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Gamma-Hydroxybutyrate (GHB)  


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Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) and its metabolic precursor, gamma-butyrolactone (GBL) in rats  

Microsoft Academic Search

Rationale  Gamma-hydroxybutyrate (GHB) is becoming an increasingly popular drug of abuse. Metabolic precursors of GHB, gamma-butyrolactone\\u000a (GBL) and 1,4-butanediol (BDL), are commercially available industrial solvents that may also present potential health risks.\\u000a Relatively little is known about the neurobehavioral effects of GHB and its precursors.\\u000a \\u000a \\u000a \\u000a Objective  The aim of the present investigation was to characterize the discriminative stimulus effects of GHB and

Lisa E. Baker; Timothy J. Van Tilburg; Andrew E. Brandt; Alan Poling



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


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. PMID:17658710

Kankaanpää, Aino; Liukkonen, Raija; Ariniemi, Kari



Effects of gamma-hydroxybutyrate (GHB) and its metabolic precursors on delayed-matching-to-position performance in rats.  


The purpose of the present study was to provide further information about the effects of gamma-hydroxybutyrate (GHB) on memory. Initially, the acute effects of gamma-butyrolactone (GBL, 75-200 mg/kg IP), 1,4-butanediol (1,4-BD, 100-300 mg/kg IP), and ethanol (1.0-3.0 g/kg, oral), as well as GHB (100-300 mg/kg IP), were examined in rats responding under a delayed-matching-to-position (DMTP) procedure with delays from 0 to 32 s. Acute administration of all four drugs reduced the number of trials completed and also reduced accuracy during delay trials, but not during trials without a delay. Some tolerance developed to the disruptive effects of GHB following exposure to 300 mg/kg/day for 29 consecutive days. These data indicate that GHB can disrupt working memory and speed of responding, and that tolerance can develop to these effects. Moreover, the acute effects of GHB under the DMTP procedure resemble those of its metabolic precursors, GBL and 1,4-BD, and of the prototypical CNS depressant drug, ethanol. PMID:18201754

Kueh, Daniel; Iwamoto, Kazuhiro; Poling, Alan; Baker, Lisa E



Preference for Gamma-Hydroxybutyrate (GHB) in Current Users  

ERIC Educational Resources Information Center

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…

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



Behavioral effects and pharmacokinetics of gamma-hydroxybutyrate (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons  

PubMed Central

Rationale Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions. Objectives The first study compared the behavioral effects of GBL (32?240 mg/kg) and 1,4-BD (32?240 mg/kg) with each other and to effects previously reported for GHB (32?420 mg/kg). A second study determined GHB pharmacokinetics following intragastric administration of GHB, GBL, and 1,4-BD. Methods Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. In a separate pharmacokinetics study, blood samples were collected across multiple time points after administration of GHB, GBL, and 1,4-BD. Results Like GHB, GBL, and 1,4-BD impaired performance on the fine-motor task, but the onset of motor impairment differed across drugs. GBL and 1,4-BD dose dependently decreased the number of food pellets earned, but at lower doses than previously observed for GHB. Similar to GHB, both GBL and 1,4-BD produced sedation, muscle relaxation, gastrointestinal symptoms, and tremors/jerks. Administration of GBL and 1,4-BD produced higher maximum concentrations of GHB with shorter times to maximum concentrations of GHB in plasma when compared to GHB administration. Conclusions GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB. PMID:19198808

Goodwin, A. K.; Brown, P. R.; Jansen, E. E. W.; Jakobs, C.; Gibson, K. M.; Weerts, E. M.



Preference for Gamma-Hydroxybutyrate (GHB) in Current Users  

PubMed Central

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. PMID:22693361

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




PubMed Central

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

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



GHB (gamma-hydroxybutyrate) carrier-mediated transport across the blood-brain barrier.  


gamma-Hydroxybutyrate (sodium oxybate, GHB) is an approved therapeutic agent for cataplexy with narcolepsy. GHB is widely abused as an anabolic agent, euphoriant, and date rape drug. Recreational abuse or overdose of GHB (or its precursors gamma-butyrolactone or 1,4-butanediol) results in dose-dependent central nervous system (CNS) effects (respiratory depression, unconsciousness, coma, and death) as well as tolerance and withdrawal. An understanding of the CNS transport mechanisms of GHB may provide insight into overdose treatment approaches. The hypothesis that GHB undergoes carrier-mediated transport across the BBB was tested using a rat in situ brain perfusion technique. Various pharmacological agents were used to probe the pharmacological characteristics of the transporter. GHB exhibited carrier-mediated transport across the BBB consistent with a high-capacity, low-affinity transporter; averaged brain region parameters were V(max) = 709 +/- 214 nmol/min/g, K(m) = 11.0 +/- 3.56 mM, and CL(ns) = 0.019 +/- 0.003 cm(3)/min/g. Short-chain monocarboxylic acids (pyruvic, lactic, and beta-hydroxybutyric), medium-chain fatty acids (hexanoic and valproic), and organic anions (probenecid, benzoic, salicylic, and alpha-cyano-4-hydroxycinnamic acid) significantly inhibited GHB influx by 35 to 90%. Dicarboxylic acids (succinic and glutaric) and gamma-aminobutyric acid did not inhibit GHB BBB transport. Mutual inhibition was observed between GHB and benzoic acid, a well known substrate of the monocarboxylate transporter MCT1. These results are suggestive of GHB crossing the BBB via an MCT isoform. These novel findings of GHB BBB transport suggest potential therapeutic approaches in the treatment of GHB overdoses. We are currently conducting "proof-of-concept" studies involving the use of GHB brain transport inhibitors during GHB toxicity. PMID:15173314

Bhattacharya, Indranil; Boje, Kathleen M K



Self-administration of gamma-hydroxybutyric acid (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons  

PubMed Central

Rationale Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse. Objective Given the reports of abuse, and the ease at which GBL and 1,4-BD may be obtained, we investigated the reinforcing of GBL (n=5) and 1,4-BD (n=4) in baboons using IV self-administration procedures. Methods Sessions ran 24 h/day. Each injection was contingent upon completion of a fixed number (120 or 160) of lever responses. A 3-h timeout period followed each injection, limiting the total number of injections to 8/day. Self-administration was first established with cocaine (0.32 mg/kg/injection). GBL (10–130.0 mg/kg/injection), 1,4-BD (10–100 mg/kg/injection) or vehicle were substituted for cocaine at least 15 days. Food pellets were available ad libitum 24 h/day and were contingent upon completion of 10 lever responses. Results GBL (32–100 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in 4 of 5 baboons and mean rates of injection were high (>6 per day) in 3 baboons and moderate in the fourth baboon (4–6 per day). 1,4-BD (78–130 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in only 2 out of 4 baboons and rates were moderate to high in both baboons. Self-injection of these doses of GBL and 1,4-BD generally inhibited food-maintained responding. Conclusions GBL and 1,4-BD have abuse liability. Given that GBL and 1,4-BD are self-administered, are easier to obtain than GHB, and are detected in seized samples, additional legal control measures of these GHB pro-drugs may be needed. PMID:22945514

Goodwin, Amy K.; Kaminski, Barbara J.; Weerts, Elise M.



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


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 ?-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. PMID:25052883

Brennan, Rebekah; Van Hout, Marie Claire



Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine.  


Club drugs are substances commonly used at nightclubs, music festivals, raves, and dance parties to enhance social intimacy and sensory stimulation. The most widely used club drugs are 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy; gamma-hydroxybutyrate (GHB); flunitrazepam (Rohypnol); and ketamine (Ketalar). These drugs are popular because of their low cost and convenient distribution as small pills, powders, or liquids. Club drugs usually are taken orally and may be taken in combination with each other, with alcohol, or with other drugs. Club drugs often are adulterated or misrepresented. Any club drug overdose should therefore be suspected as polydrug use with the actual substance and dose unknown. Persons who have adverse reactions to these club drugs are likely to consult a family physician. Toxicologic screening generally is not available for club drugs. The primary management is supportive care, with symptomatic control of excess central nervous system stimulation or depression. There are no specific antidotes except for flunitrazepam, a benzodiazepine that responds to flumazenil. Special care must be taken for immediate control of hyperthermia, hypertension, rhabdomyolysis, and serotonin syndrome. Severe drug reactions can occur even with a small dose and may require critical care. Club drug over-dose usually resolves with full recovery within seven hours. Education of the patient and family is essential. PMID:15202696

Gahlinger, Paul M



Recordkeeping and reporting requirements for drug products containing gamma-hydroxybutyric acid (GHB). Final rule.  


DEA is amending its regulations to require additional recordkeeping and reporting requirements for drug products containing gamma-hydroxybutyric acid (GHB) for which an application has been approved under the Federal Food, Drug, and Cosmetic Act. DEA makes these changes under section 4 of the "Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000." These additional requirements are necessary to protect against the diversion of GHB for illicit purposes. PMID:15630794



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

PubMed Central

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

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



Symptoms and signs in interpreting Gamma-hydroxybutyrate (GHB) intoxication - an explorative study  

PubMed Central

Background Acute poisoning with gamma-hydroxybutyrate (GHB) has been a serious medical and social problem in different parts of the world including Sweden. GHB is a drug of abuse which acts primarily as central nervous system (CNS) depressants. GHB has serious toxicity, although many young users do not recognise GHB as a dangerous drug. The aim of this pilot study was to explore how symptoms with risk of failure in vital functions would be valued among professionals that encounter GHB intoxication in the emergency phase. Methods A web-based survey focusing on the assessment of vital clinical signs for possible GHB intoxication using a numeric scale was carried out during April and May 2011. The participants, n 105, are all professionals who encounter GHB intoxicated in the emergency phase, but have different levels of training in GHB intoxication, mainly Registered Nurses (RNs) in southwest Sweden, employed in pre-hospital or emergency departments at somatic and most psychiatric health care facilities, as well as police officers who in their work come into contact with drug users. Responses in the survey were scored according to risk of GHB intoxication with serious failure of vital functions. The score value was then referred to a so-called evidence based priority (EBP) scale and analysed using descriptive statistics and Fisher's exact test. Results Cardiac arrest, coma, hypoxia, general convulsions, slow respiratory and heart rate and pale skin are symptoms with the highest risk of serious failure in vital physical functions and were predominantly recognised as such. Conclusion Despite the professionals' different levels of training in GHB intoxication, all of them were relatively well aware of and in accordance regarding the most risky symptoms. The interpretation score for the less risky symptoms and signs of GHB intoxication varied depending on their degree of training. The results should be viewed cautiously, as the size of the professional groups and their general knowledge of critical symptoms of GHB poisoning varied. PMID:24758357



Novel gamma-hydroxybutyric acid (GHB) analogs share some, but not all, of the behavioral effects of GHB and GABAB receptor agonists.  


