters include creams containing penetration enhancers and/or iron chelators, pressure sensitive patches and bioadhesive patches. Such systems aim to enhance drug delivery across the stratum corneum and keratinised debris overlying neoplastic lesions and improve subsequent protoporphyrin IX (PpIX) production. The alternative to using porphyrin precursors is the use of pre-formed photosensitisers. However, owing to their relatively high molecular weights, conventional topical application is not appropriate. Innovative strategies, such as the use of needle-free injections and microneedle arrays, bypass the stratum corneum, enabling rapid and targeted delivery not only porphyrin precursors but also pre-formed photosensitisers. This presentation will review drug delivery work published to date in the fields of PDT and PACT. In addition, the benefits of employing the latest advances in pharmaceutical technology will be highlighted.

  11. Precursor solitons in a flowing complex (dusty) plasma

    NASA Astrophysics Data System (ADS)

    Jaiswal, Surabhi; Bandyopadhyay, Pintu; Sen, Abhijit

    2016-10-01

    We report the first experimental observation of precursor solitons in a flowing dusty plasma. The nonlinear solitary dust acoustic waves (DAWs) are excited by a supersonic mass flow of the dust particles passing over an electrostatic potential hill. In a frame where the fluid is stationary and the hill is moving the solitons propagate in the upstream direction while wake structures consisting of linear DAWs are seen to propagate in the downstream direction. The experiments have been carried out in a Π-shaped Dusty Plasma Experimental (DPEx) device where kaolin particles are immersed in a DC discharge argon plasma to form the dusty plasma and a floating wire mounted on the cathode creates a potential hill. The dust flow is induced by sudden changes in the hill height and the solitary structures are seen only for supersonic flows and up to an upper limit of the flow. A theoretical model description of the phenomenon will be provided and some practical implications of such precursor excitations for a charged object moving in a plasma will be discussed.

  12. Advanced accident sequence precursor analysis level 2 models

    SciTech Connect

    Galyean, W.J.; Brownson, D.A.; Rempe, J.L.

    1996-03-01

    The U.S. Nuclear Regulatory Commission Accident Sequence Precursor program pursues the ultimate objective of performing risk significant evaluations on operational events (precursors) occurring in commercial nuclear power plants. To achieve this objective, the Office of Nuclear Regulatory Research is supporting the development of simple probabilistic risk assessment models for all commercial nuclear power plants (NPP) in the U.S. Presently, only simple Level 1 plant models have been developed which estimate core damage frequencies. In order to provide a true risk perspective, the consequences associated with postulated core damage accidents also need to be considered. With the objective of performing risk evaluations in an integrated and consistent manner, a linked event tree approach which propagates the front end results to back end was developed. This approach utilizes simple plant models that analyze the response of the NPP containment structure in the context of a core damage accident, estimate the magnitude and timing of a radioactive release to the environment, and calculate the consequences for a given release. Detailed models and results from previous studies, such as the NUREG-1150 study, are used to quantify these simple models. These simple models are then linked to the existing Level 1 models, and are evaluated using the SAPHIRE code. To demonstrate the approach, prototypic models have been developed for a boiling water reactor, Peach Bottom, and a pressurized water reactor, Zion.

  13. Over-the-Horizon Anomalous VHF Propagation and Earthquake Precursors

    NASA Astrophysics Data System (ADS)

    Devi, M.; Barbara, A. K.; Ruzhin, Ya. Yu.; Hayakawa, M.

    2012-09-01

    The purpose of this paper is to review current activities for the identification of earthquake (EQ) precursors and their epicentres. Starting with a brief description on the background to approaches using ultra-low (ULF), extremely low (ELF), very low/low (VLF/LF), medium (MF), high (HF), very high frequency (VHF) etc. radio waves for short-term EQ prediction, the paper concentrates on those characteristics of anomalous VHF reception from frequency-modulation (FM) radio transmissions and broadcast television (TV) signals in relation to EQ precursors. The possible ways to identify an impending EQ and its epicentre position as defined and observed by workers from a variety of studies fall within the purview of the paper. In attempts to find pre-EQ energy exchange and coupling processes between the lithosphere and atmosphere, the paper highlights some relevant observations of surface latent heat flux, sonic detection and ranging (SODAR) echograms and LF propagation. Explanations on possible causes leading to such anomalous reception are reviewed with reported results in association with pre-seismic induced modifications to tropospheric and ionospheric parameters.

  14. Optimal precursors of different types of ENSO events

    NASA Astrophysics Data System (ADS)

    Capotondi, Antonietta; Sardeshmukh, Prashant D.

    2015-11-01

    Not all El Niño-Southern Oscillation (ENSO) events are the same. Their global impacts can differ substantially depending on whether the associated sea surface temperature (SST) anomalies are stronger in the central Pacific (CP) or the eastern Pacific (EP). The predictability of such differences is therefore of interest. In this study, the optimal two-season precursors of different ENSO types are investigated in a linear inverse modeling framework using observational SST and thermocline depth data for 1958-2007. It is shown that different SST precursor types alone do not favor the generation of different ENSO types. However, initial subsurface conditions characterized by a deeper thermocline in the eastern Pacific and a shallower thermocline in the central Pacific favor the generation of EP-type events, while a shallower thermocline in the east and a deeper thermocline in the central/western Pacific are conducive to CP-type events. The predictability of different ENSO types thus depends importantly on initial subsurface conditions.

  15. Soot precursor measurements in benzene and hexane diffusion flames

    SciTech Connect

    Kobayashi, Y.; Furuhata, T.; Amagai, K.; Arai, M.

    2008-08-15

    To clarify the mechanism of soot formation in diffusion flames of liquid fuels, measurements of soot and its precursors were carried out. Sooting diffusion flames formed by a small pool combustion equipment system were used for this purpose. Benzene and hexane were used as typical aromatic and paraffin fuels. A laser-induced fluorescence (LIF) method was used to obtain spatial distributions of polycyclic aromatic hydrocarbons (PAHs), which are considered as soot particles. Spatial distributions of soot in test flames were measured by a laser-induced incandescence (LII) method. Soot diameter was estimated from the temporal change of LII intensity. A region of transition from PAHs to soot was defined from the results of LIF and LII. Flame temperatures, PAH species, and soot diameters in this transition region were investigated for both benzene and hexane flames. The results show that though the flame structures of benzene and hexane were different, the temperature in the PAHs-soot transition region of the benzene flame was similar to that of the hexane flame. Furthermore, the relationship between the PAH concentrations measured by gas chromatography in both flames and the PAH distributions obtained from LIF are discussed. It was found that PAHs with smaller molecular mass, such as benzene and toluene, remained in both the PAHs-soot transition and sooting regions, and it is thought that molecules heavier than pyrene are the leading candidates for soot precursor formation. (author)

  16. An Accident Precursor Analysis Process Tailored for NASA Space Systems

    NASA Technical Reports Server (NTRS)

    Groen, Frank; Stamatelatos, Michael; Dezfuli, Homayoon; Maggio, Gaspare

    2010-01-01

    Accident Precursor Analysis (APA) serves as the bridge between existing risk modeling activities, which are often based on historical or generic failure statistics, and system anomalies, which provide crucial information about the failure mechanisms that are actually operative in the system and which may differ in frequency or type from those in the various models. These discrepancies between the models (perceived risk) and the system (actual risk) provide the leading indication of an underappreciated risk. This paper presents an APA process developed specifically for NASA Earth-to-Orbit space systems. The purpose of the process is to identify and characterize potential sources of system risk as evidenced by anomalous events which, although not necessarily presenting an immediate safety impact, may indicate that an unknown or insufficiently understood risk-significant condition exists in the system. Such anomalous events are considered accident precursors because they signal the potential for severe consequences that may occur in the future, due to causes that are discernible from their occurrence today. Their early identification allows them to be integrated into the overall system risk model used to intbrm decisions relating to safety.

  17. Radon anomaly in soil gas as an earthquake precursor.

    PubMed

    Miklavcić, I; Radolić, V; Vuković, B; Poje, M; Varga, M; Stanić, D; Planinić, J

    2008-10-01

    The mechanical processes of earthquake preparation are always accompanied by deformations; afterwards, the complex short- or long-term precursory phenomena can appear. Anomalies of radon concentrations in soil gas are registered a few weeks or months before many earthquakes. Radon concentrations in soil gas were continuously measured by the LR-115 nuclear track detectors at site A (Osijek) during a 4-year period, as well as by the Barasol semiconductor detector at site B (Kasina) during 2 years. We investigated the influence of the meteorological parameters on the temporal radon variations, and we determined the equation of the multiple regression that enabled the reduction (deconvolution) of the radon variation caused by the barometric pressure, rainfall and temperature. The pre-earthquake radon anomalies at site A indicated 46% of the seismic events, on criterion M>or=3, R<200 km, and 21% at site B. Empirical equations between earthquake magnitude, epicenter distance and precursor time enabled estimation or prediction of an earthquake that will rise at the epicenter distance R from the monitoring site in expecting precursor time T.

  18. Characterization of haloacetic acid precursors in source water.

    PubMed

    Kanokkantapong, Vorapot; Marhaba, Taha F; Pavasant, Prasert; Panyapinyophol, Bunyarit

    2006-08-01

    Raw water from the Bangkok (Thailand) main municipal water supply canal was examined for its natural organic composition by fractionation with adsorption resins. DAX-8 resin was the first resin employed to fractionate the hydrophobic fractions. Fractionation at neutral pH resulted in the separation of the hydrophobic neutral components; at a high pH level (approx. 10) separation of the hydrophobic base components occurred; and at a low pH level (approx. 2) the hydrophobic acid components were separated. AG-MP-50 cationic resin was then used to separate the hydrophilic base components, and WA-10, a weak anionic resin, was applied finally to fractionate the hydrophilic acid and neutral components. Subsequently, each fraction was tested for its chlorine disinfection by-product (DBP) formation potential. The HAA formation tests demonstrated that the various organic fractions had different reactivity levels for the formation of haloacetic acids (HAAs). For this source water, the hydrophilic neutral fraction dominated over the other five fractions in being the main organic component and the most significant precursor of HAAs formation. On the other hand, in terms of specific HAA formation potential (FP), the hydrophobic and hydrophilic base fractions were the most reactive precursors to the formation of HAAs. In all cases, the quantity of HAAs formed depended linearly upon the amount of organic constituents in the water sample.

  19. Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro

    PubMed Central

    1995-01-01

    The amyloid precursor protein (APP) is a transmembrane protein expressed in several cell types. In the nervous system, APP is expressed by glial and neuronal cells, and several lines of evidence suggest that it plays a role in normal and pathological phenomena. To address the question of the actual function of APP in normal developing neurons, we undertook a study aimed at blocking APP expression using antisense oligonucleotides. Oligonucleotide internalization was achieved by linking them to a vector peptide that translocates through biological membranes. This original technique, which is very efficient and gives direct access to the cell cytosol and nucleus, allowed us to work with extracellular oligonucleotide concentrations between 40 and 200 nM. Internalization of antisense oligonucleotides overlapping the origin of translation resulted in a marked but transient decrease in APP neosynthesis that was not observed with the vector peptide alone, or with sense oligonucleotides. Although transient, the decrease in APP neosynthesis was sufficient to provoke a distinct decrease in axon and dendrite outgrowth by embryonic cortical neurons developing in vitro. The latter decrease was not accompanied by changes in the spreading of the cell bodies. A single exposure to coupled antisense oligonucleotides at the onset of the culture was sufficient to produce significant morphological effects 6, 18, and 24 h later, but by 42 h, there were no remaining significant morphologic changes. This report thus demonstrates that amyloid precursor protein plays an important function in the morphological differentiation of cortical neurons in primary culture. PMID:7876315

  20. Synthetic, characterization and decomposition studies of indium sulfide precursors

    SciTech Connect

    Schluter, R.D.; Luten, H.A.; Rees, W.S. Jr.

    1996-12-31

    The synthesis, characterization and decomposition of several indium thiolates containing the bulky substituted aryl ligand 2,4,6-i-Pr{sub 3}C{sub 6}H{sub 2} (Ar{prime}) or the internally chelating ligands 2-CH{sub 3}O, 5-CH{sub 3}C{sub 6}H{sub 3} (Ar{double_prime}) and o-C{sub 6}H{sub 4}CH{sub 2}N(CH{sub 3}){sub 2} (Ar{prime}{double_prime}) are described. Two synthetic methods have been utilized: metathesis reactions between lithium thiolates and the appropriate metal halides and the addition of elemental metal to diaryl disulfides. The thermal decomposition of each indium precursor results in the formation of In{sub 2}S{sub 3}, based on thermogravimetric data. The homoleptic compound In(SAr{prime}){sub 3} can be isolated as a yellow oil. This liquid precursor has been derivatized by the reversible formation of acetonitrile and tetrahydroduran adducts. Although, the molecule exists as a monomer in both adducts, the coordination number of the metal and the orientation of the ligands are markedly different. The internally chelating In(SAr{double_prime}){sub 3} and In(SAr{prime}{double_prime}){sub 3} adopt contrasting dimeric and monomeric structures respectively.

  1. Unimolecular precursors to binary metal sulfides: Mechanistic and structural correlations

    SciTech Connect

    Schluter, R.D.; Kraeuter, G.; Rees, W.S. Jr.

    1996-12-31

    The roles which ligand size and stability play in influencing solid-state thermolyses products and phases are developed for a group of metal thiolate compounds. The exploration includes Pb(SR){sub 2} [R = t-Bu, i-Bu, s-Bu], Cd(SR*){sub 2} [R* = i-Pr, t-Bu, Bz], ClHgSR** [R** = i-Pr, neo-Pent, Bz] and In(SR***){sub 3} [R*** = 2,4,6-(i-Pr){sub 3}C{sub 6}H{sub 2}, 2-CH{sub 3}O-5-CH{sub 3}C{sub 6}H{sub 3}, o-C{sub 6}H{sub 4}CH{sub 2}N(CH{sub 3}){sub 2}]. In several examples, the precursors have been characterized by single crystal X-ray diffraction. In most cases, solid-state decomposition products have been identified by XRPD, and volatile decomposition products have been identified by GC/MS. All precursors have been studied by TGA.