gamma-Hydroxybutyrate (GHB), a therapeutic for narcolepsy and a drug of abuse, has several mechanisms of action that involve GHB and GABA(B) receptors, metabolism to GABA, and modulation of dopaminergic signaling. The aim of these studies was to examine the role of GHB and GABA(B) receptors in the behavioral effects of GHB. Three approaches were used to synthesize GHB analogs that bind selectively to GHB receptors and are not metabolized to GABA-active compounds. Radioligand binding assays identified UMB86 (4-hydroxy-4-napthylbutanoic acid, sodium salt), UMB72 [4-(3-phenylpropyloxy)butyric acid, sodium salt], UMB73 (4-benzyloxybutyric acid, sodium salt), 2-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid (3-HPA), and 4-hydroxy-4-phenylbutyric acid as compounds that displace [(3)H]NCS-382 [5-[(3)H]-(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7] annulen-6-ylidene) ethanoic acid] from GHB receptors at concentrations that do not markedly affect [(3)H]GABA binding to GABA(B) receptors. In rats and pigeons, GHB discriminative stimulus effects were not mimicked or attenuated by UMB86, UMB72, or 3-HPA up to doses that decreased responding. In mice, GHB, GHB precursors (gamma-butyrolactone and 1,4-butanediol) and GABA(B) receptor agonists [SKF97541 [3-aminopropyl(methyl)phosphinic acid hydrochloride] and baclofen] dose-dependently produced hypolocomotion, catalepsy, ataxia, and loss of righting. The GABA(B) receptor antagonist CGP35348 (3-aminopropyl(diethoxymethyl)phosphinic acid) attenuated catalepsy and ataxia that was observed after GHB and GABA(B) receptor agonists SKF97541 and baclofen. UMB86, UMB72, UMB73, and 3-HPA, like GHB, produced hypolocomotion, ataxia, and loss of righting; however, catalepsy was never observed with these compounds, which is consistent with the cataleptic effects of GHB being mediated by GABA(B) receptors. Ataxia that was observed with UMB86, UMB72, UMB73, and 3-HPA was not antagonized by CGP35348, suggesting that ataxia induced by these analogs is not mediated by GABA(B) receptors and might involve GHB receptors. PMID:15769868

Carter, Lawrence P; Wu, Huifang; Chen, Weibin; Matthews, Marilyn M; Mehta, Ashok K; Hernandez, R Jason; Thomson, Jennifer A; Ticku, Maharaj K; Coop, Andrew; Koek, Wouter; France, Charles P



Comparison of the behavioral effects of gamma-hydroxybutyric acid (GHB) and its 4-methyl-substituted analog, gamma-hydroxyvaleric acid (GHV).  


Gamma-hydroxybutyrate (GHB), a metabolite of GABA, is a drug of abuse and a therapeutic. The illicit use of GHB precursors and analogs reportedly has increased worldwide. Gamma-hydroxyvaleric (GHV) is a 4-methyl-substituted analog of GHB that reportedly is abused and is marketed as a dietary supplement and replacement for GHB. The purpose of these studies was to compare the pharmacological and behavioral profiles of GHV and GHB. In radioligand binding studies, GHV completely displaced [(3)H]NCS-382 with approximately 2-fold lower affinity than GHB and did not markedly displace [(3)H]GABA from GABA(B) receptors at a 20-fold larger concentration. In drug discrimination procedures, GHV did not share discriminative stimulus effects with GHB or baclofen. GHV shared other behavioral effects with GHB, such as sedation, catalepsy, and ataxia, although larger doses of GHV were required to produce these effects. Lethality (50%) was observed after the largest dose of GHV (5600mg/kg), a dose that produced less-than-maximal catalepsy and ataxia. To the extent that large doses of GHV might be taken to in an attempt to produce GHB-like effects (e.g., hypnosis) GHV toxicity may pose a greater public health concern than GHB. PMID:15769562

Carter, Lawrence P; Chen, Weibin; Wu, Huifang; Mehta, Ashok K; Hernandez, R Jason; Ticku, Maharaj K; Coop, Andrew; Koek, Wouter; France, Charles P



A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol.  


We describe a case of withdrawal from the gamma hydroxybutyric acid (GHB) precursors gamma butyrolactone and 1,4-butanediol. Symptoms included visual hallucinations, tachycardia, tremor, nystagmus, and diaphoresis. Administration of benzodiazepines and phenobarbital successfully treated the withdrawal symptoms. As predicted from the metabolism of gamma butyrolactone and 1,4-butanediol to GHB, the symptoms were nearly identical to those reported from GHB withdrawal. Because GHB is now illegal in the United States, individuals have begun abusing the legal and easier to acquire GHB precursors. More frequent cases of both abuse and withdrawal from these GHB precursors can be expected. PMID:11399385

Schneir, A B; Ly, B T; Clark, R F



[Gamma-hydroxybutyrate (GHB) and its lactone (GBL) as psychoactive substances].  


Gammabutyrolactone is included in the solvent such as wheel cleaners, pesticides, cosmetics, drugs. After ingestion GBL is converted to gamma-hydroxybutyrate. Both substances are classified as so called "club drugs" and their action is characterized by euphoria, sedation, and induction of retrograde amnesia of events. These activities were basis for the use of GHB and its lactone as rape pill. Acute poisoning with these compounds causes confusion, agitation, ataxia, nausea, vomiting, nystagmus, dyskinesia, hallucinations, coma, irregular breathing, hypothermia, bradycardia, hypotension, convulsions, respiratory paralysis and thus respiratory arrest. These substances carry a risk of development of physical addiction of the hard proceeding of abstinence syndrome. In the USA there is a ban on the sale and promotion of these compounds. In Poland despite the fact that GHB is a controlled substance, there is no regulation of GBL trading. The aim of this paper is to summarize current knowledge regarding the pharmacology, impact on the human body, toxicity, and the effects of chronic abuse of these substances. PMID:23243924

Krajewska, Anna; Kwiecie?-Obara, Ewelina; Szponar, Jaros?aw; Majewska, Magdalena; Ko?odziej, Ma?gorzata



Withdrawal syndrome from gamma-hydroxybutyric acid (GHB) and 1,4-butanediol (1,4-BD) in Sardinian alcohol-preferring rats.  


Gamma-hydroxybutyric acid (GHB) and its precursors, 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), are recreational drugs widely abused in the US, Europe and Australasia. A severe withdrawal syndrome from GHB, 1,4-BD and GBL has been increasingly documented over the last years, necessitating the development of a reliable animal model for investigations of potential therapeutic approaches. The present study describes the induction and occurrence of audiogenic seizures as a sign of withdrawal from GHB and 1,4-BD in selectively bred Sardinian alcohol-preferring (sP) rats, treated with escalating doses of GHB (1.5-3.5 g/kg, twice daily; i.g.) or 1,4-BD (500-1000 mg/kg, twice daily; i.g.) for 9 consecutive days. Acute administration of the selective GABA(B) receptor antagonist, SCH 50911, dramatically increased seizure occurrence. We propose that the inherent sensitivity of sP rats to different GHB-associated responses may have contributed to the unraveling of a phenomenon which was otherwise not recognizable in other rat strains. PMID:15886053

Carai, Mauro A M; Quang, Lawrence S; Atzeri, Sergio; Lobina, Carla; Maccioni, Paola; Orrù, Alessandro; Gessa, Gian Luigi; Maher, Timothy J; Colombo, Giancarlo



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


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. PMID:23225646

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



Simultaneous analysis of gamma-hydroxybutyric acid and its precursors in urine using liquid chromatography-tandem mass spectrometry.  


We have developed a rapid method that enables the simultaneous analysis of gamma-hydroxybutyrate (GHB) and its precursors, i.e. gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in urine. The method comprised a simple dilution of the urine sample, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Chromatographic separation was achieved using an Atlantis dC18 column, eluted with a mixture of formic acid and methanol. The method was linear from 1-80 mg/L for GHB and 1,4-BD and from 1-50 mg/L for GBL. The limit of quantification was 1 mg/L for all analytes. The procedure, which has a total analysis time (including sample preparation) of less than 12 min, was fully validated and applied to the analysis of 182 authentic urine samples; the results were correlated with a previously published GC-MS procedure and revealed a low prevalence of GHB-positive samples. Since no commercial immunoassay is available for the routine screening of GHB, this simple and rapid method should prove useful to meet the current increased demand for the measurement of GHB and its precursors. PMID:15595536

Wood, Michelle; Laloup, Marleen; Samyn, Nele; Morris, Michael R; de Bruijn, Ernst A; Maes, Robert A; Young, Michael S; Maes, Viviane; De Boeck, Gert



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


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. PMID:24786330

Johansson, Jenny; Grönbladh, Alfhild; Hallberg, Mathias



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

PubMed Central

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

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



Coma and respiratory depression following the ingestion of GHB and its precursors: three cases.  


Gamma hydroxybutyrate (GHB) is a product of the metabolism of both gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Gamma hydroxybutyrate (GHB) is an illegal agent that causes central nervous system depression. Chemical precursors of GHB, such as GBL and 1,4-BD, have been available for purchase from many health food stores and Internet websites for mood-enhancement, sleep-induction, and stimulation of growth hormone release. We report three cases of ingestion of products containing GHB and chemical precursors of GHB. All three patients had severe presentations followed by full recoveries. Some products containing GBL were withdrawn from the market after the FDA issued a warning regarding these products. Products containing 1,4-butanediol remain on the market today. PMID:10863118

Ingels, M; Rangan, C; Bellezzo, J; Clark, R F



[From alcohol to liquid ecstasy (GHB)--a survey of old and modern knockout agents. Part 3: gamma-hydroxybutyric acid ("liquid ecstasy")].  


Currently, gamma-hydroxybutyric acid (GHB/"liquid ecstasy") is frequently abused as a knockout substance. Its detection and the interpretation of the results present numerous problems which are illustrated by case reports. In this context, hair analysis and the increasing significance of gamma-butyrolactone (GBL) are also discussed. PMID:22276366

Schütz, Harald; Jansen, Malin; Verhoff, Marcel A



[Current knowledge on gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL) and 1 ,4-butanediol (1,4-BD)].  


Gamma-hydroxybutyric acid (GHB) is an old anaesthetic drug which was misused in the 80-90's as an anabolic agent (bodybuilding), recreational drug (drunkenness, euphoric, disinhibiting and aphrodisiac effects) and as a date rape drug (disinhibiting, hypnotic and amnesic effects). Its use in the general population is low, and mainly concerns gay population in nightclubs and young people in parties. The intoxications, above all with alcohol combination, can be severe, with coma and breathing depression, or even fatal. Chronic use leads to psychic and physical dependence; withdrawal syndrome can be severe, with agitation and delirium. In 1999, GHB classification as a narcotic resulted in the increased use of GHB prodrugs gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), which were easily commercially available as solvent and cleaning products. Like GHB, they have a narrow window of use, and share similar toxicity. Their increased cases of recreational use and of severe drug intoxication, abuse and dependence, led the French Ministry of Health in 2011 to prohibit their sale and transfer to the public. PMID:22730800

Dematteis, Maurice; Pennel, Lucie; Mallaret, Michel



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


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. PMID:25084768

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



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.  