  2. Preparation of plutonium-bearing ceramics via mechanically activated precursor

    NASA Astrophysics Data System (ADS)

    Chizhevskaya, S. V.; Stefanovsky, S. V.

    2000-07-01

    The problem of excess weapons plutonium disposition is suggested to be solved by means of its incorporation in stable ceramics with high chemical durability and radiation resistivity. The most promising host phases for plutonium as well as uranium and neutron poisons (gadolinium, hafnium) are zirconolite, pyrochlore, zircon, zirconia [1,2], and murataite [3]. Their production requires high temperatures and a fine-grained homogeneous precursor to reach final waste form with high quality and low leachability. Currently various routes to homogeneous products preparation such as sol-gel technology, wet-milling, and grinding in a ball or planetary mill are used. The best result demonstrates sol-gel technology but this route is very complicated. An alternative technology for preparation of ceramic precursors is the treatment of the oxide batch with high mechanical energy [4]. Such a treatment produces combination of mechanical (fine milling with formation of various defects, homogenization) and chemical (split bonds with formation of active centers—free radicals, ion-radicals, etc.) effects resulting in higher reactivity of the activated batch.

  3. Deposition of copper from Cu(i) and Cu(ii) precursors onto HOPG surface: Role of surface defects and choice of a precursor

    NASA Astrophysics Data System (ADS)

    Duan, Yichen; Teplyakov, Andrew V.

    2017-02-01

    The surface reactivity of two copper-containing precursors, (Cu(hfac)2 and Cu(hfac)VTMS, where hfac is hexafluoroacetyloacetonate and VTMS is vinyltrimethylsilane), was investigated by dosing the precursors onto a surface of highly ordered pyrolytic graphite (HOPG) at room temperature. The behavior of these precursors on a pristine HOPG was compared to that on a surface activated by ion sputtering and subsequent oxidation to induce controlled surface defects. X-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy were used to confirm copper deposition and its surface distribution, and to compare with the results of scanning electron microscopy and atomic force microscopy investigations. As expected, surface defects promote copper deposition; however, the specific structures deposited depend on the deposition precursor. Density functional theory was used to mimic the reactions of each precursor molecule on this surface and to determine the origins of this different reactivity.

  4. Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors formed by such methods

    DOEpatents

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.

    2014-09-09

    Methods of forming single source precursors (SSPs) include forming intermediate products having the empirical formula 1/2{L.sub.2N(.mu.-X).sub.2M'X.sub.2}.sub.2, and reacting MER with the intermediate products to form SSPs of the formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2, wherein L is a Lewis base, M is a Group IA atom, N is a Group IB atom, M' is a Group IIIB atom, each E is a Group VIB atom, each X is a Group VIIA atom or a nitrate group, and each R group is an alkyl, aryl, vinyl, (per)fluoro alkyl, (per)fluoro aryl, silane, or carbamato group. Methods of forming polymeric or copolymeric SSPs include reacting at least one of HE.sup.1R.sup.1E.sup.1H and MER with one or more substances having the empirical formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2 or L.sub.2N(.mu.-X).sub.2M'(X).sub.2 to form a polymeric or copolymeric SSP. New SSPs and intermediate products are formed by such methods.

  5. Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors and intermediate products formed by such methods

    DOEpatents

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.

    2012-12-04

    Methods of forming single source precursors (SSPs) include forming intermediate products having the empirical formula 1/2{L.sub.2N(.mu.-X).sub.2M'X.sub.2}.sub.2, and reacting MER with the intermediate products to form SSPs of the formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2, wherein L is a Lewis base, M is a Group IA atom, N is a Group IB atom, M' is a Group IIIB atom, each E is a Group VIB atom, each X is a Group VIIA atom or a nitrate group, and each R group is an alkyl, aryl, vinyl, (per)fluoro alkyl, (per)fluoro aryl, silane, or carbamato group. Methods of forming polymeric or copolymeric SSPs include reacting at least one of HE.sup.1R.sup.1E.sup.1H and MER with one or more substances having the empirical formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2 or L.sub.2N(.mu.-X).sub.2M'(X).sub.2 to form a polymeric or copolymeric SSP. New SSPs and intermediate products are formed by such methods.

  6. Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors formed by such methods

    DOEpatents

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.

    2016-04-19

    Methods of forming single source precursors (SSPs) include forming intermediate products having the empirical formula 1/2{L.sub.2N(.mu.-X).sub.2M'X.sub.2}.sub.2, and reacting MER with the intermediate products to form SSPs of the formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2, wherein L is a Lewis base, M is a Group IA atom, N is a Group IB atom, M' is a Group IIIB atom, each E is a Group VIB atom, each X is a Group VIIA atom or a nitrate group, and each R group is an alkyl, aryl, vinyl, (per)fluoro alkyl, (per)fluoro aryl, silane, or carbamato group. Methods of forming polymeric or copolymeric SSPs include reacting at least one of HE.sup.1R.sup.1E.sup.1H and MER with one or more substances having the empirical formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2 or L.sub.2N(.mu.-X).sub.2M'(X).sub.2 to form a polymeric or copolymeric SSP. New SSPs and intermediate products are formed by such methods.

  7. MetNet Precursor - Network Mission to Mars

    NASA Astrophysics Data System (ADS)

    Harri, Arri-Matti

    2010-05-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The first MetNet vehicle, MetNet Precursor, slated for launch in 2011. The MetNet development work started already in 2001. The actual practical Precursor Mission development work started in January 2009 with participation from various space research institutes and agencies. The scientific rationale and goals as well as key mission solutions will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Time-resolved in situ Martian meteorological measurements acquired by the Viking, Mars Pathfinder and Phoenix landers and remote sensing observations by the Mariner 9, Viking, Mars Global Surveyor, Mars Odyssey and the Mars Express orbiters have provided the basis for our current understanding of the behavior of weather and climate on Mars. However, the available amount of data is still scarce and a wealth of additional in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes to address microscale and mesoscale atmospheric phenomena. Detailed characterization of the Martian atmospheric circulation patterns and climatological cycles requires simultaneous in situ atmospheric observations. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe

  8. Instellar Exploration: Propulsion Options for Precursors and Beyond

    NASA Technical Reports Server (NTRS)

    Johnson, Charles Les; Leifer, Stephanie

    1999-01-01

    NASA is considering a mission to explore near-interstellar space early in the next decade as the first step toward a vigorous interstellar exploration program. A key enabling technology for such an ambitious science and exploration effort is the development of propulsion systems capable of providing fast trip times; mission duration should not exceed the professional lifetime of the investigative team. Advanced propulsion technologies that might support an interstellar precursor mission early in the next century include some combination of solar sails, nuclear electric propulsion systems, and aerogravity assists. Follow-on missions to far beyond the heliopause will require the development of propulsion technologies that are only at the conceptual stage today. These include 1) matter-antimatter annihilation, 2) beamed-energy sails, and 3) fusion systems. For years, the scientific community has been interested in the development of solar sail technology to support exploration of the inner and outer planets. Progress in thin-film technology and the development of technologies that may enable the remote assembly of large sails in space are only now maturing to the point where ambitious interstellar precursor missions can be considered. Electric propulsion is now being demonstrated for planetary exploration by the Deep Space 1 mission. The primary issues for it's adaptation to interstellar precursor applications include the nuclear reactor that would be required and the engine lifetime. For further term interstellar missions, matter-antimatter annihilation propulsion system concepts have the highest energy density of any propulsion systems using onboard propellants. However, there are numerous challenges to production and storage of antimatter that must be overcome before it can be seriously considered for interstellar flight. Off-board energy systems (laser sails) are candidates for long-distance interstellar flight but development of component technologies and

  9. Activated microporous materials through polymerization of microemulsion precursors

    NASA Astrophysics Data System (ADS)

    Venkatesan, Arunkumar

    Microemulsions have been well studied for their unique characteristics. They are isotropic, thermodynamically stable and microstructured mixtures of oil and water stabilized by one or more surfactant species. They are formed spontaneously and are thermodynamically stable. Microemulsion precursors can be polymerized to make microporous solids with controlled pore structure and sizes. These polymeric solids have been studied extensively in the past. Although the fundamental properties of the microporous solids have been studied in depth, the development of specific applications that will utilize the unique properties of these solids has not been exhaustively researched. The current work establishes the feasibility of making activated microporous solids from microemulsion precursors, by the use of a ligand that chelates metals and also attaches itself to the polymer monolith. It also uses a novel 'in-situ' incorporation by combining the formulation and incorporation steps into one. The research objectives are, to formulate a microemulsion system that can yield useful microporous solids upon polymerization and activation, to characterize these solids using existing techniques available for analysis of similar microporous solids, to identify and understand the effect of the variables in the system and to study the influence of these variables on the performance characteristics of this material. Characterization techniques like Differential Scanning Calorimetry, Thermogravimetric Analysis and Scanning Electron Microscopy were used. A hydroxyethylmethylmethacrylate/methylmethacrylate/aqueous phase containing 10% SDS' system was chosen as the precursor microemulsion and the corresponding microporous solids were made. A metal chelating ligand, Congo Red, was incorporated onto the microporous polymer using NaOH as a binding agent. The ability of the resultant 'activated' microporous solid to remove metal ions from solution, was evaluated. The metal ion chosen was chromium

  10. Aluminum borate nanowires from the pyrolysis of polyaminoborane precursors.

    PubMed

    Du, Van An; Jurca, Titel; Whittell, George R; Manners, Ian

    2016-01-21

    Polyaminoboranes [N(R)H-BH2]n (1: R = H, 2: R = Me) were pyrolyzed on a range of substrates: silicon, metal foils (stainless steel, nickel, and rhodium), and sapphire wafers, as well as on Al2O3 and AlN powders. The pyrolysis of 2 on a Si-wafer resulted in porous nanostructures containing hexagonal-boron nitride (h-BN). In the case of 1 or H3N·BH3 as precursor, using rhodium foil as substrate afforded amorphous B and N-containing nanostructures, and polydisperse spherical nanoparticles, respectively. Switching the substrate to sapphire wafers, as well as to Al2O3 or AlN powders, resulted in formation of crystalline Al5BO9 nanostructures (nanowires, nanotubes, and nanoribbons). For sapphire wafers, the size of the resulting nanowires was influenced by modifying the surface defect density.

  11. MicroRNA precursors are not structurally robust but plastic.

    PubMed

    Rodrigo, Guillermo; Elena, Santiago F

    2013-01-01

    Robustness is considered a ubiquitous property of living systems at all levels of organization, and small noncoding RNA (sncRNA) is a genuine model for its study at the molecular level. In this communication, we question whether microRNA precursors (pre-miRNAs) are actually structurally robust, as previously suggested. We found that natural pre-miRNAs are not more robust than expected under an appropriate null model. On the contrary, we found that eukaryotic pre-miRNAs show a significant enrichment in conformational flexibility at the thermal equilibrium of the molecule, that is, in their plasticity. Our results further support the selection for functional diversification and evolvability in sncRNAs.

  12. Precursors for chemical and photochemical vapor deposition of copper metal

    NASA Astrophysics Data System (ADS)

    James, Alicia Marie

    The colorless square-planar cluster [CuN(SiMe3)2] 4, which contains four Cu(I) ions with four bridging amide groups, was studied as a precursor for chemical and photochemical vapor deposition of Cu metal. The cluster phosphoresces in CH2Cl2 solution and in the solid state at room temperature. Its electronic spectrum in CH 2Cl2 consists of two intense bands which are assigned to symmetry-allowed 3d → 4p transitions; the phosphorescence is also likely to be metal-centered. Solid [CuN(SiMe3)2]4 luminesces with approximately the same spectrum as that of the CH2Cl2 solutions. At 77 K, the solid-state luminescence red-shifts slightly. The emission lifetime in glassy Et2O solution is 690 mus. [CuN(SiMe3) 2]4 deposits Cu metal via chemical vapor deposition under H2 carrier gas at substrate temperatures of 145--200°C. Deposition also occurs photochemically beginning at 136--138°C under near-UV irradiation. The preparation of monomeric derivatives of [CuN(SiMe3) 2]4 was attempted by using neutral donor ligands L (e.g. LnCuN(SiMe3)2; L = CO, PR3, CN-t-Bu; n = 1--3). The target compounds were expected to be more volatile than the copper cluster and still maintain photosensitivity. CuCl and [Cu(CH 3CN)4]PF6 were used as starting materials. Even in the presence of L, [CuN(SiMe3)2] 4 is a major product in reactions using CuCl and NaN(SiCH3) 2- [Cu(CH3CN)4]PF6 was a promising route for the monomeric Cu(I) complexes because of ready dissociation of its acetonitrile ligands. However, the characterization of these complexes was unsuccessful. Other Cu(I) amide clusters have been prepared; they may also be suitable for chemical and photochemical vapor deposition of Cu. [CuNEt2] 4, [CuN(i-Pr)2]4, and [CuN(t-Bu)(SiMe 3)]4 are phosphorescent though they are very air sensitive. They should be more volatile and produce Cu metal films more readily than [CuN(SiMe3)2]4 Cu(hfac)2 is a versatile Lewis acid, forming adducts with a variety of bases. The bases that were used were ethylene

  13. Finite Element Analysis of Extrusion of Multifilamentary Superconductor Precursor

    SciTech Connect

    Peng, X.; Sumption, M.D.; Collings, E.W.

    2004-06-28

    The extrusion of multifilamentary superconductor precursor billets has been modeled using finite element analysis. The billet configuration was 6 around 1, with the subelement consisting of Nb rods, and the outer can or sleeve was Cu. Two general cases were investigated, those in which the re-stack rods were initially; (i) round, and (ii) hexed. A thermo-mechanical, elasto-plastic, finite-element method was used to analyze the extrusion process. In this 3D FEM model, the initial state of the billet was assumed to be absent of bonding. A typical die angle (2{alpha}=45 deg.) and a series of extrusion ratios were selected to perform the simulation and the corresponding stress and strain distributions of the two billet variants processed were compared. Based on the stress and deformation created at the rod/rod and rod/sleeve interfaces, the bonding conditions generated through the extrusion were investigated.

  14. An Indian Ocean precursor for Indian summer monsoon rainfall variability

    NASA Astrophysics Data System (ADS)

    Sreejith, O. P.; Panickal, S.; Pai, S.; Rajeevan, M.

    2015-11-01

    The Indian summer monsoon rainfall (ISMR) depicts large interannual variability strongly linked with El Niño-Southern Oscillation (ENSO). However, many of the El Niño years were not accompanied by deficient ISMR. The results from the study reveal the significant role of coupled air-sea interaction over the tropical Indian Ocean (IO) in modifying the ENSO-ISMR association. The IO warm water volume (WWV), a measure of heat content variations in the equatorial IO has strong influence on ISMR. A deepening (shoaling) of thermocline in the eastern equatorial IO (EEIO) during late boreal spring (April-May) accompanied by increase (decrease) in WWV anomalies weaken (enhance) the ISMR by enhancing (suppressing) the convection over EEIO resulting in the below (above) normal ISMR. Thus, the changes in the WWV anomalies in the EEIO along with ENSO conditions during boreal spring can be considered as a precursor for the performance of subsequent ISMR.

  15. Resonant infrared pulsed laser deposition of a polyimide precursor

    NASA Astrophysics Data System (ADS)

    Dygert, N. L.; Schriver, K. E.; Haglund, R. F., Jr.

    2007-04-01

    Poly(amic acid) (PAA), a precursor to polyimide, was successfully deposited on substrates without reaching curing temperature, by resonant infrared pulsed laser ablation. The PAA was prepared by dissolving pyromellitic dianhydride and 4, 4' oxidianiline in the polar solvent Nmethyl pyrrolidinone (NMP). The PAA was deposited in droplet-like morphologies when ablation occurred in air, and in string-like moieties in the case of ablation in vacuum. In the as-deposited condition, the PAA was easily removed by washing with NMP; however, once cured thermally for thirty minutes, the PAA hardened, indicating the expected thermosetting property. Plume shadowgraphy showed very clear contrasts in the ablation mechanism between ablation of the solvent alone and the ablation of the PAA, even at low concentrations. A Wavelength dependence in plume velocity was also observed.

  16. Current Development in Isoprenoid Precursor Biosynthesis and Regulation

    PubMed Central

    Chang, Wei-chen; Song, Heng; Liu, Hung-wen; Liu, Pinghua

    2013-01-01

    Isoprenoids are one of the largest classes of natural products and all of them are constructed from two precursors, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). For decades, the mevalonic acid (MVA) pathway was proposed to be the only IPP and DMAPP biosynthetic pathway. This review summarizes the newly discovered IPP and DMAPP production pathways since late 1990s, their distribution among different kingdoms, and their roles in secondary metabolite production. These new IPP and DMAPP production pathways include the methylerythritol phosphate (MEP) pathway, a modified MVA pathway, and the 5-Methylthioadenosine shunt pathway. Relative to the studies on the MVA pathway, information on the MEP pathway regulation is limited and the mechanistic details of several of its novel transformations remain to be addressed. Current status on both MEP pathway regulation and mechanistic issues are also presented. PMID:23891475

  17. Early precursors and enabling skills of reading acquisition.

    PubMed

    Lundberg, Ingvar

    2009-12-01

    Research on early linguistic precursors and enabling skills of reading acquisition among young children is reviewed. Language development starts early in infancy when the child learns to categorize the speech sounds according to the pattern typical of the mother tongue. Equipped with these sound categories the child is ready to learn to segment words from the sound stream and to understand and to use words. The precise phonological representation of words will facilitate the important development of phonological awareness, a basic prerequisite for reading acquisition. This paper reviews some of my longitudinal research and training studies indicating the causal direction of the relation between phonological awareness and reading and includes some ongoing studies, where gender differences, socio-economic factors, dose-response-effects and motivational factors are explored. Preventive and remedial implications of the findings are pointed out. Finally, the complexity of the causal relationships between different aspects of early language development, including genetic influences and later reading is pointed out.

  18. Tilt precursors before earthquakes on the San Andreas fault, California

    USGS Publications Warehouse

    Johnston, M.J.S.; Mortensen, C.E.

    1974-01-01

    An array of 14 biaxial shallow-borehole tiltmeters (at 10-7 radian sensitivity) has been installed along 85 kilometers of the San Andreas fault during the past year. Earthquake-related changes in tilt have been simultaneously observed on up to four independent instruments. At earthquake distances greater than 10 earthquake source dimensions, there are few clear indications of tilt change. For the four instruments with the longest records (>10 months), 26 earthquakes have occurred since July 1973 with at least one instrument closer than 10 source dimensions and 8 earthquakes with more than one instrument within that distance. Precursors in tilt direction have been observed before more than 10 earthquakes or groups of earthquakes, and no similar effect has yet been seen without the occurrence of an earthquake.

  19. Oxidation and formation of deposit precursors in hydrocarbon fuels

    NASA Technical Reports Server (NTRS)

    Buttrill, S. E., Jr.; Mayo, F. R.; Lan, B.; St.john, G. A.; Dulin, D.

    1982-01-01

    A practical fuel, home heating oil no. 2 (Fuel C), and the pure hydrocarbon, n-dodecane, were subjected to mild oxidation at 130 C and the resulting oxygenated reaction products, deposit precursors, were analyzed using field ionization mass spectrometry. Results for fuel C indicated that, as oxidation was initially extended, certain oxygenated reaction products of increasing molecular weights in the form of monomers, dimers and some trimers were produced. Further oxidation time increase resulted in further increase in monomers but a marked decrease in dimers and trimers. This suggests that these larger molecular weight products have proceeded to form deposit and separated from the fuel mixture. Results for a dodecane indicated that yields for dimers and trimers were very low. Dimers were produced as a result of interaction between oxygenated products with each other rather than with another fuel molecule. This occurred even though fuel molecule concentration was 50 times, or more greater than that for these oxygenated reaction products.

  20. Damage precursor measurements on UV-optical coatings

    SciTech Connect

    Ettrich, K.; Blaschke, H.; Welsch, E.

    1995-12-31

    For application in UV thin film optics the thermal contribution to the laser-induced optical breakdown was investigated utilizing time-resolved photothermal probe beam deflection (MIRAGE) technique. The potentiality of this method for the determination of both the subdamage range and the onset of single-shot-damage of Al{sub 2}O{sub 3}/SiO{sub 2} and LaF{sub 3}/MgF{sub 2} high-reflective coatings by using the thermal branch of the MIRAGE technique could be demonstrated. Examining the dielectric mirrors by 248 nm KrF laser irradiation, distinct damage precursor features were found. Thus, the physical origin of the UV pulsed radiation breakdown in HR coatings can be elucidated.

  1. Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles

    PubMed Central

    Riedel, Dietmar; Hua, Yunfeng; Hüve, Jana; Wilhelm, Benjamin G.; Klingauf, Jürgen

    2011-01-01

    A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling. PMID:21556148

  2. Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors

    PubMed Central

    Canli, Özge; Alankuş, Yasemin B.; Grootjans, Sasker; Vegi, Naidu; Hültner, Lothar; Hoppe, Philipp S.; Schroeder, Timm; Vandenabeele, Peter; Bornkamm, Georg W.

    2016-01-01

    Maintaining cellular redox balance is vital for cell survival and tissue homoeostasis because imbalanced production of reactive oxygen species (ROS) may lead to oxidative stress and cell death. The antioxidant enzyme glutathione peroxidase 4 (Gpx4) is a key regulator of oxidative stress–induced cell death. We show that mice with deletion of Gpx4 in hematopoietic cells develop anemia and that Gpx4 is essential for preventing receptor-interacting protein 3 (RIP3)-dependent necroptosis in erythroid precursor cells. Absence of Gpx4 leads to functional inactivation of caspase 8 by glutathionylation, resulting in necroptosis, which occurs independently of tumor necrosis factor α activation. Although genetic ablation of Rip3 normalizes reticulocyte maturation and prevents anemia, ROS accumulation and lipid peroxidation in Gpx4-deficient cells remain high. Our results demonstrate that ROS and lipid hydroperoxides function as not-yet-recognized unconventional upstream signaling activators of RIP3-dependent necroptosis. PMID:26463424

  3. Electrochemical behavior of carbon aerogels derived from different precursors

    SciTech Connect

    Pekala, R.W.; Alviso, C.T.; Nielsen, J.K.; Tran, T.D.; Reynolds, G.A.M.; Dresselhaus, M.S.

    1995-12-31

    The ability to tailor the structure and properties of porous carbons has led to their increased use as electrodes in energy storage devices. The research focuses on the synthesis and characterization of carbon aerogels for use in electrochemical double layer capacitors.Carbon aerogels are formed from the sol-gel polymerization of (1) resorcinol-formaldehyde or (2) phenolic-furfural, followed by supercritical drying from carbon dioxide, and subsequent pyrolysis in an inert atmosphere. These materials can be produced as monoliths, composites, thin films, powders, or microspheres. In all cases, the aerogels have an open-cell structure with an ultrafine pore size (< 100 nm), high surface area (400--1,100 m{sup 2}/g), and a solid matrix composed of interconnected particles, fibers, or platelets with characteristic dimensions of 10 nm. This paper examines the effects of the carbon precursor and processing conditions on electrochemical performance in aqueous and organic electrolytes.

  4. Oligodendrocyte precursors migrate along vasculature in the developing nervous system.

    PubMed

    Tsai, Hui-Hsin; Niu, Jianqin; Munji, Roeben; Davalos, Dimitrios; Chang, Junlei; Zhang, Haijing; Tien, An-Chi; Kuo, Calvin J; Chan, Jonah R; Daneman, Richard; Fancy, Stephen P J

    2016-01-22

    Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation.

  5. A primitive cell origin for B-cell precursor ALL?

    PubMed

    Cox, C V; Blair, A

    2005-01-01

    A stem cell origin has been described for both acute and chronic myelogenous leukemias. In contrast, childhood B-cell precursor acute lymphoblastic leukemia (ALL) is thought to arise in committed B-lineage cells. Recently described in vitro and in vivo model systems that support the proliferation and expansion of ALL cells have provided new tools to investigate the cellular targets for the origin of this malignancy. Evidence suggests that some subtypes of childhood ALL have a primitive cell origin and share many immunophenotypic characteristics with normal progenitor cells. These leukemic stem cells may be resistant to current therapeutic strategies designed to kill the bulk ALL cell population and subsequent relapses may arise from this population. More precise definition of these ALL stem cells through combined analyses of antigen expression, genetic lesions, and functionality is essential for the development of more effective, targeted therapeutic strategies.

  6. Superhydrophobic Ceramic Coatings by Solution Precursor Plasma Spray

    PubMed Central

    Cai, Yuxuan; Coyle, Thomas W.; Azimi, Gisele; Mostaghimi, Javad

    2016-01-01

    This work presents a novel coating technique to manufacture ceramic superhydrophobic coatings rapidly and economically. A rare earth oxide (REO) was selected as the coating material due to its hydrophobic nature, chemical inertness, high temperature stability, and good mechanical properties, and deposited on stainless steel substrates by solution precursor plasma spray (SPPS). The effects of various spraying conditions including standoff distance, torch power, number of torch passes, types of solvent and plasma velocity were investigated. The as-sprayed coating demonstrated a hierarchically structured surface topography, which closely resembles superhydrophobic surfaces found in nature. The water contact angle on the SPPS superhydrophobic coating was up to 65% higher than on smooth REO surfaces. PMID:27091306

  7. NASAs Evolvable Mars Campaign: Mars Moons Robotic Precursor

    NASA Technical Reports Server (NTRS)

    Gernhardt, Michael L.; Abercromby, Andrew F. J.; Abell, Paul A.; Love, Stanley G.; Lee, David E.; Chappell, Steven P.; Howe, A. Scott; Friedensen, Victoria

    2015-01-01

    Human exploration missions to the moons of Mars are being considered within NASA's Evolvable Mars Campaign (EMC) as an intermediate step for eventual human exploration and pioneering of the surface of Mars. A range of mission architectures is being evaluated in which human crews would explore one or both moons for as little as 14 days or for as long as 500 days with a variety of orbital and surface habitation and mobility options being considered. Relatively little is known about the orbital, surface, or subsurface characteristics of either moon. This makes them interesting but challenging destinations for human exploration missions during which crewmembers must be able to effectively conduct scientific exploration without being exposed to undue risks due to radiation, dust, micrometeoroids, or other hazards. A robotic precursor mission to one or both moons will be required to provide data necessary for the design and operation of subsequent human systems and for the identification and prioritization of scientific exploration objectives. This paper identifies and discusses considerations for the design of such a precursor mission based on current human mission architectures. Objectives of a Mars' moon precursor in support of human missions are expected to include: 1) identifying hazards on the surface and the orbital environment at up to 50-km distant retrograde orbits; 2) collecting data on physical characteristics for planning of detailed human proximity and surface operations; 3) performing remote sensing and in situ science investigations to refine and focus future human scientific activities; and 4) prospecting for in situ resource utilization. These precursor objectives can be met through a combination or remote sensing (orbital) and in-situ (surface) measurements. Analysis of spacecraft downlink signals using radio science techniques would measure the moon's mass, mass distribution, and gravity field, which will be necessary to enable trajectory planning

  8. Characterization of precursors to trihalomethanes formation in Bangkok source water.

    PubMed

    Panyapinyopol, Bunyarit; Marhaba, Taha F; Kanokkantapong, Vorapot; Pavasant, Prasert

    2005-04-11

    Resin adsorption techniques using three types of resin (DAX-8, AG-MP-50, and WA-10) were employed to characterize the raw water (RW) from the major 3 million m3/day (793 million gal/day) drinking water treatment plant in Bangkok, Thailand. The dissolved organic carbon (DOC) mass distribution sequences of the six organic fractions in raw water, from high to low, were hydrophilic neutral (HPIN), hydrophobic acid (HPOA), hydrophilic acid (HPIA), hydrophobic neutral (HPON), hydrophilic base (HPIB), and hydrophobic base (HPOB). HPIN and HPOA were the two main precursors for trihalomethanes formation (THMFP) in this water source following chlorination. The chlorination of HPON and HPIN fractions only led to the formation of mostly chloroform, while other organic fractions formed both chloroform and bromodichloromethane. The linear dependency between each organic fraction concentration and THMFP indicated that the reactions of each organic fraction with chlorine were first-order.