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. PMID:23104245

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



A Critical Evaluation of the Gamma-Hydroxybutyrate (GHB) Model of Absence Seizures.  


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 ?-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. PMID:25403866

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



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


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 GHB in vitro both 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, although there was no significant increases of GHB levels throughout the period of investigation, the lowest increases were found both in blood and urine at -20°C, therefore we recommend the latter as optimal storage temperature. PMID:25123534

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



Gamma-Hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) reduce the volume of cerebral infarction in rodent transient middle cerebral artery occlusion.  


gamma-Hydroxybutyric acid (GHB), an endogenous organic acid catabolite of gamma-aminobutyric acid (GABA), has been shown to have tissue-protective effects in various organs, including the brain. We examined the potential neuroprotective effect of GHB and its chemical precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), in the rodent ischemic stroke model by intraluminal filament middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats underwent transient left-sided MCAO and received intraperitoneal treatment with 300 mg/kg of GHB, GBL, 1,4-BD, or control vehicle given at 30 min before, as well as 180 and 360 min after the onset of ischemia. Infarct volumes were determined 24 h after MCAO. In transient MCAO, the mean volume of infarction for control rats was 464.4 +/- 17.9 versus 273.6 +/- 53.1, 233.3 +/- 44.7, and 275.4 +/- 39.9 for rats treated with 1,4-BD (P < 0.05), GBL (P < 0.05), and GHB (P < 0.05), respectively. We conclude that GHB, GBL, and 1,4-BD protect against rat focal cerebral ischemia from transient MCAO. PMID:17105951

Sadasivan, Shankar; Maher, Timothy J; Quang, Lawrence S



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


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. PMID:20355156

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



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

PubMed Central

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

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



Discriminative stimulus effects of flumazenil: perceptual masking by baclofen, and lack of substitution with gamma-hydroxybutyrate and its precursors 1,4-butanediol and gamma-butyrolactone.  


Pigeons trained to discriminate 0.1 mg/kg flumazenil, proposed as an in-vivo model to study interactions with diazepam-insensitive gamma-aminobutyric acid (GABA)A receptors, were tested with various GABAergic and non-GABAergic compounds. As a result of its pharmacological selectivity, the model was suitable for further examining previously reported flumazenil-like effects of gamma-hydroxybutyrate (GHB). Flumazenil and the GABAA negative modulator Ro 15-4513 produced 82-100% flumazenil-appropriate responding. Diazepam and the direct-acting GABAA agonists muscimol and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (THIP) produced 38-64% flumazenil-appropriate responding. GHB, its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), and the GABAB agonists baclofen and SKF97541 produced 0-24% flumazenil-appropriate responding. Baclofen shifted the flumazenil dose-response curve to the right and down, possibly involving perceptual masking of the discriminative stimulus effects of flumazenil by agonist activity at GABAB receptors. These masking effects of baclofen were blocked by the GABAB antagonist CGP35348. When CGP35348 was given together with GHB to block its GABAB agonist effects, GHB did not produce flumazenil-appropriate responding. Conceivably, effects of GHB at non-GABAB receptors (e.g. diazepam-sensitive GABAA receptors and GHB receptors) may interfere with the expression of its flumazenil-like discriminative stimulus effects. The asymmetric substitution between GHB and flumazenil is consistent with the hypothesis that the discriminative stimulus effects of GHB consist of several components, not all of which are mimicked by flumazenil. PMID:16572002

Koek, Wouter; Carter, Lawrence P; Wu, Huifang; Coop, Andrew; France, Charles P



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.  


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. PMID:21775083

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



The gamma-hydroxybutyrate withdrawal syndrome.  


gamma-Hydroxybutyrate (GHB) is endogenous inhibitory transmitter that, when administered in pharmacological doses, has sedative-hypnotic properties. It is used in anaesthesia for the treatment of narcolepsy/catalepsy and in alcohol/opioid detoxification treatment regimens. Based on its purported anabolic effects, GHB use became established among bodybuilders. As the euphorigenic effects of GHB became publicised, attendees at dance clubs and rave parties began to use it alone or in combination with other psychoactive drugs. Following the ban of GHB in 1990, several precursor products (e.g. gamma-butyrolactone, butanediol) became widely used as replacement drugs until their ultimate proscription from lawful use in 2000. GHB and its precursors, like most sedative-hypnotic agents, can induce tolerance and produce dependence. Although many GHB users will experience a mild withdrawal syndrome upon drug discontinuation, those with chronic heavy GHB use can experience severe withdrawal. This syndrome clinically resembles the withdrawal syndrome noted from alcohol and other sedative-hypnotic drugs (e.g. benzodiazepines). Distinct clinical features of GHB withdrawal are its relatively mild and brief autonomic instability with prolonged psychotic symptoms. Patients with fulminant GHB withdrawal require aggressive treatment with cross-tolerant sedative hypnotics, such as benzodiazepines. PMID:15298492

Tarabar, Asim F; Nelson, Lewis S



Gamma-hydroxybutyrate, acting through an anti-apoptotic mechanism, protects native and amyloid-precursor-protein-transfected neuroblastoma cells against oxidative stress-induced death.  


Clinical observations suggested that gamma-hydroxybutyrate (GHB) protects nerve cells against death but the direct proofs are missing. Here, we combined several approaches to investigate GHB capacity to protect human neuroblastoma SH-SY5Y cells against hydrogen peroxide (H2O2)-induced death. To increase the patho-physiological relevancy of our study, we used native SH-SY5Y cells and SH-SY5Y cells stably transfected with the wild-type amyloid-precursor-protein (APPwt) or control-vector-pCEP4. Trypan Blue exclusion and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium-bromide) assays combined with pharmacological analyses showed that H2O2 reduced native and genetically modified cell viability and APPwt-transfected cells were the most vulnerable. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and activated caspase-3 staining assessed by flow cytometry revealed a basally elevated apoptotic signal in APPwt-transfected cells. Reverse-transcription, real-time quantitative polymerase chain reaction (qPCR) and Western blotting showed that mRNA and protein basal ratios of apoptotic modulators Bax/Bcl-2 were also high in APPwt-transfected cells. GHB efficiently and dose-dependently rescued native and genetically modified cells from H2O2-induced death. Interestingly, GHB, which strongly decreased elevated basal levels of TUNEL-staining, activated caspase 3-labeling and Bax/Bcl-2 in APPwt-transfected cells, also counteracted H2O2-evoked increased apoptotic markers in native and genetically modified SH-SY5Y cells. Since GHB did not promote cell proliferation, anti-apoptotic action through the down-regulation of Bax/Bcl-2 ratios and/or caspase 3 activity appears as a critical mechanism involved in GHB-induced protection of SH-SY5Y cells against APPwt-overexpression- or H2O2-evoked death. Altogether, these results, providing multi-parametric evidence for the existence of neuroprotective action of GHB, also open interesting perspectives for the development of GHB analog-based strategies against neurodegeneration or nerve cell death. PMID:24456637

Wendt, G; Kemmel, V; Patte-Mensah, C; Uring-Lambert, B; Eckert, A; Schmitt, M J; Mensah-Nyagan, A G



Lack of effects of GHB precursors GBL and 1,4-BD following i.c.v. administration in rats.  


Gamma-hydroxybutyrate (GHB) is used therapeutically and recreationally worldwide. Since the scheduling of GHB by the USA and the United Nations in 2000-2001, the recreational use of GHB precursors has reportedly increased. The aim of this study was to examine if potency differences of GHB and GHB-like compounds are due to their blood-brain barrier permeability. The effects of peripheral and central administration of GHB, GHB precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), and the gamma-aminobutyric acid (GABA)(B) receptor agonist baclofen on schedule-controlled responding were examined in rats. GHB and baclofen were 276- and 253-fold more potent, respectively, after intracerebroventricular (i.c.v.) administration than after intraperitoneal (i.p.) administration, whereas GBL and 1,4-BD, up to a dose of 1780 microg were without effect after i.c.v. administration. These data suggest that GBL and 1,4-BD are not metabolically converted to GHB in the brain, that enhanced brain penetration cannot account for potency differences between compounds, and that baclofen, like GHB, can readily cross the blood-brain barrier. PMID:17100847

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



Enhancement of microcrystalline identification of gamma-hydroxybutyrate.  


An enhancement of the microcrystalline test for the detection of gamma-hydroxybutyrate (GHB) is described. The original test used a silver/copper reagent which consisted of 0.1 g of silver nitrate and 0.1 g of copper nitrate in 10 mL water. The enhanced test utilizes lanthanum nitrate in place of copper nitrate. A detection limit of 0.5 mg/mL was achieved and the visual discrimination was improved because of larger sized crystals. Transient crystals were observed between 0.1 and 0.4 mg/mL. Silver nitrate alone appeared to be suitable for GHB detection but was not specific as other hydroxyl acids, such as glycolic acid, produced a similar crystal pattern. Tests conducted on chemical precursors of GHB and substances with similar biological activity highlight the specificity of the enhanced test. The reagent is therefore selective and sensitive for GHB in aqueous solutions. However, in beverage testing, crystal formation appeared to be inhibited for some drinks. Citric acid was identified as a possible interference depending on its concentration relative to GHB. PMID:18279251

Elie, Mathieu P; Baron, Mark G; Birkett, Jason W



Gamma-butyrolactone and 1,4-butanediol: abused analogues of gamma-hydroxybutyrate.  


gamma-Hydroxybutyrate (GHB) is a GABA-active CNS depressant, commonly used as a drug of abuse. In the early 1990s, the US Drug Enforcement Administration (DEA) warned against the use of GHB and restricted its sale. This diminished availability of GHB caused a shift toward GHB analogues such as gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) as precursors and surrogates. Both GBL and 1,4-BD are metabolically converted to GHB. Furthermore, GBL is commonly used as a starting material for chemical conversion to GHB. As such, the clinical presentation and management of GBL and 1,4-BD intoxication shares a great deal of common ground with that for GHB. This similarity exists not only for acute intoxication but also for withdrawal in those patients with a history of extended high-dose abuse. This review examines the history of GHB analogue abuse as well as the clinical presentation and management of acute intoxication and withdrawal associated with abuse of these compounds. PMID:15298490

Palmer, Robert B



GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid.  