  9. Single Source Precursors for Thin Film Solar Cells

    NASA Technical Reports Server (NTRS)

    Banger, Kulbinder K.; Hollingsworth, Jennifer A.; Harris, Jerry D.; Cowen, Jonathan; Buhro, William E.; Hepp, Aloysius F.

    2002-01-01

    The development of thin film solar cells on flexible, lightweight, space-qualified substrates provides an attractive cost solution to fabricating solar arrays with high specific power, (W/kg). The use of a polycrystalline chalcopyrite absorber layer for thin film solar cells is considered as the next generation photovoltaic devices. At NASA GRC we have focused on the development of new single source precursors (SSP) and their utility to deposit the chalcopyrite semi-conducting layer (CIS) onto flexible substrates for solar cell fabrication. The syntheses and thermal modulation of SSPs via molecular engineering is described. Thin-film fabrication studies demonstrate the SSPs can be used in a spray CVD (chemical vapor deposition) process, for depositing CIS at reduced temperatures, which display good electrical properties, suitable for PV (photovoltaic) devices.

  10. Electrochemical behavior of carbon aerogels derived from different precursors

    SciTech Connect

    Pekala, R.W.; Alviso, C.T.; Nielson, J.K.; Tran, T.D.; Reynolds, G.M.; Dresshaus, M.S.

    1995-04-01

    The ability to tailor the structure and properties of porous carbons has led to their increased use as electrodes in energy storage devices. Our research focuses on the synthesis and characterization of carbon aerogels for use in electrochemical double layer capacitors. Carbon aerogels are formed from the sol-gel polymerization of (1) resorcinol-formaldehyde or (2) phenolic-furfural, followed by supercritical drying from carbon dioxide, and subsequent pyrolysis in an inert atmosphere. These materials can be produced as monoliths, composites, thin films, powders, or microspheres. In all cases, the areogels have an open-cell structure with an ultrafine pore size (<100 nm), high surface area (400-1 100 m{sup 2}/g), and a solid matrix composed of interconnected particles, fibers, or platelets with characteristic dimensions of 10 nm. This paper examines the effects of the carbon precursor and processing conditions on electrochemical performance in aqueous and organic electrolytes.

  11. Catalytic growth of boron nitride nanotubes using gas precursors

    NASA Astrophysics Data System (ADS)

    Guo, L.; Singh, R. N.

    2009-01-01

    Hexagonal boron nitride nanotubes (BNNTs) are synthesized at low substrate temperatures on nickel (Ni)- or cobalt (Co)-coated oxidized Si (1 1 1) wafers in a microwave plasma-enhanced chemical vapor deposition (MPCVD) system by decomposition and reaction of gas mixtures consisting of B 2H 6-NH 3-H 2. The growth of one-dimensional (1-D) BN nanostructures is obtained at an optimum combination of catalyst film thickness, substrate temperature, and precursor gas flow rates. The morphology, composition and structural properties of the BNNTs are analyzed by scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDX), selected area diffraction (SAD), and Raman spectroscopy. The patterned growth of BNNTs is also demonstrated.

  12. Betaine suppressed Aβ generation by altering amyloid precursor protein processing.

    PubMed

    Liu, Xiu-Ping; Qian, Xiang; Xie, Yue; Qi, Yan; Peng, Min-Feng; Zhan, Bi-Cui; Lou, Zheng-Qing

    2014-07-01

    Betaine was an endogenous catabolite of choline, which could be isolated from vegetables and marine products. Betaine could promote the metabolism of homocysteine in healthy subjects and was used for hyperlipidemia, coronary atherosclerosis, and fatty liver in clinic. Recent findings shown that Betaine rescued neuronal damage due to homocysteine induced Alzheimer's disease (AD) like pathological cascade, including tau hyperphosphorylation and amyloid-β (Aβ) deposition. Aβ was derived from amyloid precursor protein (APP) processing, and was a triggering factor for AD pathological onset. Here, we demonstrated that Betaine reduced Aβ levels by altering APP processing in N2a cells stably expressing Swedish mutant of APP. Betaine increased α-secretase activity, but decreased β-secretase activity. Our data indicate that Betaine might play a protective role in Aβ production.

  13. Selecting membranes for removing NOM and DBP precursors

    SciTech Connect

    Fu, P.; Ruiz, H. ); Thompson, K.; Spangenberg, C. )

    1994-12-01

    A membrane filtration pilot plant was operated for one year to evaluate the removal of natural organic matter and disinfection by-product precursors from a highly colored groundwater in Orange County, California. Two nanofiltration (NF) membranes--a traditional softening membrane and a high-permeability, charged membrane--were selected for pilot-scale testing based on bench-scale tests of eight NF and ultrafiltration membranes. The high-permeability NF membrane demonstrated superior organics removal at very high recovery and flux. It also allowed most inorganic constituents to pass through. The concentrate of low total dissolved solids reduced inorganic fouling and made concentrate reuse possible. The article also presents preliminary design criteria and a cost opinion for full-scale treatment facilities.

  14. The Fe/Mn constraint on precursors of basaltic achondrites

    NASA Technical Reports Server (NTRS)

    Delaney, Jeremy S.; Boesenberg, Joseph S.

    1993-01-01

    Most achondritic meteorites have Fe/Mn ratios that are lower than those of carbonaceous chondrites and of course are lower than the solar system abundance ratio of these elements. Models of the origin of achondritic assemblages must, therefore, account for these ratios. Fe/Mn ratios are suggested to be distinctive for samples from each achondrite parent body and for the Earth and Moon, but the correspondence between the Fe/Mn systematics of achondrites and chondritic precursors is unclear. Most models of achondrite genesis involve magmatic differentiation of chondritic precursors. The Fe/Mn difference between achondrites and chondrites is particularly significant since Fe and Mn are geochemically similar elements with similar partitioning behavior in familiar magmatic systems and are generally coupled during crystal-liquid fractionation. In contrast, however, Mn is more volatile than Fe in a nebular setting. Variation of Fe/Mn ratios based on the relative volatility of these elements in the early nebula provides a constraint for models by which the basaltic achondrites (with Fe/Mn ratios approximately = 25-50) are derived from mixtures of nebular components that were enriched in volatile components such as Mn. However, such volatile enriched components have not been identified in chondrites. When the abundance in achondrites of elements of similar volatility is examined, anomalies appear. For example, Na is massively depleted in basaltic achondrites when compared to Mn. These anomalies might be explained using current models but the alternative hypothesis, that Fe/Mn ratio is controlled not by nebular volatility constraints, but by planetary differentiation should be explored.

  15. Precursors of ENSO Events from 27 Years of Satellite Data

    NASA Astrophysics Data System (ADS)

    Capotondi, A.; Ricciardulli, L.

    2015-12-01

    The present study examines the role of different mechanisms as precursors for ENSO diversity by analyzing high-quality satellite observations of several key variables for the past 27 years, complemented by subsurface information from ocean reanalysis (GODAS, SODAsi). Our objective is to clarify the relative importance of large-scale atmospheric forcing from the Northern and Southern Hemispheres, as well as tropical atmospheric noise and ocean background conditions in triggering different ENSO types, thus providing insights in the event predictability and possible lead times. This investigation uses an extensive suite of ocean satellite retrievals from microwave sensors, radiometers and scatterometers, all intercalibrated and consistently processed at Remote Sensing Systems. The satellite data record of wind speed, columnar water vapor, cloud water, and precipitation begins in 1988 with the first SSMI. Through-clouds SST observations started in 1998 with TMI. Wind vectors observations started with the scatterometer QuikSCAT in 1999. All of these variables have now been continuously monitored and processed to a high accuracy level, suitable for climate studies, and are available at high frequency, twice daily for each instrument, and at a fine spatial resolution of 0.25 degrees. We first examine the large-scale extra-tropical precursors in both the Northern and Southern Hemispheres and their relative influence in triggering each El Niño/La Niña event during the satellite era. We then consider the role played by atmospheric noise in the form of Westerly Wind Bursts (WWBs) in triggering different event types, and the possible interplay of the WWB activity and extra-tropical influences. In particular, the relationship of the WWB amplitude and longitudinal evolution with the location of the eastern edge of the Warm Pool is examined over the total length of the satellite record. Special attention is devoted to the evolution of equatorial Pacific conditions during 2014

  16. Human Myocardial Pericytes: Multipotent Mesodermal Precursors Exhibiting Cardiac Specificity

    PubMed Central

    Chen, William C.W.; Baily, James E.; Corselli, Mirko; Diaz, Mary; Sun, Bin; Xiang, Guosheng; Gray, Gillian A.; Huard, Johnny; Péault, Bruno

    2015-01-01

    Perivascular mesenchymal precursor cells (i.e. pericytes) reside in skeletal muscle where they contribute to myofiber regeneration; however, the existence of similar microvessel-associated regenerative precursor cells in cardiac muscle has not yet been documented. We tested whether microvascular pericytes within human myocardium exhibit phenotypes and multipotency similar to their anatomically and developmentally distinct counterparts. Fetal and adult human heart pericytes (hHPs) express canonical pericyte markers in situ, including CD146, NG2, PDGFRβ, PDGFRα, αSMA, and SM-MHC, but not CD117, CD133 and desmin, nor endothelial cell (EC) markers. hHPs were prospectively purified to homogeneity from ventricular myocardium by flow cytometry, based on a combination of positive- (CD146) and negative-selection (CD34, CD45, CD56, and CD117) cell lineage markers. Purified hHPs expanded in vitro were phenotypically similar to human skeletal muscle-derived pericytes (hSkMPs). hHPs express MSC markers in situ and exhibited osteo- chondro-, and adipogenic potentials but, importantly, no ability for skeletal myogenesis, diverging from pericytes of all other origins. hHPs supported network formation with/without ECs in Matrigel cultures; hHPs further stimulated angiogenic responses under hypoxia, markedly different from hSkMPs. The cardiomyogenic potential of hHPs was examined following 5-azacytidine treatment and neonatal cardiomyocyte co-culture in vitro, and intramyocardial transplantation in vivo. Results indicated cardiomyocytic differentiation in a small fraction of hHPs. In conclusion, human myocardial pericytes share certain phenotypic and developmental similarities with their skeletal muscle homologs, yet exhibit different antigenic, myogenic, and angiogenic properties. This is the first example of an anatomical restriction in the developmental potential of pericytes as native mesenchymal stem cells. PMID:25336400

  17. Structural comparison of nickel electrodes and precursor phases

    NASA Technical Reports Server (NTRS)

    Cornilsen, Bahne C.; Shan, Xiaoyin; Loyselle, Patricia

    1989-01-01

    A summary of previous Raman spectroscopic results and a discussion of important structural differences in the various phases of active mass and active mass precurors are presented. Raman spectra provide unique signatures for these phases, and allow one to distinguish each phase, even when the compound is amorphous to X-rays (i.e., does not scatter X-rays because of a lack of order and/or small particle size). The structural changes incurred during formation, charge and discharge, cobalt addition, and aging will be discussed and related to electrode properties. Important structural differences include NiO2 layer stacking, nonstoichiometry (especially cation-deficit nonstoichiometry), disorder, dopant content, and water content. The results indicate that optimal nickel active mass is non-close packed and nonstoichiometric. The formation process transforms precursor phases into this structure. Therefore, the precursor disorder, or lack thereof, influences this final active mass structure and the rate of formation. Aging processes induce structural change which is believed to be detrimental. The role of cobalt addition can be appreciated in terms of structures favored or stabilized by the dopant. In recent work, the in situ Raman technique to characterize the critical structural parameters was developed. An in situ method relates structure, electrochemistry, and preparation. In situ Raman spectra of cells during charge and discharge, either during cyclic voltammetry or under constant current conditions were collected. With the structure-preparation knowledge and the in situ Raman tool, it will be possible to define the structure-property-preparation relations in more detail. This instrumentation has application to a variety of electrode systems.

  18. First results on GlioLab/GlioSat Precursors Missions

    NASA Astrophysics Data System (ADS)

    Cappelletti, Chantal; Notarangelo, Angelo; Demoss, Darrin; Carella, Massimo

    2012-07-01

    Since 2009 GAUSS group is involved in a joint collaboration with Morehead State University (MSU) Space Science Center and IRCCS Casa Sollievo della Sofferenza (CSS) research labs with the aim to design a biomedical project in order to investigate if the combined effects of microgravity conditions and ionizing radiation increase or decrease the survival rate of cancer cells. The biological sample consists of Glioblastoma cancer cell line ANGM-CSS. Glioblastoma is a kind of cancer that can be treated after surgery only by radiotherapy using ionizing radiation. This treatment, anyway, results in a very low survival rate. This project uses different university space platforms: a CubeLab, named GlioLab, on board the International Space Station and the university microsatellite UniSat-5 designed by GAUSS. In addition a GlioLab/GlioSat precursor experiment has already flown two times with the Space Shuttle during the missions STS-134 and STS-135. The phase 0 or the precursor of GlioLab uses a COTS system, named Liquid Mixing Apparatus (LMA), to board the biological samples inside the Space Shuttle for thirty day . The LMA allows to board liquids inside a vial but is not equipped with environment control system. After landing the samples were investigated by researchers at CSS in Italy and at MSU in Kentucky. This paper deals with the experimental set up and the results obtained during the STS-134 and STS-135 missions and with the new evidences on the behavior of this kind of cancer. In particular the results obtained on the DNA analysis give a confirmation of the original idea of GLioLab/Gliosat project justifying the development of the two systems.

  19. In silico identification of novel hevein-like peptide precursors.

    PubMed

    Porto, William F; Souza, Valéria A; Nolasco, Diego O; Franco, Octávio L

    2012-11-01

    Lectins are proteins with ability to bind reversibly and non-enzymatically to a specific carbohydrate. They are involved in numerous biological processes and show enormous biotechnological potential. Among plant lectins, the hevein domain is extremely common, being observed in several kinds of lectins. Moreover, this domain is also observed in an important class of antimicrobial peptides named hevein-like peptides. Due to higher cysteine residues conservation, hevein-like peptides could be mined among the sequence databases. By using the pattern CX(4,5)CC[GS]X(2)GXCGX[GST]X(2,3)[FWY]C[GS]X[AGS] novel hevein-like peptide precursors were found from three different plants: Oryza sativa, Vitis vinifera and Selaginella moellendorffii. In addition, an hevein-like peptide precursor from the phytopathogenic fungus Phaeosphaeria nodorum was also identified. The molecular models indicate that they have the same scaffold as others, composed of an antiparallel β-sheet and short helices. Nonetheless, the fungal hevein-like peptide probably has a different disulfide bond pattern. Despite this difference, the complexes between peptide and N,N,N-triacetylglucosamine are stable, according to molecular dynamics simulations. This is the first report of an hevein-like peptide from an organism outside the plant kingdom. The exact role of an hevein-like peptide in the fungal biology must be clarified, while in plants they are clearly involved in plant defense. In summary, data here reported clear shows that an in silico strategy could lead to the identification of novel hevein-like peptides that could be used as biotechnological tools in the fields of health and agribusiness.

  20. The role of catalyst precursor anions in coal gasification

    SciTech Connect

    Abotsi, G.M.K.

    1992-08-28

    The aims of the proposed project are to enrich our understanding of the roles of various aqueous soluble catalyst precursor anions on the surface electrical properties of coal and to ascertain the influence of the surface charge on the adsorption, dispersion, and activities of calcium and potassium. These goals will be achieved by impregnating a North Dakota lignite (PSOC 1482) and its demineralized derivative with calcium or potassium catalyst precursors containing acetate (CH{sub 3}COO{sup {minus}}), chloride (Cl{sup {minus}}), nitrate (NO{sub 3}{sup {minus}}), sulfate (SO{sub 4}{sup 2{minus}}), and carbonate (CO{sub 3}{sup 2{minus}}) anions. Catalyst loading will be conducted under well-controlled conditions of solution pH and ionic strength. In the last quarter, the surface charge properties of the coal was determined as a function of acetate (CH{sub 3}COO{sup {minus}}), chloride (Cl{sup {minus}}), nitrate (NO{sup 3}{sup {minus}}), carbonate (CO{sub 3}{sup 2{minus}}) or sulfate (SO{sub 4}{sup 2{minus}})concentration using the respective potassium salts of these anions. In general, low anion concentrations (10{sup {minus}3} or 10{sup {minus}2} mol/L) had little effect on the zeta potentials of the coals. However, the surface charge densities of the coal become less negative at 10-1 mol/L of the nitrate, carbonate or sulfate anions. These trends suggest that the surface charge density of the coal is controlled by the adsorption of potassium ions (K{sup +}) onto the coal particles. The net negative charge on the coal panicles creates a repulsive force between the anions and the coal surface and prevents the anions from exerting any significant effect on the coal's electrokinetic properties.

  1. Interactions between oligodendrocyte precursors control the onset of CNS myelination

    PubMed Central

    Yang, Yan; Lewis, Rebecca; Miller, Robert H.

    2011-01-01

    The formation of CNS myelin is dependent on the differentiation of oligodendrocyte precursor cells (OPCs) and oligodendrocyte maturation. How the initiation of myelination is regulated is unclear but it is likely to depend on the development of competence by oligodendrocytes and receptivity by target axons. Here we identify an additional level of control of oligodendrocyte maturation mediated by interactions between the different cellular components of the oligodendrocyte lineage. During development oligodendrocyte precursors mature through a series of stages defined by labeling with monoclonal antibodies A2B5 and O4. Newly differentiated oligodendrocytes begin to express galactocerebroside recognized by O1 antibodies and subsequently mature to myelin basic protein (MBP) positive cells prior to formation of compact myelin. Using an in vitro brain slice culture system that supports robust myelination, the consequences of ablating cells at different stages of the oligodendrocyte lineage on myelination has been assayed. Elimination of all OPC lineage cells through A2B5+, O4+ and O1+ complement mediated cell lysis resulted in a delay in development of MBP cells and myelination. Selective elimination of early OPCs (A2B5+) also unexpectedly resulted in delayed MBP expression compared to controls suggesting early OPCs contribute to the timing of myelination onset. By contrast, elimination of differentiated (O1+) immature oligodendrocytes permanently inhibited the appearance of MBP+ cells suggesting that oligodendrocytes are critical to facilitate the maturation of OPCs. These data illuminate that the presence of intra-lineage feed-forward and feedback cues are important for timely myelination by oligodendrocytes. PMID:21144846

  2. Comparative examination of titania nanocrystals synthesized by peroxo titanic acid approach from different precursors.

    PubMed

    Liu, Yong-Jun; Aizawa, Mami; Wang, Zheng-Ming; Hatori, Hiroaki; Uekawa, Naofumi; Kanoh, Hirofumi

    2008-06-15

    Titanium dioxide nanocrystalline particles were synthesized by peroxo titanium acid (PTA) approach from titanium alkoxide and inorganic salt precursors, and their structural and surface properties, porosities, and photocatalytic activities were comparatively examined by XRD, TG/DTA, DRIFT, UV-vis, low temperature N(2) adsorption, and methyl orange (MO) degradation. It was found that nanoparticles with single anatase phase can be obtained from alkoxide precursor even near room temperature if synthesis conditions are appropriately controlled. PTA-derived anatase nanoparticles from titanium alkoxide precursor have smaller crystalline sizes and better porosities, and contain less amount of peroxo group and no organic impurities as compared to those from TiCl(4) precursor. The advantages in structural property, porosity, and surface properties (few deficiencies) lead to a much better photocatalytic activity for TiO(2) nanoparticles from titanium alkoxide precursor in comparison with those from TiCl(4) precursor.

  3. Single-source precursors for ternary chalcopyrite materials, and methods of making and using the same

    NASA Technical Reports Server (NTRS)

    Banger, Kulbinder K. (Inventor); Hepp, Aloysius F. (Inventor); Harris, Jerry D. (Inventor); Jin, Michael Hyun-Chul (Inventor); Castro, Stephanie L. (Inventor)

    2006-01-01

    A single source precursor for depositing ternary I-III-VI.sub.2 chalcopyrite materials useful as semiconductors. The single source precursor has the I-III-VI.sub.2 stoichiometry built into a single precursor molecular structure which degrades on heating or pyrolysis to yield the desired I-III-VI.sub.2 ternary chalcopyrite. The single source precursors effectively degrade to yield the ternary chalcopyrite at low temperature, e.g. below 500.degree. C., and are useful to deposit thin film ternary chalcopyrite layers via a spray CVD technique. The ternary single source precursors according to the invention can be used to provide nanocrystallite structures useful as quantum dots. A method of making the ternary single source precursors is also provided.

  4. Poly (acrylonitrile - co -1-vinylimidazole): A New Melt Processable Carbon Fiber Precursor

    DTIC Science & Technology

    2011-01-01

    REPORT Poly (acrylonitrile – co -1-vinylimidazole): A new melt processable carbon fiber precursor 14. ABSTRACT 16. SECURITY CLASSIFICATION OF...Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS Carbon fiber precursor, Thermal cross-linking, Melt processable Wesley P. Hoffman, Dennis W...Z39.18 - Poly (acrylonitrile – co -1-vinylimidazole): A new melt processable carbon fiber precursor Report Title ABSTRACT Acrylonitrile/1-vinylimidazole

  5. The control of N-nitrosodimethylamine, Halonitromethane, and Trihalomethane precursors by Nanofiltration.

    PubMed

    Ersan, Mahmut S; Ladner, David A; Karanfil, Tanju

    2016-11-15

    Nanofiltration (NF) is a promising technology for removing precursors of disinfection byproducts (DBPs) from source waters prior to oxidant addition in water treatment. The aims of this study were to investigate (i) the removal efficiencies of N-nitrosodimethylamine (NDMA), halonitromethane (HNM), and trihalomethane (THM) precursors by NF membranes from different source water types (i.e. surface water, wastewater impacted surface water, and municipal and industrial wastewater treatment effluents), (ii) the impact of membrane type, and (iii) the effects of background water components (i.e., pH, ionic strength, and Ca(2+)) on the removal of selected DBP precursors from different source waters. The results showed the overall precursor removal efficiencies were 57-83%, 48-87%, and 72-97% for NDMA, HNM, and THM precursors, respectively. The removal of NDMA precursors decreased with the increases in average molecular weight cut off and negative surface charge of NF membranes tested, while the removal of THM precursors was slightly affected. pH changes increased the removal of NDMA precursors, but pH did not affect the removal of THM and HNM precursors in municipal WWTP effluent. On the other hand, pH changes had little or no effect on DBP removal from industrial WWTP effluent. In addition, regardless of the membrane type or background water type/characteristics, ionic strength did not show any impact on DBP precursor removals. Lastly, an increase in Ca(2+) concentration enhanced the removal of NDMA precursors while a slight decrease and no effect was observed for THM and HNM precursors, respectively, in municipal WWTP effluent.

  6. Precursors of Halobenzoquinones and Their Removal During Drinking Water Treatment Processes.

    PubMed

    Wang, Wei; Qian, Yichao; Jmaiff, Lindsay K; Krasner, Stuart W; Hrudey, Steve E; Li, Xing-Fang

    2015-08-18

    Halobenzoquinones (HBQs) widely occur in drinking water treatment plant (DWTP) effluents; however, HBQ precursors and their removal by treatments remain unclear. Thus, we have investigated HBQ precursors in plant influents and their removal by each treatment before chlorination in nine DWTPs. The levels of HBQ precursors were determined using formation potential (FP) tests for 2,6-dichloro-1,4-benzoquinone (DCBQ), 2,3,6-trichloro-1,4-benzoquinone (TCBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (DCMBQ), and 2,6-dibromo-1,4-benzoquinone (DBBQ). HBQ precursors were present in all plant influents. DCBQ precursors were the most abundant (DCBQ FP up to 205 ng/L). Coagulation removed dissolved organic carbon (DOC) (up to 56%) and HBQ precursors (up to 39% for DCBQ). The level of removal of DOC was significantly greater than the level of removal of HBQ FP, suggesting that organic matter removed by coagulation had a high proportion of non-HBQ-precursor material. Granular activated carbon (GAC) decreased the level of HBQ FPs by 10-20%, where DOC removal was only 0.2-4.7%, suggesting that the GAC was not in the adsorption mode and biodegradation of HBQ precursors may have been occurring. Ozonation destroyed/transformed HBQ FPs by 10-30%, whereas anthracite/sand filtration and UV irradiation appeared to have no impact. The results demonstrated that the combined treatments did not substantially reduce HBQ precursor levels in water.

  7. Contribution of N-Nitrosamines and Their Precursors to Domestic Sewage by Greywaters and Blackwaters.

    PubMed

    Zeng, Teng; Mitch, William A

    2015-11-17

    N-nitrosamines and their precursors are significant concerns for water utilities exploiting wastewater-impacted water supplies, particularly those practicing potable reuse of wastewater. Previous efforts to identify specific precursors in municipal wastewater accounting for N-nitrosamine formation have met with limited success. As an alternative, we quantified the relative importance of greywater (i.e., shower, kitchen sink, bathroom washbasin, and laundry) and blackwater (i.e., urine and feces) streams in terms of their loadings of ambient specific and total N-nitrosamines and chloramine-reactive and ozone-reactive N-nitrosamine precursors to domestic sewage. Accounting for the volume fractions of individual greywater and blackwater streams, laundry water represented the most significant source of N-nitrosamines and their precursors, followed by shower water and urine. Laundry water was particularly important for ozone-reactive N-nitrosamine precursors, accounting for ∼99% of N-nitrosodimethylamine (NDMA) precursors and ∼69% of precursors for other uncharacterized N-nitrosamines. For the other greywater streams, consumer products contributed additional N-nitrosamines and precursors, but the remarkable uniformity across different products suggested the importance of common macroconstituents. The consumption of a standard dose of the antacid ranitidine substantially increased NDMA and its chloramine-reactive precursors in urine. Nevertheless, nearly 40% of the American population would need to consume ranitidine daily to match the NDMA loadings from laundry water.

  8. Accounting for nonmonotonic precursor duration effects with gain reduction in the temporal window modela

    PubMed Central

    Roverud, Elin; Strickland, Elizabeth A.