Among the pharmacological actions of gamma-hydroxybutyric acid (GHB), some may involve GABA(A) receptor-mediated mechanisms. GHB, however, fails to directly interact with sites for agonists and modulators on the GABA(A) receptor complex. We hypothesized that, in vivo, GHB may interfere with GABA(A) receptor function by altering the brain concentrations of the neurosteroids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, AP) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, THDOC), positive allosteric modulators of GABA-gated chloride currents. In male Wistar rats, GHB dose-dependently (75-1000 mg/kg, i.p.) increased AP, THDOC and their precursors pregnenolone and progesterone in brain cortex and hippocampus. The increases of AP (4-5 fold) and THDOC (3-4 fold) elicited by 300 mg/kg GHB peaked between 30 and 90 min and abated by 180 min. The selective GABA(B) receptor antagonist SCH 50911 (50 mg/kg, i.p.) prevented the action of GHB, while the GABA(B) receptor agonist baclofen (5-10 mg/kg) mimicked it. NCS-382 (50 mg/kg, i.p.), the purported selective antagonist of the GHB receptor, failed to antagonize GHB, but at 300 mg/kg increased brain cortical neurosteroids to the same extent as 300 mg/kg GHB; coadministration of GHB and NCS-382, however, failed to yield an additive effect. These results strongly suggest that GHB, via a GABA(B) receptor-mediated mechanism, increases the brain concentrations of neurosteroids, whose properties as amplifiers of the GABA-gated chloride conductances may play a role in the GABA(A) receptor-mediated pharmacological actions of GHB. PMID:12015204

Barbaccia, M L; Colombo, G; Affricano, D; Carai, M A M; Vacca, G; Melis, S; Purdy, R H; Gessa, G L



Pharmacological aspects of the combined use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and gamma-hydroxybutyric acid (GHB): a review of the literature.  


Epidemiological studies show that the use of club drugs is on the rise. Furthermore, the last few decades have seen a rise in patterns of polydrug use. One of the combinations frequently used is ecstasy (MDMA) with gammahydroxybutyrate (GHB). For effective prevention it is important to be aware of this phenomenon and of the pharmacology of these drugs. The effects of the combination extend to different neurotransmitter systems, including serotonin, dopamine and noradrenaline. Studies investigating the effects of combinations of psychoactive substances are limited. In this review we describe the subjective effects of the MDMA/GHB combination. Furthermore, we review the individual actions of MDMA on serotonin, dopamine and noradrenaline systems. In addition, actions of GHB on these systems are discussed as a possible pharmacological basis for the interaction of both drugs. It is postulated that GHB attenuates the unpleasant or dysphoric effects of MDMA by its effect on the central dopaminergic system. PMID:16234132

Uys, Joachim D K; Niesink, Raymond J M



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.  


?-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 ?(13)C values, spreading from -24.81‰ to -25.06‰, was observed, whilst mean ?(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 ?(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. PMID:21455654

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



Chronic 1,4-butanediol treatment in rats: cross-tolerance to gamma-hydroxybutyrate and (+/-)-baclofen.  


The effects of 1,4-butanediol, gamma-hydroxybutyrate (GHB), and (+/-)-baclofen on food-maintained responding in rats were assessed before, during, and after chronic treatment with 1,4-butanediol. Six weeks of treatment with 1,4-butanediol (twice daily, 320 mg/kg for 3 weeks followed by 560 mg/kg for 3 weeks) decreased sensitivity to the rate-decreasing effects of (+/-)-baclofen and GHB without changing sensitivity to 1,4-butanediol. Sensitivity to (+/-)-baclofen and GHB returned to control values 2-3 weeks after discontinuation of treatment. These data suggest that tolerance to the effects of GHB or its precursors might result from changes in GABA(B) mechanisms. PMID:14744611

Eckermann, Kary A; Koek, Wouter; France, Charles P



An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results.  


Abuse of gamma-hydroxybutyric acid (GHB) has been known since the early 1990's, but is not as widespread as the consumption of other illegal drugs. However, the number of severe intoxications with fatal outcomes is comparatively high; not the least of which is brought about by the consumption of the currently legal precursor substances gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). In regards to previous assumptions, addiction to GHB or its analogues can occur with severe symptoms of withdrawal. Moreover, GHB can be used for drug-facilitated sexual assaults. Its pharmacological effects are generated mainly by interaction with both GABA(B) and GHB receptors, as well as its influence on other transmitter systems in the human brain. Numerous analytical methods for determining GHB using chromatographic techniques were published in recent years, and an enzymatic screening method was established. However, the short window of GHB detection in blood or urine due to its rapid metabolism is a challenge. Furthermore, despite several studies addressing this problem, evaluation of analytical results can be difficult: GHB is a metabolite of GABA (gamma-aminobutyric acid); a differentiation between endogenous and exogenous concentrations has to be made. Apart from this, in samples with a longer storage interval and especially in postmortem specimens, higher levels can be measured due to GHB generation during this postmortem interval or storage time. PMID:21381220

Andresen, H; Aydin, B E; Mueller, A; Iwersen-Bergmann, S



Gamma-hydroxybutyric acid stability and formation in blood and urine.  


Gamma-hydroxybutyric acid (GHB) can cause problems in interpretation of toxicological findings due to its endogenous nature, significant production in tissues after death and potential formation in stored samples. Our study was designed to determine the influence of storage conditions on GHB levels and its possible in vitro formation in blood and urine in cases where no exogenous use of GHB or its precursors was suspected. The samples were prepared by validated method based on liquid-liquid reextraction with adipic acid internal standard and MSTFA derivatization and assayed on a GC-MS operating in EI SIM mode. The first part of the study was performed with pooled blood and urine samples obtained from living and deceased subjects stored with and without NaF (1% w/v) at 4 and -20 degrees C over 8 months. In ante-mortem samples (both blood and urine) no significant GHB production was found. After 4 months of storage, the substantial GHB rise up to 100 mg/Lwas observed in post-mortem blood stored at 4 degrees C without NaF with subsequent gradual decrease in following months. The inhibition of GHB production was apparent during storage in NaF treated frozen blood samples. In post-mortem urine only slight temporary GHB levels were ascertained (up to 8 mg/L). The second part of our study was aimed to analyse 20 individual post-mortem blood samples stored at 4 degrees C for 16-27 days between autopsy and analysis without preservation followed by storage at 4 degrees C with NaF for 4 months. The temporary GHB production with maximum of 28 mg/Lwas detected in some samples. PMID:16857333

Beránková, Katerina; Mutnanská, Katerina; Balíková, Marie



Failure of gamma-hydroxybutyric acid both to increase neuroactive steroid concentrations in adrenalectomized-orchiectomized rats and to induce tolerance to its steroidogenic effect in intact animals.  


Gamma-Hydroxybutyric acid (GHB), a drug proposed in the treatment of alcohol withdrawal syndrome, increases the cerebrocortical and plasma concentrations of the neuroactive steroids allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC). In the present study, we examined the role of hypothalamic-pituitary-adrenal (HPA) axis in the effect of GHB by measuring the concentrations of these steroids in the brain and plasma of adrenalectomized-orchiectomized (Adx-Orx) rats. The acute administration of GHB (500 mg/kg, i.p.) induced in 30 min an increase in the concentrations of allopregnanolone, THDOC and their precursors pregnenolone and progesterone in different brain areas (cerebral cortex, hypothalamus and cerebellum) and plasma of sham-operated rats but had no effect on the concentrations of these compounds in Adx-Orx rats, suggesting that activation of the HPA axis mediates the effect of GHB on brain and plasma concentrations of neuroactive steroids. Moreover, we evaluated whether repeated exposure of GHB induces tolerance to its steroidogenic effects. Chronic administration of GHB (500 mg/kg, i.p., twice a day for 10 days) to intact animals failed to affect the levels of progesterone, allopregnanolone, or THDOC measured 3 or 48 h after the last drug administration, whereas a challenge injection of GHB or ethanol was still able to increase the concentrations of these steroids in brain and plasma. These results indicate that repeated exposure to GHB fails to induce tolerance or cross-tolerance to the steroidogenic action of GHB or ethanol, respectively. PMID:15158173

Porcu, Patrizia; Sogliano, Cristiana; Ibba, Cristina; Piredda, Massimo; Tocco, Silvia; Marra, Carla; Purdy, Robert H; Biggio, Giovanni; Concas, Alessandra



Increased food intake following the manipulation of intracerebral dopamine levels with gamma-hydroxybutyrate  

Microsoft Academic Search

The administration of gamma-hydroxybutyric acid (GHB) initially causes a temporary “sleep-like” state during which there is an increase in forebrain dopamine levels. The present series of experiments examined whether in the period following the GHB-induced behavioural depression, when accumulated dopamine is dispersed, there is any behavioural evidence of increased dopaminergic activity. The first experiment, in which GHB was injected directly

P. Redgrave; E. B. Taha; L. White; P. Dean



1 -O-alkyl-2-(omega-oxo)acyl-sn-glycerols from shark oil and human milk fat are potential precursors of PAF mimics and GHB.  


This study examines the feasibility that peroxidation and lipolysis of 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGE) found in shark liver oil and human milk fat constitutes a potential source of dietary precursors of platelet activating factor (PAF) mimics and of gamma-hydroxybutyrate (GHB). Purified DAGE were converted into 1-O-alkyl-2-acyl-sn-glycerols by pancreatic lipase, without isomerization, and transformed into 1-O-alkyl-2-oxoacyl-sn-glycerols by mild autooxidation. The various core aldehydes without derivatization, as well as the corresponding dinitrophenylhydrazones, were characterized by chromatographic retention time and diagnostic ions by online electrospray mass spectrometry. Core aldehydes of oxidized shark liver oil yielded 23 molecular species of 1-O-alkyl-sn-glycerols with short-chain sn-2 oxoacyl groups, ranging from 4 to 13 carbons, some unsaturated. Autooxidation of human milk fat yielded 1-O-octadecyl-2-(9-oxo)nonanoyl-sn-glycerol, as the major core aldehyde. Because diradylglycerols with short fatty chains are absorbed in the intestine and react with cytidine diphosphate-choline in the enterocytes, it is concluded that formation of such PAF mimics as 1-O-alkyl-2-(omega-oxo)acyl-sn-glycerophosphocholine from unsaturated dietary DAGE is a realistic possibility. Likewise, a C4 core alcohol produced by aldol-keto reduction of a C4 core aldehyde constitutes a dietary precursor of the neuromodulator and recreational drug GHB, which has not been previously pointed out. PMID:17069352

Hartvigsen, Karsten; Ravandi, Amir; Harkewicz, Richard; Kamido, Hiroshi; Bukhave, Klaus; Hølmera, Gunhild; Kuksis, Arnis



The Discriminative stimulus effects of gamma-hydroxybutyrate and related compounds in rats discriminating baclofen or diazepam: The role of GABA(B) and GABA(A) receptors.  


The discriminative stimulus effects of gamma-hydroxybutyrate (GHB) can be mimicked by GABA(A) receptor-positive modulators (e.g., diazepam) and GABA(B) receptor agonists (e.g., baclofen). The purposes of this study were to see whether stimulus control could be established with baclofen and to further characterize the role of GABAergic mechanisms in the behavioral actions of GHB by evaluating GHB and related compounds in rats discriminating either diazepam or baclofen. Training criteria were satisfied with baclofen and diazepam after 69 and 44 sessions, respectively. GHB and its precursors gamma-butyrolactone and 1,4-butanediol occasioned >80% responding on the drug-associated lever in rats discriminating baclofen and <11% in rats discriminating diazepam. Diazepam and other GABA(A) receptor-positive modulators occasioned intermediate levels of responding on the baclofen lever, whereas baclofen occasioned less than 4% responding on the diazepam lever. The GABA(B) receptor antagonist CGP 35348 [(3-aminopropyl)(diethoxymethyl) phosphinic acid] partially antagonized the effects of baclofen as well as the baclofen-like effects of GHB, and flumazenil partially antagonized the effects of diazepam. This study established stimulus control with baclofen, and substitution data provided direct evidence for a role of GABAergic, especially GABA(B), mechanisms in the discriminative stimulus effects of GHB. The lack of substitution by GHB or its metabolic precursors for diazepam indicates a comparatively smaller role of GABA(A) mechanisms in these effects of GHB. The inability of CGP 35348 to completely attenuate the effects of baclofen and GHB suggests that multiple receptors could be involved in the discriminative stimulus effects of GHB. PMID:14742739

Carter, L P; Unzeitig, A W; Wu, H; Chen, W; Coop, A; Koek, W; France, C P



GHB, GBL and 1,4-BD addiction.  


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. PMID:24001290

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



Discriminative stimulus effects of gamma-hydroxybutyrate in pigeons: role of diazepam-sensitive and -insensitive GABA(A) and GABA(B) receptors.  


gamma-Hydroxybutyrate (GHB) is an emerging drug of abuse with multiple mechanisms of action. This study is part of an effort to examine the role of GHB, GABA(A), and GABA(B) receptors in the discriminative stimulus (DS) effects of GHB. In pigeons trained to discriminate 100 mg/kg GHB from saline, GHB and its precursors gamma-butyrolactone and 1,4-butanediol produced 80 to 100% GHB-appropriate responding, whereas other compounds such as morphine, naltrexone, cocaine, and haloperidol produced no more than 34%. Compounds interacting with GABA receptors produced different maximal levels of GHB-appropriate responding. For example, the GABA(A) agonist muscimol produced 3%; the GABA(A)-positive modulators diazepam, pentobarbital, and ethanol, and the GABA(B) agonist baclofen produced levels ranging from 54 to 73%; and the benzodiazepine antagonist flumazenil and inverse agonist Ro 15-4513 (ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]-benzodiazepine-3-carboxylate) both produced 96%. The putative GHB receptor antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) produced 70% GHB-appropriate responding. The GABA(B) antagonist (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP 35348) completely blocked the GHB-like DS effects of NCS-382 and baclofen at a dose of 56 mg/kg. CGP 35348 also blocked the DS effects of GHB, but incompletely and only at a dose of 560 mg/kg. Together, these results are consistent with a role for diazepam-sensitive and -insensitive GABA(A) and GABA(B) receptors in the DS effects of GHB. Together with previous findings, the present results suggest that diazepam-insensitive GABA(A) receptors are more prominently involved in the DS effects of GHB in pigeons than in rats, whereas GABA(B) receptors are less prominently involved. Exploring the role of GHB receptors with NCS-382 is hampered by its GABA(B) receptor-mediated, GHB-like agonist activity. PMID:14718595

Koek, Wouter; Flores, Lauren R; Carter, Lawrence P; Lamb, R J; Chen, Weibin; Wu, Huifang; Coop, Andrew; France, Charles P



[GHB--dangerous, addictive and uncontrollable "party drug"].  


This report reviews the pharmacology, toxicity and abuse pattern of gamma-hydroxybutyrate (GHB). The legislative changes pertaining to this substance are also addressed. Examples of abuse, driving under the influence and fatal intoxication are given. It is concluded that GHB is widely abused, particularly among the younger generation, and that further cases of severe intoxication are likely to occur as long as the substance is easily available from countless sources, including via the Internet. Despite the classification of GHB as a narcotic in Sweden and several other countries, continued problems are expected since the precursors gamma-butyrolactone (GBL) and 1,4-butanediol (BD) are widely--and legally--available. PMID:11602959

Persson, S A; Eriksson, A; Hallgren, N; Eklund, A; Berkowicz, A; Druid, H



Urinary concentrations of gamma-hydroxybutyric acid and related compounds in pregnancy.  


Endogenous production complicates the interpretation when gamma-hydroxybutyric acid (GHB) is measured in urine for forensic purposes. We performed a cross-sectional study to test the hypothesis that pregnant women have higher levels of urinary GHB than non-pregnant controls, and thus increased risk of false-positive GHB tests. GHB, gamma-butyrolactone (GBL) and beta-hydroxybutyric acid (BHB) concentrations in urine from 66 pregnant women and 69 non-pregnant controls were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The mean GHB, GBL, and BHB concentrations were 0.36, 0.34 and 1.92 mg/L in the pregnant women, and 0.24, 0.08 and 0.40 mg/L in the control group. The pregnant women had significantly higher levels of GHB (1.5-fold), GBL (4.3-fold), and BHB (4.8-fold). Creatinine-adjusted GHB concentrations were similar in both groups. Pregnant women have higher urinary levels of GHB, GBL, and BHB. In LC-MS-MS assays not distinguishing between GHB and BHB, there is a significantly increased risk of false-positive GHB tests in pregnant women. This false-positive rate can be reduced by correcting for creatinine concentration, by using GHB-specific assays or by introducing higher interpretative cut-off levels for pregnant women in assays that do not discriminate between GHB and GBL or BHB. PMID:20822677

Raknes, Guttorm; Aronsen, Lena; Fuskevåg, Ole Martin



Agitation is common in gamma-hydroxybutyrate toxicity.  


Gamma-Hydroxybutyrate (GHB)-related compounds are most commonly described as depressants, with emphasis on somnolence, obtundation, stupor, and coma (SOSC). We sought to demonstrate the full spectrum of clinical presentations of GHB intoxication, including agitation and other nonsedative effects. Our observational study identified 66 patients with GHB toxicity, 40 of whom manifested agitation; 25 had agitation before or after SOSC, 10 had agitation alternating abruptly with SOSC, and 5 had agitation only. Fourteen presentations also included "bizarre" or self-injurious behaviors. Of 40 presentations with agitation, 19 had stimulant co-intoxicants confirmed by screen (14) or history (5). The remaining 21 patients with agitation were negative for stimulants by screen (12) or history (9). Gas chromatography/mass spectrometry detected GHB in 25 cases; 12 manifested agitation, 4 of which also screened negative for stimulants. Clinicians should broaden their definitions of GHB toxicity to include nonsedative effects such as agitation, combativeness, and bizarre or self-injurious behavior. PMID:15915404

Zvosec, Deborah L; Smith, Stephen W



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


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. PMID:15587253

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



GHB: a new and novel drug of abuse.  


There has been increasing attention in the United States to problems of abuse of gamma-hydroxybutyrate (GHB), with some evidence for problems in other parts of the world as well. In vitro and animal research show that, while GHB shares some properties with abused central nervous system depressant drugs, it has unique aspects of its pharmacology as well, including actions at a specific neural receptor which probably mediates many of its effects. Abuse potential assessment of GHB using standard animal models has not yielded a picture of a highly abusable substance, but little human testing has yet been done. Very little systematic data exist on tolerance and dependence with GHB, but both have been seen in human users. Quantitative data on the prevalence of GHB abuse is incomplete, but various qualitative measures indicate that a mini-epidemic of abuse began in the late 1980s and continues to the present. GHB is often included with the group of 'club drugs', and can be used as an intoxicant. It also has been used as a growth promoter and sleep aid and has been implicated in cases of 'date rape', usually in combination with alcohol. Undoubtedly the easy availability of GHB and some of its precursors has contributed to its popularity. Recent changes in the control status of GHB in the US may reduce its availability with as yet unknown consequences for the scope of the public health problem. Drug abuse experts need to familiarize themselves with GHB as possibly representing a new type of drug abuse problem with some unique properties. PMID:11297827

Nicholson, K L; Balster, R L



Simultaneous determination of GHB and EtG in hair using GCMS/MS.  


A gas chromatographic tandem mass spectrometric (GCMS/MS) method for simultaneously determining trace concentrations of gamma-hydroxybutyrate (GHB) and ethyl glucuronide (EtG) in hair has been developed. Multiple reaction monitoring (MRM) was used to detect precursor and product ions of GHB, (233 and 147) and EtG (261 and 143) following anion exchange solid phase extraction and derivatization with N,O-bis[trimethylsilyl]trifluoroacetamide (BSTFA). Deuterated standards of GHB and EtG were used as internal standards. The assay produced excellent linearity (r(2) > 0.99) and sensitivity. The lower limit of quantitation (LLOQ) was 10 pg/mg for EtG assuming a 20 mg hair sample. The method has been used to investigate cases of suspected drug facilitated assault as well as being used to identify heavy alcohol consumption in a group of volunteers. PMID:21500364

Paul, R; Tsanaclis, L; Kingston, R; Berry, A; Guwy, A



Acute poisoning from gamma-hydroxybutyrate in California.  

PubMed Central

We report a series of 5 representative patients in California who experienced adverse reactions from the illicitly marketed substance gamma-hydroxybutyrate (GHB). The drug is a putative neurotransmitter marketed as a growth hormone releaser for bodybuilders. The most commonly reported symptoms included abrupt drowsiness, dizziness, and a "high". Other effects were headache, nausea, vomiting, myoclonic jerking, and short-term coma. There have been no reported deaths. If product use is discontinued, full recovery with no long-term side effects is universal. No clear dose-response effect was observed; this may be attributable to differences in susceptibility, wide variations in doses taken by the same person, or the coingestion of other substances. Case interviews confirm that, despite being banned by the US Food and Drug Administration, GHB is still widely available in the underground drug market. Athletes and bodybuilders may take drugs for which there are claims of improved performance or body image. Physicians should be alert for signs of GHB poisoning in emergency department and clinic patients. PMID:1574880

Chin, M. Y.; Kreutzer, R. A.; Dyer, J. E.



Prodynorphin and proenkephalin mRNAs are increased in rat brain after acute and chronic administration of gamma-hydroxybutyrate.  


The effects of gamma-hydroxybutyrate (GHB) on prodynorphin (PD) and proenkephalin (PE) mRNA expression were examined using in situ hybridization histochemistry in discrete rat brain structures rich in GHB receptors. A single dose of GHB (500 mg/kg i.p.) increased striatal PE mRNA levels (+60%) between 15 and 90 min after injection. An increase in PD mRNA expression was observed in the frontal cortex (+90%) 6 h after GHB administration. Chronic exposure to GHB (500 mg/kg i.p. twice a day) for 10 days induced significant increases in both PE and PD mRNA levels in different brain regions examined, suggesting that PD and PE mRNA expressions are modulated by the endogenous GHBergic system. PMID:10076874

Schmidt-Mutter, C; Gobaille, S; Muller, C; Maitre, M



GABA(B) receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid.  