    2014-01-01

    The mechanisms of forward masking are not clearly understood. The temporal window model (TWM) proposes that masking occurs via a neural mechanism that integrates within a temporal window. The medial olivocochlear reflex (MOCR), a sound-evoked reflex that reduces cochlear amplifier gain, may also contribute to forward masking if the preceding sound reduces gain for the signal. Psychophysical evidence of gain reduction can be observed using a growth of masking (GOM) paradigm with an off-frequency forward masker and a precursor. The basilar membrane input/output (I/O) function is estimated from the GOM function, and the I/O function gain is reduced by the precursor. In this study, the effect of precursor duration on this gain reduction effect was examined for on- and off-frequency precursors. With on-frequency precursors, thresholds increased with increasing precursor duration, then decreased (rolled over) for longer durations. Thresholds with off-frequency precursors continued to increase with increasing precursor duration. These results are not consistent with solely neural masking, but may reflect gain reduction that selectively affects on-frequency stimuli. The TWM was modified to include history-dependent gain reduction to simulate the MOCR, called the temporal window model-gain reduction (TWM-GR). The TWM-GR predicted rollover and the differences with on- and off-frequency precursors whereas the TWM did not. PMID:24606271

  9. Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

    NASA Technical Reports Server (NTRS)

    Pizzarello, Sandra

    1998-01-01

    Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

  10. Natural attenuation of NDMA precursors in an urban, wastewater-dominated wash.

    PubMed

    Woods, Gwen C; Dickenson, Eric R V

    2016-02-01

    N-Nitrosodimethylamine (NDMA) is a disinfection by-product (DBP) that is potentially carcinogenic and has been found to occur in drinking water treatment systems impacted with treated wastewater. A major gap in NDMA research is an understanding of the persistence of wastewater-derived precursors within the natural environment. This research sought to fill this knowledge gap by surveying NDMA precursors across the length of a wastewater effluent-dominated wash. Significant precursor reduction (17%) was found to occur from introduction into the wash to a point 9 h downstream. This reduction translates into a half-life of roughly 32 h for bulk NDMA precursors. Further laboratory experiments examining rates of photolysis, biodegradation and loss to sediments, illustrated that both photolytic and biological degradation were effective removal mechanisms for NDMA precursors. Loss to sediments that were acquired from the wash did not appear to reduce NDMA precursors in the water column, although a control conducted with DI water provided evidence that significant NDMA precursors could be released from autoclaved sediments (suggesting that sorption does occur). Microbial experiments revealed that microbes associated with sediments were much more effective at degrading precursors than microbes within the water column. Overall, this study demonstrated that natural processes are capable of attenuating NDMA precursors relatively quickly within the environment, and that utilities might benefit from maximizing source water residency time in the environment, prior to introduction into treatment plants.

  11. Novel applications of ceramic precursors -- TiN coating on alumina and functionally gradient materials

    SciTech Connect

    Seyferth, D.; Narula, C.K.; Czubarow, P.

    1996-12-31

    There are very few demonstrated applications of ceramic precursor technology. Here, the authors describe two new applications of known ceramic precursors, thin film deposition and the fabrication of functionally gradient materials (FGM). To demonstrate the thin film deposition, the authors prepared titanium nitride film on an alumina substrate using (CH{sub 3}){sub 3}SiNHTiCl{sub 3} precursor by a single dipcoat-fire cycle. The fabrication of copper and aluminum based FGMs was demonstrated using Nicalon{reg_sign} fiber polycarbosilane and poly(methylsilane) precursors as binders and in situ sources of ceramics.

  12. Spray dried glyceryl monooleate-magnesium trisilicate dry powder as cubic phase precursor.

    PubMed

    Shah, Manish H; Biradar, Shailesh V; Paradkar, Anant R

    2006-10-12

    Glyceryl monooleate (GMO) is a polar amphiphilic lipid, which forms different sequential lyotropic liquid crystals upon hydration. GMO has been utilized for various delivery systems and routes of administrations. Owing to sticky and waxy nature of GMO, preparation of oral solid dosage form utilizing GMO is still a challenge for pharmaceutical researchers. Therefore, the objective of the present work was to fabricate dry powder precursors using GMO, which upon hydration in situ forms cubic phase and can be wisely used for fabrication of oral solid dosage forms. In addition to this, dry powder precursor was evaluated for drug loading, in vitro release behavior and in vivo performance of model drug diclofenac sodium (DiNa). The dry powder precursor was obtained by spray-drying GMO with DiNa using magnesium trisilicate (MTS) as adsorbent. The percent drug entrapment of various batches of powder precursor was in the range of 84-93% indicating high content uniformity. SEM and image analysis showed that as the amount of MTS in powder precursor was increased, the particle size decreased. Furthermore, the viscosity of powder precursor was function of amount of MTS. The rate of water uptake of powder precursor was higher due to uniform layer of GMO on the MTS surface, which led to faster transformation of lamellar phase into cubic phase. The polarizing light microscopy confirmed that cubic phase was formed upon hydration of powder precursor. The drug released from powder precursor was initially governed by the cubic phase formed and in later stage it depends upon dynamic swelling behavior of hexagonally packed cylindrical aggregates. The drug loaded powder precursor was found to have more effective and prolonged anti-inflammatory and analgesic activity as compared to pure drug. Thus the dry powder precursor of cubic phase was prepared in which drug release was entirely governed by the mesophases formed.

  13. Manduca Contactin Regulates Amyloid Precursor Protein-Dependent Neuronal Migration

    PubMed Central

    Ramaker, Jenna M.; Swanson, Tracy L.

    2016-01-01

    Amyloid precursor protein (APP) was originally identified as the source of β-amyloid peptides that accumulate in Alzheimer's disease (AD), but it also has been implicated in the control of multiple aspects of neuronal motility. APP belongs to an evolutionarily conserved family of transmembrane proteins that can interact with a variety of adapter and signaling molecules. Recently, we showed that both APP and its insect ortholog [APPL (APP-Like)] directly bind the heterotrimeric G-protein Goα, supporting the model that APP can function as an unconventional Goα-coupled receptor. We also adapted a well characterized assay of neuronal migration in the hawkmoth, Manduca sexta, to show that APPL–Goα signaling restricts ectopic growth within the developing nervous system, analogous to the role postulated for APP family proteins in controlling migration within the mammalian cortex. Using this assay, we have now identified Manduca Contactin (MsContactin) as an endogenous ligand for APPL, consistent with previous work showing that Contactins interact with APP family proteins in other systems. Using antisense-based knockdown protocols and fusion proteins targeting both proteins, we have shown that MsContactin is selectively expressed by glial cells that ensheath the migratory neurons (expressing APPL), and that MsContactin–APPL interactions normally prevent inappropriate migration and outgrowth. These results provide new evidence that Contactins can function as authentic ligands for APP family proteins that regulate APP-dependent responses in the developing nervous system. They also support the model that misregulated Contactin–APP interactions might provoke aberrant activation of Goα and its effectors, thereby contributing to the neurodegenerative sequelae that typify AD. SIGNIFICANCE STATEMENT Members of the amyloid precursor protein (APP) family participate in many aspects of neuronal development, but the ligands that normally activate APP signaling have remained

  14. Electric earthquake precursors: from laboratory results to field observations.

    NASA Astrophysics Data System (ADS)

    Vallianatos, F.; Triantis, D.; Tzanis, A.; Anastasiadis, C.; Stavrakas, I.

    2003-04-01

    The possibility of electrical earthquake precursors (EEP) has long been appreciated, but it has proven difficult to construct a solid theory to describe their generation and expected characteristics, or proven techniques to identify and discriminate true precursors from noise. To this end, a large number of laboratory experiments have been conducted, which have demonstrated the generation of transient electric potential prior to rupture in both dry and wet rock specimens. The principal mechanisms proposed to explain these observations are the piezo-electric and electrokinetic effects. The often quoted in the literature piezoelectric effect, cannot explain why non-piezoelectric rock specimens can also generate precursory electric phenomena. Streaming potential can be generated in many kinds of saturated rocks, but the fracturing of dry rocks also produces transient electric effects. Therefore, these two mechanisms may not be the basic contributors to the precursory phenomena observed in the laboratory (and to possible EEP signals). Herein we present a series of laboratory experiments on the microfracturing electrification of dry marble samples under stress, and discuss their possible relationship to field observations of purported EEP. The marble samples were subjected to constant and variable stress-rate uniaxial compression, in both the elastic and the plastic region. During the experiment, pressure stimulated currents (PSC) were observed, which show a clear dependence on the stress rate and mechanical state of the material (the Young modulus), decreasing in frequency and intensity with increasing damage during repeated loading cycles. Explanation of these observations is attempted with a theoretical model involving microfracturing and the motion of charged edge dislocations (MCD) as the primary electrification mechanism, after Tzanis and Vallianatos (Seismo Electromagnetics: Lithosphere-Atmosphere-Ionosphere Coupling, TERRAPUB, 2002). The PSC waveforms and mode

  15. Synthesis of functional aromatic multisulfonyl chlorides and their masked precursors.

    PubMed

    Percec, V; Bera, T K; De, B B; Sanai, Y; Smith, J; Holerca, M N; Barboiu, B; Grubbs, R B; Fréchet, J M

    2001-03-23

    The synthesis of functional aromatic bis(sulfonyl chlorides) containing an acetophenone and two sulfonyl chloride groups, i.e., 3,5-bis[4-(chlorosulfonyl)phenyl]-1-acetophenone (16), 3,5-bis(chlorosulfonyl)-1-acetophenone (17), and 3,5-bis(4-(chlorosulfonyl)phenyloxy)-1-acetophenone (18) via a sequence of reactions, involving in the last step the quantitative oxidative chlorination of S-(aryl)- N,N'-diethylthiocarbamate, alkyl- or benzyl thiophenyl groups as masked nonreactive precursors to sulfonyl chlorides is described. A related sequence of reactions was used for the synthesis of the aromatic trisulfonyl chloride 1,1,1-tris(4-chlorosulfonylphenyl)ethane (24). 4-(Chlorosulfonyl)phenoxyacetic acid, 2,2-bis[[[4-(chlorosulfonyl)phenoxyacetyl]oxy]methyl]-1,3-propanediyl ester (27), 5,11,17,23-tetrakis(chlorosulfonyl)-25,26,27,28-tetrakis(ethoxycarbonylmethoxy)calix[4]arene (38), 5,11,17,23,29,35-hexakis(chlorosulfonyl)-37,38,39,40,41,42-hexakis(ethoxycarbonylmethoxy)calix[6]arene (39), 5,11,17,23,29,35,41,47-octakis(chlorosulfonyl)-49,50,51,52,53,54,55,56-octakis(ethoxycarbonylmethoxy)calix[8]arene (40), 5,11,17,23-tetrakis(tert-butyl)-25,26,27,28-tetrakis(chlorosulfonyl phenoxyacetoxy)calix[4]arene (44), 5,11,17,23,29,35-hexakis(tert-butyl)-37,38,39,40,41,42-hexakis(chlorosulfonylphenoxyacetoxy)calix[6]arene (45), and 5,11,17,23,29,35,41,47-octakis(tert-butyl)-49,40,51,52,53,54,55,56-octakis(chlorosulfonylphenoxyacetoxy)calix[8]arene (46) were synthesized by two different multistep reaction procedures, the last step of both methods consisting of the chlorosulfonation of compounds containing suitable activated aromatic positions. 2,4,6-Tris(chlorosulfonyl)aniline (47) was obtained by the chlorosulfonation of aniline. The conformation of two series of multisulfonyl chlorides i.e., 38, 39, 40 and 44, 45, 46, was investigated by (1)H NMR spectroscopy. The masked nonreactive precursor states of the functional aromatic multisulfonyl chlorides and the aromatic

  16. NASA Accident Precursor Analysis Handbook, Version 1.0

    NASA Technical Reports Server (NTRS)

    Groen, Frank; Everett, Chris; Hall, Anthony; Insley, Scott

    2011-01-01

    accident precursors by evaluating anomaly occurrences for their system safety implications and, through both analytical and deliberative methods used to project to other circumstances, identifying those that portend more serious consequences to come if effective corrective action is not taken. APA builds upon existing safety analysis processes currently in practice within NASA, leveraging their results to provide an improved understanding of overall system risk. As such, APA represents an important dimension of safety evaluation; as operational experience is acquired, precursor information is generated such that it can be fed back into system safety analyses to risk-inform safety improvements. Importantly, APA utilizes anomaly data to predict risk whereas standard reliability and PRA approaches utilize failure data which often is limited and rare.

  17. From iron(III) precursor to magnetite and vice versa

    SciTech Connect

    Gotic, M.; Jurkin, T.; Music, S.

    2009-10-15

    The syntheses of nanosize magnetite particles by wet-chemical oxidation of Fe{sup 2+} have been extensively investigated. In the present investigation the nanosize magnetite particles were synthesised without using the Fe(II) precursor. This was achieved by {gamma}-irradiation of water-in-oil microemulsion containing only the Fe(III) precursor. The corresponding phase transformations were monitored. Microemulsions (pH {approx} 12.5) were {gamma}-irradiated at a relatively high dose rate of {approx}22 kGy/h. Upon 1 h of {gamma}-irradiation the XRD pattern of the precipitate showed goethite and unidentified low-intensity peaks. Upon 6 h of {gamma}-irradiation, reductive conditions were achieved and substoichiometric magnetite ({approx}Fe{sub 2.71}O{sub 4}) particles with insignificant amount of goethite particles found in the precipitate. Hydrated electrons (e{sub aq}{sup -}), organic radicals and hydrogen gas as radiolytic products were responsible for the reductive dissolution of iron oxide in the microemulsion and the reduction Fe{sup 3+} {yields} Fe{sup 2+}. Upon 18 h of {gamma}-irradiation the precipitate exhibited dual behaviour, it was a more oxidised product than the precipitate obtained after 6 h of {gamma}-irradiation, but it contained magnetite particles in a more reduced form ({approx}Fe{sub 2.93}O{sub 4}). It was presumed that the reduction and oxidation processes existed as concurrent competitive processes in the microemulsion. After 18 h of {gamma}-irradiation the pH of the medium shifted from the alkaline to the acidic range. The high dose rate of {approx}22 kGy/h was directly responsible for this shift to the acidic range. At a slightly acidic pH a further reduction of Fe{sup 3+} {yields} Fe{sup 2+} resulted in the formation of more stoichiometric magnetite particles, whereas the oxidation conditions in the acidic medium permitted the oxidation Fe{sup 2+} {yields} Fe{sup 3+}. The Fe{sup 3+} was much less soluble in the acidic medium and it hydrolysed

  18. Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα

    PubMed Central

    Mockett, Bruce G.; Richter, Max; Abraham, Wickliffe C.; Müller, Ulrike C.

    2017-01-01

    Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory. While most early studies have been conducted in vitro, effectiveness in animal models is now being confirmed. These studies have revealed that either upregulating α-secretase activity, acutely administering APPsα or chronic delivery of APPsα via a gene therapy approach can effectively treat mouse models of Alzheimer’s disease (AD) and other disorders such as traumatic head injury. Together these findings suggest the need for intensifying research efforts to harness the therapeutic potential of this multifunctional protein. PMID:28223920

  19. Veterinary antibiotics used in animal agriculture as NDMA precursors.

    PubMed

    Leavey-Roback, Shannon L; Krasner, Stuart W; Suffet, Irwin Mel H

    2016-12-01

    The formation of carcinogenic N-nitrosodimethylamine (NDMA) during chloramination at drinking water treatment plants has raised concerns as more plants have switched from chlorine to chloramine disinfection. In this study, a source of NDMA precursors that has yet to be investigated was examined. Veterinary antibiotics are used in large quantities at animal agricultural operations. They may contaminate drinking water sources and may not be removed during wastewater and drinking water treatment. Ten antibiotics used in animal agriculture were shown to produce NDMA or N-nitrosodiethylamine (NDEA) during chloramination. Molar conversions ranged from 0.04 to 4.9 percent, with antibiotics containing more than one dimethylamine (DMA) functional group forming significantly more NDMA. The highest formation for most of the compounds was seen near pH 8.4, in a range of pH 6 to 11 that was investigated. The effect of chlorine-to-ammonia ratio (Cl2/NH3), temperature, and hold time varied for each chemical, suggesting that the effects of these parameters were compound-specific.

  20. Selective Behaviour of Honeybees in Acquiring European Propolis Plant Precursors.

    PubMed

    Isidorov, Valery A; Bakier, Sławomir; Pirożnikow, Ewa; Zambrzycka, Monika; Swiecicka, Izabela

    2016-06-01

    Honey bees harvest resins from various plant species and use them in the hive as propolis. While there have been a number of studies concerning the chemical composition of this antimicrobial product, little is known about selective behavior and bee preference when different potential plant sources of resin are available. The main objective of this paper was to investigate some aspects of behavioral patterns of honeybees in the context of resin acquisition. Samples of propolis originating from temperate zones of Europe and the supposed botanical precursors of the product were analyzed. Taxonomical markers of bud resins of two white birch species, aspen, black poplar, horse-chestnut, black alder, and Scots pine were determined through GC-MS analysis. All these trees have been reported as sources of propolis, but comparisons of the chemical composition of their bud resins with the compositions of propolis samples from seven European countries have demonstrated the presence of taxonomical markers only from black poplar, aspen, and one species of birch. This suggests selective behavior during the collection of bud resins by honeybees. To examine the causes of such selectivity, the antimicrobial properties of bud resins were determined. Horse-chestnut resins had lower antimicrobial activity than the other resins which did not differ significantly.

  1. Sentinel-5 Precursor: Preparing the first Copernicus Atmospheric Mission

    NASA Astrophysics Data System (ADS)

    Nett, Herbert; McMullan, Kevin; Ingmann, Paul; Fehr, Thorsten

    2015-11-01

    Sentinel-5 Precursor (S-5P) will be the first of a series of atmospheric missions to be launched within the European Commission's Copernicus (former GMES) Programme. With a planned launch in 2016 and a nominal lifetime of 7 years S-5P is expected to provide continuity in the availability of global atmospheric data products between its predecessor missions SCIAMACHY (Envisat) and OMI (AURA) and the future Sentinel-4 and -5 series. The latter will comprise payload instruments on board the operational satellites MTG-S (S-4, geostationary component) and MetOp Second Generation (S-5, polar orbiting component), the first units of which will be launched in the 2020-2021 timeframe. The S-5P satellite will carry a single payload, TROPOMI (TROPOspheric Monitoring Instrument) which is jointly developed by The Netherlands and ESA. Covering spectral channels in the UV, visible, near- and short-wave infrared it will measure various key species including tropospheric/stratospheric ozone, NO2, SO2, CO, CH4, CH2O as well as cloud and aerosol parameters.

  2. Neurotransmitter-precursor-supplement intervention for detoxified heroin addicts.

    PubMed

    Chen, Dingyan; Liu, Yan; He, Wulong; Wang, Hongxing; Wang, Zengzhen

    2012-06-01

    This study examined the effects of combined administration of tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan (5-HTP) on heroin withdrawal syndromes and mental symptoms in detoxified heroin addicts. In the cluster-randomized placebo-controlled trial, 83 detoxified heroin addicts were recruited from a detoxification treatment center in Wuhan, China. Patients in the intervention group (n=41) were given the combined treatment with tyrosine, lecithin, L-glutamine and 5-HTP and those in the control group (n=42) were administered the placebo. The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention. The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group. A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group (all P<0.05). It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients' recovery from heroin addiction.

  3. Preparation of hyaluronan polyaldehyde-a precursor of biopolymer conjugates.

    PubMed

    Šedová, Petra; Buffa, Radovan; Kettou, Sofiane; Huerta-Angeles, Gloria; Hermannová, Martina; Leierová, Veronika; Šmejkalová, Daniela; Moravcová, Martina; Velebný, Vladimír

    2013-04-19

    Native hyaluronan (HA) has been oxidized to polyaldehyde polymers with a degree of substitution (DS) of up to 50%. Two different procedures enabling the control of the degree of substitution were followed in this study. Selective oxidation of primary hydroxyl groups of N-acetyl-D-glucosamine of hyaluronan was performed either in an aqueous solution containing AcNH-TEMPO/NaBr/NaOCl or in an aprotic solvent containing Dess-Martin periodinane (DMP). It was found that a change of reaction parameters (reaction time and temperature, type of catalyst, oxidant-to-HA ratio, presence of nitrogen, buffer type, and concentration) had an influence on the degree of substitution and molecular weight. The derivatives were characterized by MS, NMR spectroscopy, and SEC-MALLS. Degradation of hyaluronic acid by the oxidant was observed and confirmed by SEC. The effect of oxidized derivatives of hyaluronan on cells was studied by means of NIH 3T3 fibroblast viability, which indicates that prepared hyaluronan polyaldehydes are biocompatible and suitable for medical applications and tissue engineering. The function of polyaldehyde as precursor for other modification was illustrated in the reaction with lysine.

  4. Comparative investigation of B-Protein and its probable precursor

    SciTech Connect

    Schweikert, A.; Bucovaz, E.

    1987-05-01

    B-Protein, discovered in 1976 by Bucovaz, appears to be a general biological marker for the detection of cancer. An assay procedure was developed to detect B-Protein which involves the interaction of B-Protein with a specific radiolabeled protein named binding protein, a substructure of the coenzyme A-synthesizing protein complex (CoA-SPC) of Bakers' yeast. A protein which may be the precursor of B-Protein is present normally in serum, whereas, a modified or altered protein, designated B-Protein, is present in the serum of cancer patients. Analysis of B-Protein and its relationship with the normal serum protein demonstrates a difference in solubility between B-Protein and the normal counterpart. Although physiochemical characteristics between both are very similar, i.e., electrophoretic mobility, molecular weight, pI, immunological recognition, there appears to be minor differences in the carbohydrate moiety of B-Protein as demonstrated by periodic acid-Schiff base staining and the binding of Wheat Germ Lectin. Lipid content has also been examined but has not been associated with the difference in solubility. Currently, the difference in B-Protein and its normal protein counterpart appears to be related to conformational differences in the tertiary structures.

  5. Photovoltaic lithium-ion battery fabricated by molecular precursor method

    NASA Astrophysics Data System (ADS)

    Nagai, Hiroki; Suzuki, Tatsuya; Takahashi, Yoshihisa; Sato, Mitsunobu

    2016-06-01

    A novel thin-film lithium-ion battery (LIB) which can be charged by the light irradiation was fabricated by molecular precursor method. The unprecedented, translucent thin-film LIB, fabricated on a fluorine-doped tin oxide pre-coated glass substrate, was attained by using the active materials, titania for anode and LiCoO2 for cathode, respectively. The averaged potential at 2.04V was observed by applying a constant current of 0.2mA. Then, that at 1.82V was detected after 60s during the sequential self-discharge process. The charging voltage of the assembled battery was 1.38V with irradiation of 1-sun, the self-discharge voltage was 1.37V. Based on the calibration curve of the charging voltages over constant currents ranging from 0-1.0mA, the detected value can be theoretically reduced to the charging operation by applying a constant current of approximately 60μA. The charge and discharge of this device was stable voltage at least 30 cycles. The two-in-one device can simultaneously generate and store electricity from solar light, the renewable energy source, and may be applied in smart windows for distributed power system according to on-site demand.

  6. Oligodendrocyte precursor cells generate pituicytes in vivo during neurohypophysis development.

    PubMed

    Virard, Isabelle; Coquillat, Delphine; Bancila, Mircea; Kaing, Sovann; Durbec, Pascale

    2006-02-01

    In the vertebrate brain, much remains to be understood concerning the origin of glial cell diversity and the potential lineage relationships between the various types of glia. Besides astrocytes and myelin-forming oligodendrocytes, other macroglial cell populations are found in discrete areas of the central nervous system (CNS). They share functional features with astrocytes and oligodendrocytes but also display specific characteristics. Such specialized cells, called pituicytes, are located in the neurohypophysis (NH). Our work focuses on the lineage of the pituicytes during rodent development. First, we show that cells identified with a combination of oligodendrocyte precursor cell (OPC) markers are present in the developing rat NH. In culture, neonatal NH progenitors also share major functional characteristics with OPCs, being both migratory and bipotential, i.e. able to give rise to type 2 astrocytes and oligodendrocytes. We then observe that, either in vitro or after transplantation into myelin-deficient Shiverer brain, pieces of NH generate myelinating oligodendrocytes, confirming the oligodendrogenic potentiality of NH cells. However, no mature oligodendrocyte can be found in the NH. This led us to hypothesize that the OPCs present in the developing NH might be generating other glial cells, especially the pituicytes. Consistent with this hypothesis, the OPCs appear during NH development before pituicytes differentiate. Finally, we establish a lineage relationship between olig1+ cells, most likely OPCs, and the pituicytes by fate-mapping experiments using genetically engineered mice. This constitutes the first demonstration that OPCs generate glial cells other than oligodendrocytes in vivo.

  7. Silicon deposition in nanopores using a liquid precursor

    NASA Astrophysics Data System (ADS)

    Masuda, Takashi; Tatsuda, Narihito; Yano, Kazuhisa; Shimoda, Tatsuya

    2016-11-01

    Techniques for depositing silicon into nanosized spaces are vital for the further scaling down of next-generation devices in the semiconductor industry. In this study, we filled silicon into 3.5-nm-diameter nanopores with an aspect ratio of 70 by exploiting thermodynamic behaviour based on the van der Waals energy of vaporized cyclopentasilane (CPS). We originally synthesized CPS as a liquid precursor for semiconducting silicon. Here we used CPS as a gas source in thermal chemical vapour deposition under atmospheric pressure because vaporized CPS can fill nanopores spontaneously. Our estimation of the free energy of CPS based on Lifshitz van der Waals theory clarified the filling mechanism, where CPS vapour in the nanopores readily undergoes capillary condensation because of its large molar volume compared to those of other vapours such as water, toluene, silane, and disilane. Consequently, a liquid-specific feature was observed during the deposition process; specifically, condensed CPS penetrated into the nanopores spontaneously via capillary force. The CPS that filled the nanopores was then transformed into solid silicon by thermal decomposition at 400 °C. The developed method is expected to be used as a nanoscale silicon filling technology, which is critical for the fabrication of future quantum scale silicon devices.

  8. [Utilization of melanin precursors for experimental chemotherapy of malignant melanoma].

    PubMed

    Jimbow, K; Miura, S; Ito, Y; Kasuga, T; Ito, S

    1984-10-01

    Melanin synthesis is a metabolic pathway unique and specific to melanocytes. It occurs by conversion of tyrosine to dopa and dopaquinone in the presence of tyrosinase. It is highly accelerated in malignant melanoma with a marked increase of tyrosinase activity. This study summarizes the recent progress in experimental chemotherapeutic approaches to malignant melanoma by utilizing melanin precursors, and presents our current results. Our studies indicated (a) that hydroquinone and 4-isopropylcatechol are selectively toxic to melanocytes and melanoma cells, (b) that their actions are mediated through tyrosinase, and (c) that dopa is selectively and highly incorporated into melanoma cells and melanocytes depending on the tyrosinase activity. In addition, our new compounds, i.e., 4-S-cysteinylphenol and 4-S-cysteaminylphenol were highly toxic to melanoma cells, increasing the life span of B16 melanoma bearing mice and decreasing melanoma growth in C57 BL mice. Other synthetic compounds, e.g., cysteinylcatechols and their devivatives, were, however, not toxic to melanoma cells. 4-S-cysteinylphenol and 4-S-cysteaminylphenol appeared to exert their cytotoxicity through the action of tyrosinase present in melanoma cells, thus providing a kind of "guided missile" approach to melanoma chemotherapy.

  9. Amyloid precursor protein at node of Ranvier modulates nodal formation

    PubMed Central

    Xu, De-En; Zhang, Wen-Min; Yang, Zara Zhuyun; Zhu, Hong-Mei; Yan, Ke; Li, Shao; Bagnard, Dominique; Dawe, Gavin S; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2014-01-01

    Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination. PMID:25482638

  10. LISA and its in-flight test precursor SMART-2

    NASA Astrophysics Data System (ADS)

    Vitale, S.; Bender, P.; Brillet, A.; Buchman, S.; Cavalleri, A.; Cerdonio, M.; Cruise, M.; Cutler, C.; Danzmann, K.; Dolesi, R.; Folkner, W.; Gianolio, A.; Jafry, Y.; Hasinger, G.; Heinzel, G.; Hogan, C.; Hueller, M.; Hough, J.; Phinney, S.; Prince, T.; Richstone, D.; Robertson, D.; Rodrigues, M.; Rüdiger, A.; Sandford, M.; Schilling, R.; Shoemaker, D.; Schutz, B.; Stebbins, R.; Stubbs, C.; Sumner, T.; Thorne, K.; Tinto, M.; Touboul, P.; Ward, H.; Weber, W.; Winkler, W.