The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABA(B) receptors (GABA(B)Rs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABA(A) and GABA(B)Rs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABA(B)R agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca(2+) in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABA(B)Rs and mediated by Ca(2+) release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB. PMID:25225100

Gould, Timothy; Chen, Lixin; Emri, Zsuzsa; Pirttimaki, Tiina; Errington, Adam C; Crunelli, Vincenzo; Parri, H Rheinallt



Analysis of Electrical Brain Waves in Neurotoxicology: Gamma-Hydroxybutyrate  

PubMed Central

Advances in computer technology have allowed quantification of the electroencephalogram (EEG) and expansion of quantitative EEG (qEEG) analysis in neurophysiology, as well as clinical neurology, with great success. Among the variety of techniques in this field, frequency (spectral) analysis using Fast Fourier Transforms (FFT) provides a sensitive tool for time-course studies of different compounds acting on particular neurotransmitter systems. Studies presented here include Electrocorticogram (ECoG) analysis following exposure to a glutamic acid analogue - domoic acid (DOM), psychoactive indole alkaloid - ibogaine, as well as cocaine and gamma-hydroxybutyrate (GHB). The ECoG was recorded in conscious rats via a tether and swivel system. The EEG signal frequency analysis revealed an association between slow-wave EEG activity delta and theta and the type of behavioral seizures following DOM administration. Analyses of power spectra obtained in rats exposed to cocaine alone or after pretreatment with ibogaine indicated the contribution of the serotonergic system in ibogaine mediated response to cocaine (increased power in alpha1 band). Ibogaine also lowered the threshold for cocaine-induced electrographic seizures (increased power in the low-frequency bands, delta and theta). Daily intraperitoneal administration of cocaine for two weeks was associated with a reduction in slow-wave ECoG activity 24 hrs following the last injection when compared with controls. Similar decreased cortical activity in low-frequency bands observed in chronic cocaine users has been associated with reduced metabolic activity in the frontal cortex. The FFT analyses of power spectra relative to baseline indicated a significant energy increase over all except beta2 frequency bands following exposure to 400 and 800 mg/kg GHB. The EEG alterations detected in rats following exposure to GHB resemble absence seizures observed in human petit mal epilepsy. Spectral analysis of the EEG signals combined with behavioral observations may prove to be a useful approach in studying chronic exposure to drugs of abuse and treatment of drug dependence. PMID:21886596

Binienda, Z.K; Beaudoin, M.A; Thorn, B.T; Ali, S.F



Determination of GHB and its precursors (GBL and 1,4-BD) in dietary supplements through the synthesis of their isotopologues and analysis by GC-MS method.  


Gamma-hydroxybutyric acid (GHB) and its "pro-drugs", gamma-butyrolactone (GBL) and 1,4 butanediol (1,4-BD), are drugs of abuse with depressant effects on the central nervous system. Many analytical methods have been proposed for the quantitative determination of these compounds mainly in biological matrices but only few have been addressed to dietary supplements and foods. Facile synthesis of the GBL and 1,4-BD isotopologues are available by "one pot" Ru-catalyzed homogeneous deuteration of dicarboxylic acids. In this work we propose a new method for determination of GHB, GBL and 1,4-BD in commercially available dietary supplements, based on isotope dilution mass spectrometry (ID-MS). The procedure involves a simple extraction of sample with acidic acetonitrile and direct analysis by GC-ID-MS method without any purification or derivatization. Indeed, the proposed method takes advantage of the complete conversion of GHB (free acid or its salts) to GBL, allowing the quantification of GHB and its pro-drugs. Five levels for each calibration curve have been prepared by diluting working solutions of the analytes to obtain concentrations ranging from 1 to 20mg/mL. The validation procedures have shown an accuracy between 88% and 99% and a precision between 7.3% and 2.9% of each analyte in the sample matrix. Positive ions chemical ionization (PICI) have been employed to preserve the information on molecular ions and to improve specificity and sensitivity of quantitative determination. PMID:23245230

Rosi, Luca; Frediani, Piero; Bartolucci, Gianluca



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

Code of Federal Regulations, 2012 CFR

...containing gamma-hydroxybutyric acid. 1304.26 Section 1304...containing gamma-hydroxybutyric acid. In addition to the recordkeeping...dispensing gamma-hydroxybutyric acid that is manufactured or distributed...Prescribing practitioner's Federal and State...



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

Code of Federal Regulations, 2011 CFR

...containing gamma-hydroxybutyric acid. 1304.26 Section 1304...containing gamma-hydroxybutyric acid. In addition to the recordkeeping...dispensing gamma-hydroxybutyric acid that is manufactured or distributed...Prescribing practitioner's Federal and State...



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

...containing gamma-hydroxybutyric acid. 1304.26 Section 1304...containing gamma-hydroxybutyric acid. In addition to the recordkeeping...dispensing gamma-hydroxybutyric acid that is manufactured or distributed...Prescribing practitioner's Federal and State...



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

Code of Federal Regulations, 2013 CFR

...containing gamma-hydroxybutyric acid. 1304.26 Section 1304...containing gamma-hydroxybutyric acid. In addition to the recordkeeping...dispensing gamma-hydroxybutyric acid that is manufactured or distributed...Prescribing practitioner's Federal and State...



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

Code of Federal Regulations, 2010 CFR

...containing gamma-hydroxybutyric acid. 1304.26 Section 1304...containing gamma-hydroxybutyric acid. In addition to the recordkeeping...dispensing gamma-hydroxybutyric acid that is manufactured or distributed...Prescribing practitioner's Federal and State...



Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens  

PubMed Central

Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca2+ transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca2+ dynamics evoked by GHB suggested that Ca2+ was released from internal stores. Similarly to SUC, the GHB response was also characterized by an effective concentration of 50??M. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca2+ signal remained in mice lacking GABAB receptor type 1 subunit in the presence and absence of the N-Methyl-d-Aspartate (NMDA) receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV), indicating action mechanisms independent of the GABAB or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252, and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91) also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca2+ signaling in astrocytic networks. PMID:22180742

Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Ágnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna



Potential surrogate markers for gamma-hydroxybutyrate administration may extend the detection window from 12 to 48 hours.  


The exogenous administration of gamma-hydroxybutyrate (GHB) as a drug of abuse, and especially in date rape sexual assaults, has recently increased. Chromatographic techniques are used to detect GHB in blood or urine, with a window of detection limited to 12 h. This brief window makes the proof of administration problematic in most rape cases. This study is aimed to extend the window of detection through surrogate markers of GHB administration. Microarray technology is used in a DBA/2J mouse model to detect gene expression changes in peripheral blood after GHB exposure at times as long as 96 h post exposure. This study focuses on two of the most significantly altered transcripts, epiregulin and phosphoprotein enriched in astrocytes 15 (Pea-15). Both genes have increased the ribonucleic acid expression (8.5- and 4.6-fold upregulation at 96 h, respectively) in GHB-dosed mice (1 g/kg) as compared with the control. To confirm these results at the protein level, an intracellular flow cytometric assay is developed to detect protein level changes in the peripheral blood of both these potential biomarkers after GHB exposure. These results suggest that after further development, epiregulin and Pea-15 may prove to be significant surrogate markers in the indirect detection of GHB administration. PMID:17389079

Larson, Scott J; Putnam, Elizabeth A; Schwanke, Corbin M; Pershouse, Mark A



Stability of plasma gamma-hydroxybutyrate determined by gas chromatography-positive ion chemical ionization-mass spectrometry.  


An effective method for the determination of gamma-hydroxybutyric acid (GHB) in human plasma is described that utilizes a simple liquid-liquid extraction procedure and gas chromatography-positive ion chemical ionization-mass spectrometry (GC-PCI-MS). The method has been used to study the stability of plasma GHB under several storage conditions. Following the extraction with acetonitrile, GHB and deuterated GHB (GHB-d(6)) were derivatized with N,O-bis[trimethylsilyl] trifluoroacetamide (BSFTA). After the separation on a capillary GC column, the derivatives were ionized with ammonia reagent gas and analyzed by MS. The lower limit of quantitation in 100 microL of plasma was 2.5 microg/mL, over a range from 2.5 to 250 microg/mL. The coefficients of variation did not exceed 3.9% and the mean measured concentrations did not deviate more than 8% from the target for both intra- and interassay precision and accuracy. Plasma GHB was found to be stable at -20 degrees C for up to 9 months, at room temperature for 48 h, and after 3 freeze/thaw cycles. It was also found to be stable in processed samples stored at room temperature for 5 days and for 15 days at -20 degrees C. PMID:14606997

Chen, Meng; Andrenyak, David M; Moody, David E; Foltz, Rodger L



Metabolism of gamma hydroxybutyrate in human hepatoma HepG2 cells by the aldo-keto reductase AKR1A1.  


Gamma hydroxybutyrate (GHB) is a recreational and date-rape drug, for which the detection following ingestion is hampered by rapid metabolism and its endogenous presence. GHB catabolism occurs mainly by its oxidation to succinic semialdehyde (SSA), which converts to succinate and enters the tricarboxylic acid cycle. A high Km aldehyde reductase has previously been reported to catalyse the NADP-dependent oxidation of GHB at high concentrations. It is assumed that this enzyme is identical to the aldo-keto reductase AKR1A1, but its role in GHB oxidation has not been fully evaluated. In this study, the extent of AKR1A1 in GHB metabolism has been determined in HepG2 cells using RNA-interference technology. The gene encoding AKR1A1 was targeted by siRNA. Results demonstrate a successful knock-down of the AKR1A1 gene with 92% reduction in total mRNA and 93% reduction in protein expression. Demolishing AKR1A1 expression in HepG2 cells leads to significant 82% decrease in NADP-dependent GHB-dehydrogenase activity at high concentration (10mM) of GHB. Moreover, when exposing the cells to 50?M of GHB for 24h, and measuring intracellular and extracellular GHB levels by GC/MS, a significant two-fold increase was observed on GHB intracellular level in silenced cells. In contrast, measuring SSA-reductase activity in silenced cells indicated that AKR1A1 is not involved in endogenous GHB production. These findings describe a pathway for GHB metabolism in the liver which should be useful in GHB exposure cases, and will enable a better understanding of the enzymes participating in its metabolism at natural and overexposed levels. PMID:25256836

Alzeer, Samar; Ellis, Elizabeth M



Phenylacetic acids and the structurally related non-steroidal anti-inflammatory drug diclofenac bind to specific gamma-hydroxybutyric acid sites in rat brain.  


Gamma-Hydroxybutyric acid (GHB) is a proposed neurotransmitter or neuromodulator with a yet unresolved mechanism of action. GHB binds to both specific high-affinity GHB binding sites and to gamma-aminobutyric acid subtype B (GABA(B)) receptors in the brain. To separate specific GHB effects from GABA(B) receptor effects, it is imperative to develop GHB selective and potent compounds. We generated the compound, 4-(biphen-4-yl)-4-hydroxybutyric acid, which is the 4-hydroxyl analogue of the non-steroidal anti-inflammatory drug (NSAID) fenbufen (referred to as gamma-hydroxyfenbufen). When measured in a rat brain homogenate [(3)H]NCS-382 binding assay, gamma-hydroxyfenbufen inhibited [(3)H]NCS-382 binding with a 10-fold higher affinity than GHB (K(i) 0.44 microM), thus establishing it as a novel lead structure. The active metabolite of fenbufen, 4-biphenylacetic acid inhibited [(3)H]NCS-382 binding with a twofold higher affinity than GHB. Measuring the affinities of structurally related NSAIDs for the [(3)H]NCS-382 site identified diclofenac, a clinically relevant NSAID (Voltaren, Diclon) of the phenylacetic acid (PAA) type, as a GHB ligand (K(i) value of 5.1 microM). Other non-NSAID PAAs also exhibited affinities similar to GHB. Our data raise the interesting possibility that the widely used over-the-counter drug compound, diclofenac, might affect GHB binding at relevant clinical dosages. Furthermore, the identification of PAAs as GHB ligands supplies new information about the structural preferences of the GHB ligand-binding site. PMID:19645815

Wellendorph, Petrine; Høg, Signe; Skonberg, Christian; Bräuner-Osborne, Hans



Quantitation of Gamma-Hydroxybutyric Acid in Dried Blood Spots: Feasibility Assessment for Newborn Screening of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency  

PubMed Central

Objective SSADH deficiency, the most prevalent autosomal recessive disorder of GABA degradation, is characterized by elevated gamma-hydroxybutyric acid (GHB). Neurological outcomes may be improved with early intervention and anticipatory guidance. Morbidity has been compounded by complications, e.g. hypotonia, in undiagnosed infants with otherwise routine childhood illnesses. We report pilot methodology on the feasibility of newborn screening for SSADH deficiency. Method Dried blood spot (DBS) cards from patients affected with SSADH deficiency were compared with 2831 archival DBS cards for gamma-hydroxybutyric acid content. Following extraction with methanol, GHB in DBS was separated and analyzed using ultra high-performance liquid chromatography tandem mass spectrometry. Results Methodology was validated to meet satisfactory accuracy and reproducibility criteria, including intra-day and inter-day validation. Archival refrigerated dried blood spots samples of babies, infants and children (N=2831) were screened for GHB, yielding a mean +/- S.D. of 8 ± 5 nM (99.9 %-tile 63 nM) (Min 0.0 Max 78 nM). The measured mean and median concentrations in blood spots derived from seven SSADH deficient patients were 1182 nM and 699 nM respectively (Min 124, Max 4851nM). Conclusions GHB concentration in all 2831 dried blood spot cards was well below the lowest concentration of affected children. These data provide proof-of-principle for screening methodology to detect SSADH deficiency with applicability to newborn screening and earlier diagnosis. PMID:23742746

Forni, Sabrina; Pearl, Phillip L.; Gibson, K. Michael; Yu, Yuezhou; Sweetman, Lawrence



Temporal differences in gamma-hydroxybutyrate overdoses involving injecting drug users versus recreational drug users in Helsinki: a retrospective study  

PubMed Central

Background Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have been profiled as 'party drugs' used mainly at dance parties and in nightclubs on weekend nights. The purpose of this study was to examine the frequency of injecting drug use among GHB/GBL overdose patients and whether there are temporal differences in the occurrence of GHB/GBL overdoses of injecting drug and recreational drug users. Methods In this retrospective study, the ambulance and hospital records of suspected GHB- and GBL overdose patients treated by the Helsinki Emergency Medical Service from January 1st 2006 to December 31st 2007 were reviewed. According to the temporal occurrence of the overdose, patients were divided in two groups. In group A, the overdose occurred on a Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. Group B consisted of overdoses occurring on outside this time frame. Results Group A consisted of 39 patient contacts and the remaining 61 patient contacts were in group B. There were statistically significant differences between the two groups in (group A vs. B, respectively): history of injecting drug abuse (33% vs. 59%, p = 0.012), reported polydrug and ethanol use (80% vs. 62%, p = 0.028), the location where the patients were encountered (private or public indoors or outdoors, 10%, 41%, 41% vs. 25%, 18%, 53%, p = 0.019) and how the knowledge of GHB/GBL use was obtained (reported by patient/bystanders or clinical suspicion, 72%, 28% vs. 85%, 10%, p = 0.023). Practically all (99%) patients were transported to emergency department after prehospital care. Conclusion There appears to be at least two distinct groups of GHB/GBL users. Injecting drug users represent the majority of GHB/GBL overdose patients outside weekend nights. PMID:22296777



Concurrent use of methamphetamine, MDMA, LSD, ketamine, GHB, and flunitrazepam among American youths  

Microsoft Academic Search

BackgroundThe magnitude and the characteristics of the use of methamphetamine, MDMA (Ecstasy), LSD (d-lysergic acid diethylamide), ketamine, GHB (gamma-hydroxybutyrate), and flunitrazepam (Rohypnol) were examined in a probability sample of the U.S. civilian population that included multiethnic urban, suburban, and rural youths aged 16–23 (N=19,084).

Li-Tzy Wu; William E. Schlenger; Deborah M. Galvin



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


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. PMID:25217550

Korb, Ann-Sophie; Cooper, Gail



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

PubMed Central

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:25024938

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



A qualitative analysis of GHB use among gay men: Reasons for use despite potential adverse outcomes  

PubMed Central

This paper examines the use of gamma-hydroxybutyrate (GHB) among a sample of gay men in New York City, who identify GHB as their most frequently used club drug. The sample was drawn from a larger longitudinal investigation of club drug using men. Thematic analysis yielded findings regarding perceived stigma for GHB use, tolerance of potential adverse side effects, and reasons for why some prefer this substance to other club drugs. Specifically, our findings suggest that GHB is viewed unfavorably in many social circles, that side effects are tolerated by frequent GHB users, and that the drug is chosen over other substances because the short duration of action, energy boost, sleep assistance, increase in libido, and limited after-effects. Examining the reasons why men use this substance will lead to the development of GHB specific prevention strategies, which accurately address the consequences of use as well as the motivations that individuals possess for using the substance. PMID:23543728

Palamar, Joseph J.; Halkitis, Perry N.



[Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions].  


After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages. PMID:9376042

Kleinschmidt, S; Bauer, M; Grundmann, U; Schneider, A; Wagner, B; Graeter, T



Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature.  


GHB, GBL, and 1,4-BD are prevalent drugs of abuse in the United States. Unfortunately, attempts to regulate GHB have been circumvented by clandestine trafficking through the Internet and marketing of "natural" chemical precursors . Despite repeated FDA warnings to the public about their dangers as well as recent federal scheduling of GHB and GBL, they remain accessible as "club drugs" on Internet websites, as natural dietary supplements in health food stores, and as illicit products manufactured at home or in clandestine laboratories. EDs and poison control centers nationwide will undoubtedly continue to manage GHB, GBL, and 1,4-BD toxicities. PMID:11138892

Shannon, M; Quang, L S



GHB acid: A rage or reprive  

PubMed Central

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

Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita



Testing for GHB in hair by GC/MS/MS after a single exposure. Application to document sexual assault.  


Gamma-hydroxybutyric acid, or GHB, is a substance naturally present within mammal species. Properties of neurotransmitter or neuromodulator are generally given to this substance. GHB is therapeutically used as an anesthetic, but can be used for criminal offenses (date-rape drug). It appears that the window of detection of GHB is very short in both blood and urine, and therefore its presence is very difficult to prove after a rape case. In order to document single exposure, we investigated the use of hair. Hair was collected one month after the allegated event in order to sample the corresponding period after regular growing. After rapid (2 min) decontamination with dichloromethane, the hair shaft was cut into 3-mm segments. They were overnight incubated in 0.01 N NaOH in the presence of GHB-d6, followed by neutralization and extraction in ethyl acetate under acidic conditions. GHB (precursor ion m/z 233, product ions m/z 147 and 148) was tested by GC/MS/MS (Finnigan TSQ 700) after derivatization with BSTFA + 1% TMCS. Physiological concentrations (n = 24) were in the range 0.5 to 12.0 ng/mg, with no influence due to hair color. No variation of concentrations was observed along the hair shaft in controlled subjects, except for the proximal segment, due to an incorporation through sweat. This demonstrates that endogenous levels for each single subject are constant during hair growth. A controlled human administration of 25 mg/kg to a volunteer demonstrated that a single exposure to GHB is detectable in hair after segmentation. In a case of rape under influence, a clear increase of the corresponding segment (about 2.4 ng/mg) in time was observed, in comparison with the other segments (0.6 to 0.8 ng/mg). This study demonstrates that a single exposure to GHB in a case of sexual assault can be documented by hair analysis when collected about one month after the crime. PMID:12570228

Kintz, Pascal; Cirimele, Vincent; Jamey, Carole; Ludes, Bertrand



Unusually high concentrations in a fatal GHB case.  


The first case in France involving a fatal overdose resulting from the ingestion of gamma-hydroxybutyrate (GHB) is presented. GHB was tested by gas chromatography-mass spectrometry (GC-MS) after precipitation. Briefly, 20 microL of body fluids (blood, bile, urine, gastric contents, or vitreous humor) was pipetted in a glass tube, followed by 20 microL GHB-d6 and 45 microL acetonitrile. After vortex mixing and centrifuging, the supernatant was collected and evaporated to dryness. The residue was derivatized with BSTFA with 1% TMCS for 20 min at 70 degrees C. After injection on a 30-m HP5 MS capillary column, GHB (m/z 233, 204, and 147) and GHB-d6 (m/z 239) were identified by MS. GHB was also tested in pubic hair after incubation in 0.01 N NaOH, neutralization, acidification, extraction in ethyl acetate and derivatization with MTBSTFA, using GC-MS-MS. GHB was positive in all the tested specimens, with the following concentrations 2937, 33,727, 1800, and 2856 mg/L in femoral blood, urine, bile, and vitreous humor, respectively. This seems to be the highest blood concentration ever observed. Postmortem redistribution appears weak, as the concentration in cardiac blood was 3385 mg/L (cardiac blood/femoral blood ratio of 1.15). Oral route was suggested with GHB at 7.08 g in 100 mL of gastric contents. Pubic hair analysis clearly indicated chronic GHB abuse, with concentrations along the shaft in the range 19.4 to 25.0 ng/mg (in comparison with physiological concentrations < 2 ng/mg). Methylenedioxymethamphetamine was present in femoral blood at 144 ng/mL. These results are consistent with an acute fatal overdose of GHB. PMID:16168184

Kintz, Pascal; Villain, Marion; Pélissier, Anne-Laure; Cirimele, Vincent; Leonetti, Georges



What constitutes a normal ante-mortem urine GHB concentration?  


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. PMID:19239966

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



A comprehensive review of MDMA and GHB: two common club drugs.  