    2002-07-01

    LISA will be the first space-home gravitational wave observatory. It aims to detect gravitational waves in the 0.1 mHz÷1 Hz range from sources including galactic binaries, super-massive black-hole binaries, capture of objects by super-massive black-holes and stochastic background. LISA is an ESA approved Cornerstone Mission foreseen as a joint ESA-NASA endeavour to be launched in 2010-11. The principle of operation of LISA is based on laser ranging of test-masses under pure geodesic motion. Achieving pure geodesic motion at the level requested for LISA, 3×10 -15 ms -2/√Hz at 0.1 mHz, is considered a challenging technological objective. To reduce the risk, both ESA and NASA are pursuing an in-flight test of the relevant technology. The goal of the test is to demonstrate geodetic motion within one order of magnitude from the LISA performance. ESA has given this test as the primary goal of its technology dedicated mission SMART-2 with a launch in 2006. This paper describes the basics of LISA, its key technologies, and its in-flight precursor test on SMART-2.

  11. THE EFFECT OF A COSMIC RAY PRECURSOR IN SN 1006?

    SciTech Connect

    Rakowski, Cara E.; Laming, J. Martin; Hwang, Una; Eriksen, Kristoffer A.; Hughes, John P.; Ghavamian, Parviz

    2011-07-01

    Like many young supernova remnants, SN 1006 exhibits what appear to be clumps of ejecta close to or protruding beyond the main blast wave. In this Letter, we examine three such protrusions along the east rim. They are semi-aligned with ejecta fingers behind the shock-front and exhibit emission lines from O VII and O VIII. We first interpret them in the context of an upstream medium modified by the saturated non-resonant Bell instability which enhances the growth of Rayleigh-Taylor instabilities when advected post-shock. We discuss their apparent periodicity if the spacing is determined by properties of the remnant or by a preferred size scale in the cosmic ray precursor. We also briefly discuss the alternative that these structures have an origin in the ejecta structure of the explosion itself. In this case, the young evolutionary age of SN 1006 would imply density structure within the outermost layers of the explosion with potentially important implications for deflagration and detonation in thermonuclear supernova explosion models.

  12. Sustainable Life Cycles of Natural-Precursor-Derived Nanocarbons.

    PubMed

    Bazaka, Kateryna; Jacob, Mohan V; Ostrikov, Kostya Ken

    2016-01-13

    Sustainable societal and economic development relies on novel nanotechnologies that offer maximum efficiency at minimal environmental cost. Yet, it is very challenging to apply green chemistry approaches across the entire life cycle of nanotech products, from design and nanomaterial synthesis to utilization and disposal. Recently, novel, efficient methods based on nonequilibrium reactive plasma chemistries that minimize the process steps and dramatically reduce the use of expensive and hazardous reagents have been applied to low-cost natural and waste sources to produce value-added nanomaterials with a wide range of applications. This review discusses the distinctive effects of nonequilibrium reactive chemistries and how these effects can aid and advance the integration of sustainable chemistry into each stage of nanotech product life. Examples of the use of enabling plasma-based technologies in sustainable production and degradation of nanotech products are discussed-from selection of precursors derived from natural resources and their conversion into functional building units, to methods for green synthesis of useful naturally degradable carbon-based nanomaterials, to device operation and eventual disintegration into naturally degradable yet potentially reusable byproducts.

  13. Sentinel-5 Precursor: First Copernicus Atmospheric Mission Ready for Launch

    NASA Astrophysics Data System (ADS)

    McMullan, Kevin; Nett, Herbert; Fehr, Thorsten; Ingmann, Paul

    2016-08-01

    Sentinel-5 Precursor (S-5P) will be the first of a series of atmospheric missions to be launched within the European Commission's Copernicus (former GMES) Programme. With the current launch window mid October - mid November 2016 and a nominal lifetime of 7 years S-5P is expected to provide continuity in the availability of global atmospheric data products between its predecessor missions SCIAMACHY (Envisat) and OMI (AURA) and the future Sentinel-4 and -5 series.S-5P will deliver unique data regarding the sources and sinks of trace gases with a focus on the lower Troposphere including the planet boundary layer. Due to its enhanced spatial, temporal and spectral sampling capabilities, as compared to its predecessors.The S-5P satellite will carry a single payload, TROPOMI (TROPOspheric Monitoring Instrument) which is jointly developed by The Netherlands and ESA. Covering spectral channels in the UV, visible, near- and short-wave infrared it will measure various key species including tropospheric/stratospheric ozone, NO2, SO2, CO, CH4, CH2O as well as cloud and aerosol parameters.The S-5P Project has successfully passed the Ground Segment Acceptance Review (GS-AR) and the satellite level Qualification Acceptance Review (QAR) in March and April 2016, respectively. Remaining pre-launch tasks focus on the detailed planning of Phase E1 activities and the training of the operations teams.

  14. Transmembrane transport of peptidoglycan precursors across model and bacterial membranes.

    PubMed

    van Dam, Vincent; Sijbrandi, Robert; Kol, Matthijs; Swiezewska, Ewa; de Kruijff, Ben; Breukink, Eefjan

    2007-05-01

    Translocation of the peptidoglycan precursor Lipid II across the cytoplasmic membrane is a key step in bacterial cell wall synthesis, but hardly understood. Using NBD-labelled Lipid II, we showed by fluorescence and TLC assays that Lipid II transport does not occur spontaneously and is not induced by the presence of single spanning helical transmembrane peptides that facilitate transbilayer movement of membrane phospholipids. MurG catalysed synthesis of Lipid II from Lipid I in lipid vesicles also did not result in membrane translocation of Lipid II. These findings demonstrate that a specialized protein machinery is needed for transmembrane movement of Lipid II. In line with this, we could demonstrate Lipid II translocation in isolated Escherichia coli inner membrane vesicles and this transport could be uncoupled from the synthesis of Lipid II at low temperatures. The transport process appeared to be independent from an energy source (ATP or proton motive force). Additionally, our studies indicate that translocation of Lipid II is coupled to transglycosylation activity on the periplasmic side of the inner membrane.

  15. Dry Powder Precursors of Cubic Liquid Crystalline Nanoparticles (cubosomes)

    NASA Astrophysics Data System (ADS)

    Spicer, Patrick T.; Small, William B.; Small, William B.; Lynch, Matthew L.; Burns, Janet L.

    2002-08-01

    Cubosomes are dispersed nanostructured particles of cubic phase liquid crystal that have stimulated significant research interest because of their potential for application in controlled-release and drug delivery. Despite the interest, cubosomes can be difficult to fabricate and stabilize with current methods. Most of the current work is limited to liquid phase processes involving high shear dispersion of bulk cubic liquid crystalline material into sub-micron particles, limiting application flexibility. In this work, two types of dry powder cubosome precursors are produced by spray-drying: (1) starch-encapsulated monoolein is produced by spray-drying a dispersion of cubic liquid crystalline particles in an aqueous starch solution and (2) dextran-encapsulated monoolein is produced by spray-drying an emulsion formed by the ethanol-dextran-monoolein-water system. The encapsulants are used to decrease powder cohesion during drying and to act as a soluble colloidal stabilizer upon hydration of the powders. Both powders are shown to form (on average) 0.6 μm colloidally-stable cubosomes upon addition to water. However, the starch powders have a broader particle size distribution than the dextran powders because of the relative ease of spraying emulsions versus dispersions. The developed processes enable the production of nanostructured cubosomes by end-users rather than just specialized researchers and allow tailoring of the surface state of the cubosomes for broader application.

  16. Synthesis of 9-oxononanoic acid, a precursor for biopolymers.

    PubMed

    Otte, Konrad B; Kirtz, Marko; Nestl, Bettina M; Hauer, Bernhard

    2013-11-01

    Polymers based on renewable resources have become increasingly important. The natural functionalization of fats and oils enables an easy access to interesting monomeric building blocks, which in turn transform the derivative biopolymers into high-performance materials. Unfortunately, interesting building blocks of medium-chain length are difficult to obtain by traditional chemical means. Herein, a biotechnological pathway is established that could provide an environmentally suitable and sustainable alternative. A multiple enzyme two-step one-pot process efficiently catalyzed by a coupled 9S-lipoxygenase (St-LOX1, Solanum tuberosum) and 9/13-hydroperoxide lyase (Cm-9/13HPL, Cucumis melo) cascade reaction is proposed as a potential route for the conversion of linoleic acid into 9-oxononanoic acid, which is a precursor for biopolymers. Lipoxygenase catalyzes the insertion of oxygen into linoleic acid through a radical mechanism to give 9S-hydroperoxy-octadecadienoic acid (9S-HPODE) as a cascade intermediate, which is subsequently cleaved by the action of Cm-9/13HPL. This one-pot process afforded a yield of 73 % combined with high selectivity. The best reaction performance was achieved when lipoxygenase and hydroperoxide lyase were applied in a successive rather than a simultaneous manner. Green leaf volatiles, which are desired flavor and fragrance products, are formed as by-products in this reaction cascade. Furthermore, we have investigated the enantioselectivity of 9/13-HPLs, which exhibited a strong preference for 9S-HPODE over 9R-HPODE.

  17. The p66 Immature Precursor of HIV-1 Reverse Transcriptase

    PubMed Central

    Sharaf, Naima G.; Poliner, Eric; Slack, Ryan L.; Christen, Martin T.; Byeon, In-Ja L.; Parniak, Michael A.; Gronenborn, Angela M.; Ishima, Rieko

    2015-01-01

    In contrast to the wealth of structural data available for the mature p66/p51 heterodimeric human immunodeficiency virus type 1 reverse transcriptase (RT), the structure of the homodimeric p66 precursor remains unknown. In all X-ray structures of mature RT, free or complexed, the processing site in the p66 subunit, for generating the p51 subunit, is sequestered into a β-strand within the folded ribonuclease H (RNH) domain and is not readily accessible to proteolysis, rendering it difficult to propose a simple and straightforward mechanism of the maturation step. Here, we investigated, by solution NMR, the conformation of the RT p66 homodimer. Our data demonstrate that the RNH and Thumb domains in the p66 homodimer are folded and possess conformations very similar to those in mature RT. This finding suggests that maturation models which invoke a complete or predominantly unfolded RNH domain are unlikely. The present study lays the foundation for further in-depth mechanistic investigations at the atomic level. PMID:24771554

  18. Geoelectric potential changes: possible precursors to earthquakes in Japan.

    PubMed

    Uyeda, S; Nagao, T; Orihara, Y; Yamaguchi, T; Takahashi, I

    2000-04-25

    Whether electromagnetic precursors to earthquakes (EQs) exist is an important question not only for EQ prediction but also for understanding the physical processes of EQ generation. Slow transient geoelectric potential changes have been observed before several recent EQs in Japan. In most cases, they appeared 1-19 days before the EQs, and their duration and intensity were several minutes to 1 h and 1-2 mV/100 m. The changes appeared before five of all six EQs with magnitude >/= 5 that occurred within 20 km of our stations during the observation period. Changes were also detected at greater epicentral distances (up to 75 km) before two other EQs, including one EQ of magnitude 4.7, which was preceded by a signal simultaneously recorded at three widely separated stations. These geoelectric potential changes have been distinguished through the following criteria from a multitude of other changes, which were noise of various origins. (i) The selected changes were proportional in amplitude to the length of the recording station's short ( approximately 100 m) dipoles and were simultaneously detected also on long (1-10 km) dipoles when the latter were in operation. (ii) No such changes occurred during the observation period that were not followed by EQs. Although the EQ precursory nature of these geoelectric potential changes is admittedly unproven, it seems that the present results warrant continued serious research into the occurrence, generation, and transmission of these signals and their possible causal relationship to EQs.

  19. SESAME Opens: A Precursor to Human Asteroid Missions

    NASA Astrophysics Data System (ADS)

    Maiwald, Volker; Marchand, Emilien

    2013-09-01

    A common path for human spaceflight is currently often envisioned to lead to Near Earth Asteroids (NEA) within the next decades. While the goal is clear this is not so true for the targets. Just as unmanned probes investigated the lunar surface before humans ever set foot on our natural satellite, it is advisable - considering the current lack of knowledge about NEAs even mandatory - to send an unmanned mission ahead to conduct measurements in preparation of a human mission. Just as with the moon more than one target area should be investigated, i.e. more than one target asteroid. While many designs for the actual human mission already exist, scenarios for a precursor mission are scarcer. In this paper we present a feasible design for a multi-rendezvous mission to targets suitable for human missions, able to reach up to 5 asteroids with one launch. We will propose a system that will be able to measure various properties of each asteroid, e.g. chemical composition and topography and describe it on a subsystem level, providing mass and power budgets for the whole system. The results show that a spacecraft of about 1,600 kg launch mass and utilizing solar electric propulsion can fly a 5 target mission within 10 years. With a sensitivity analysis we will show the robustness of the design and generally establish the feasibility of such a mission.

  20. Accident sequence precursor analysis level 2/3 model development

    SciTech Connect

    Lui, C.H.; Galyean, W.J.; Brownson, D.A.

    1997-02-01

    The US Nuclear Regulatory Commission`s Accident Sequence Precursor (ASP) program currently uses simple Level 1 models to assess the conditional core damage probability for operational events occurring in commercial nuclear power plants (NPP). Since not all accident sequences leading to core damage will result in the same radiological consequences, it is necessary to develop simple Level 2/3 models that can be used to analyze the response of the NPP containment structure in the context of a core damage accident, estimate the magnitude of the resulting radioactive releases to the environment, and calculate the consequences associated with these releases. The simple Level 2/3 model development work was initiated in 1995, and several prototype models have been completed. Once developed, these simple Level 2/3 models are linked to the simple Level 1 models to provide risk perspectives for operational events. This paper describes the methods implemented for the development of these simple Level 2/3 ASP models, and the linkage process to the existing Level 1 models.