"Club drugs" have become alarmingly popular. The use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and gamma-hydroxybutyrate (GHB), in particular, has increased dramatically from 1997-1999. The pharmacokinetics of MDMA and GHB appear to be nonlinear, making it difficult to estimate a dose-response relationship. The drug MDMA is an amphetamine analog with sympathomimetic properties, whereas GHB is a gamma-aminobutyric acid analog with sedative properties. Symptoms of an MDMA toxic reaction include tachycardia, sweating, and hyperthermia. Occasional severe sequelae include disseminated intravascular coagulation, rhabdomyolysis, and acute renal failure. Treatment includes lowering the body temperature and maintaining adequate hydration. Symptoms of GHB intoxication include coma, respiratory depression, unusual movements, confusion, amnesia, and vomiting. Treatment includes cardiac and respiratory support. Because of the popularity of these agents and their potentially dangerous effects, health care professionals must be familiar with these substances and the treatment options for patients who present with symptoms of a toxic reaction. PMID:11765302

Teter, C J; Guthrie, S K



Rapid and direct analysis of gamma-hydroxybutyric acid in urine by capillary electrophoresis-electrospray ionization ion-trap mass spectrometry.  


The present work was aimed at the development of a capillary electrophoretic analysis of gamma-hydroxybutyric acid (GHB) using electrospray ion trap mass spectrometry to achieve the direct and unequivocal detection of this analyte in human urine. Optimized capillary electrophoretic conditions were: injection, 20 s at 0.5 psi (1 psi = 6894.76 Pa); buffer electrolyte, 12.5 mM ammonium formate adjusted to pH 8.35 with diethylamine; fused silicacapillary: 100 cm x 50 microm i.d.; separation voltage, 25 kV (forward polarity) + 0.5 psi; room temperature. Electrospray and mass spectrometric conditions were: drying gas and nebulizing gas (nitrogen) at flow rate 3 l/min, temperature 250 degrees C, nebulizer pressure: 10 psi; sheath liquid solution: methanol-water (90:10) containing 0.1% ammonia delivered at 3 microl/min; spray voltage 3.5 kV. Mass spetrometric detection was carried out in the selected ion monitoring mode of negative molecular ions at 103 m/z for GHB and 115 m/z for maleic acid (I.S.). Under these conditions the baseline separation of GHB and the I.S. was obtained. The selectivity of the analysis allowed for direct injection of unextracted urine, previously diluted 1:4 with water. Linearity was assessed in the GHB concentration range from 80 to 1280 microg/ml in urine. Analytical sensitivity (as limit of detection) resulted about 5 microg/ml in water and 20 microg/ml in original urine. Analytical precision was fairly acceptable with R.S.D. values lower than 5% for migration times and 18% for quantitation in real samples, in both intra day and day-to-day experiments. On these grounds, the developed method can be adopted for rapid identification of acute intoxications from GHB in humans. PMID:15532575

Gottardo, Rossella; Bortolotti, Federica; Trettene, Maristella; De Paoli, Giorgia; Tagliaro, Franco



Comparative abuse liability of GHB and ethanol in humans  

PubMed Central

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

Johnson, Matthew W.; Griffiths, Roland R.



Differentiating the discriminative stimulus effects of gamma-hydroxybutyrate and ethanol in a three-choice drug discrimination procedure in rats.  


Anecdotal reports indicate that GHB produces subjective effects similar to those of ethanol. However, recent investigations comparing the discriminative stimulus effects of GHB to those of ethanol suggest that the subjective effects of these substances may differ considerably. To explore further potential differences between GHB and ethanol, 16 male Sprague-Dawley rats were trained in a three-lever drug discrimination procedure to discriminate ethanol (1.0 g/kg, experiment 1; 1.5 g/kg, experiment 2) and GHB (300 mg/kg) from vehicle. Dose-response functions determined with both training compounds revealed a clear dissociation between the discriminative stimulus effects of these drugs. As expected, the GHB precursors gamma-butyrolactone and 1,4-butanediol produced full substitution for GHB. In addition, the GABA(B) receptor agonist baclofen substituted for GHB, whereas the benzodiazepine flunitrazepam and the NMDA receptor antagonist ketamine engendered greater responding on the ethanol-lever. GHB's discriminative stimulus effects were blocked by the GABA(B) receptor antagonist CGP-35348 but only partially blocked by the putative GHB receptor antagonist NCS 382. These findings are consistent with previous reports of GHB's discriminative stimulus effects in two-choice drug discrimination procedures and provide additional evidence that these effects are distinct from those of ethanol. PMID:18374971

Baker, Lisa E; Searcy, Gabriel D; Pynnonen, Dori M; Poling, Alan



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


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. PMID:22884787

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



Determination of gamma-hydroxybutyric acid in dried blood spots using a simple GC-MS method with direct "on spot" derivatization.  


The objective of this study was the development of an accurate and sensitive method for the determination of gamma-hydroxybutyric acid (GHB) in dried whole blood samples using a GC-MS method. The complete procedure was optimized, with special attention on the sample pretreatment, and validated. Therefore, dried blood spots of only 50 ?l were prepared and, after the addition of internal standard GHB-d6, directly derivatized using 100 ?l of a freshly prepared mixture of trifluoroacetic acid anhydride and heptafluorobutanol (2:1). The derivatized extract was injected into a gas chromatograph coupled to a mass spectrometer (GC-MS), operating in the electron impact mode, with a total run time of 12.3 min. Method validation included the evaluation of linearity, precision, accuracy, sensitivity, selectivity, and stability. A weighting factor of 1/x(2) was chosen and acceptable intra-batch precision, inter-batch precision, and accuracy were seen. The linear calibration curve ranged from 2 to 100 ?g/ml, with a limit of detection of 1 ?g/ml. Our procedure, utilizing the novel approach of direct "on spot" derivatization followed by analysis with GC-MS, proved to be reliable, fast, and applicable in routine toxicology. PMID:20835862

Ingels, Ann-Sofie M E; Lambert, Willy E; Stove, Christophe P



Gamma-hydroxybutyric acid endogenous production and post-mortem behaviour - the importance of different biological matrices, cut-off reference values, sample collection and storage conditions.  


Gamma-Hydroxybutyric Acid (GHB) is an endogenous compound with a story of clinical use, since the 1960's. However, due to its secondary effects, it has become a controlled substance, entering the illicit market for recreational and "dance club scene" use, muscle enhancement purposes and drug-facilitated sexual assaults. Its endogenous context can bring some difficulties when interpreting, in a forensic context, the analytical values achieved in biological samples. This manuscript reviewed several crucial aspects related to GHB forensic toxicology evaluation, such as its post-mortem behaviour in biological samples; endogenous production values, whether in in vivo and in post-mortem samples; sampling and storage conditions (including stability tests); and cut-off reference values evaluation for different biological samples, such as whole blood, plasma, serum, urine, saliva, bile, vitreous humour and hair. This revision highlights the need of specific sampling care, storage conditions, and cut-off reference values interpretation in different biological samples, essential for proper practical application in forensic toxicology. PMID:25287794

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



Determination of ?-hydroxybutyrate (GHB), ?-hydroxybutyrate (BHB), pregabalin, 1,4-butane-diol (1,4BD) and ?-butyrolactone (GBL) in whole blood and urine samples by UPLC-MSMS.  


The demand of high throughput methods for the determination of gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butane-diol (1,4BD) as well as for pregabalin is increasing. Here we present two analytical methods using ultra-high pressure liquid chromatography (UPLC) and tandem mass spectrometric (MS/MS) detection for the determination of GHB, beta-hydroxybutyrate (BHB), pregabalin, 1,4BD and GBL in whole blood and urine. Using the 96-well formate, the whole blood method is a simple high-throughput method suitable for screening of large sample amounts. With an easy sample preparation for urine including only dilution and filtration of the sample, the method is suitable for fast screening of urine samples. Both methods showed acceptable linearity, acceptable limits of detection, and limits of quantification. The within-day and between-day precisions of all analytes were lower than 10% RSD. The analytes were extracted from matrices with recoveries near 100%, and no major matrix effects were observed. Both methods have been used as routine screening analyses of whole blood and urine samples since January 2010. PMID:22226469

Dahl, Sandra Rinne; Olsen, Kirsten Midtbøen; Strand, Dag Helge



An Improved Method for the Analysis of GHB in Human Hair by Liquid Chromatography Tandem Mass Spectrometry†  


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. PMID:25433016

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



Acute toxicity and withdrawal syndromes related to ?-hydroxybutyrate (GHB) and its analogues ?-butyrolactone (GBL) and 1,4-butanediol (1,4-BD).  


Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues gamma-butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues. PMID:21548140

Wood, David M; Brailsford, Alan D; Dargan, Paul I



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

ERIC Educational Resources Information Center

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,…

Henck, Colin; Nally, Luke



Screening and confirmation methods for GHB determination in biological fluids.  


The purpose of this review is to provide a comprehensive overview of reported methods for screening and confirmation of the low-molecular-weight compound and drug of abuse gamma-hydroxybutyric acid (GHB) in biological fluids. The polarity of the compound, its endogenous presence, its rapid metabolism after ingestion, and its instability during storage (de novo formation and interconversion between GHB and its lactone form gamma-butyrolactone) are challenges for the analyst and for interpretation of a positive result. First, possible screening procedures for GHB are discussed, including colorimetric, enzymatic, and chromatography-based procedures. Confirmation methods for clinical and forensic cases mostly involve gas chromatography (coupled to mass spectrometry), although liquid chromatography and capillary zone electrophoresis have also been used. Before injection, sample-preparation techniques include (a combination of) liquid-liquid, solid-phase, or headspace extraction, and chemical modification of the polar compound. Also simple "dilute-and-shoot" may be sufficient for urine or serum. Advantages, limitations, and trends are discussed. PMID:24500753

Ingels, Ann-Sofie M E; Wille, Sarah M R; Samyn, Nele; Lambert, Willy E; Stove, Christophe P



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


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. PMID:15516306

Couper, Fiona J; Logan, Barry K



Baclofen and ?-Hydroxybutyrate (GHB), a Dangerous Combination.  


Baclofen is a ?-aminobutyric acid (GABA)-? receptor agonist with a muscle relaxant effect. It increases GABA activity and reduces the production of glutamate and dopamine. The GABA precursor ?-hydroxybutyrate (GHB) has gained popularity as a drug of abuse. For the first time, we report a case of a GHB-dependent patient, who ingested several days' doses of baclofen (80 mg) simultaneously with 0.3 L (215 g) of illicit GHB. Baclofen (40 mg/d) was prescribed to prevent relapse after a successful detoxification. The patient developed a rapid coma (E2M5V1 with oxygen support), bradypnea, and hypotonia. Physicians should be alert to the danger of this combination because of the hazards of coma and respiratory distress. PMID:25494007

Kamal, Rama M; Qurishi, Rouhollah; De Jong, Cornelis A J



Utilisation de l'acide gamma-hydroxybutyrique (ghb) dans les rave-parties et pour la soumission chimique en france : mythe ou réalité?  


Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in rave-parties and for bodybuilders. It seems to be a controversy between media coverage and the results of toxicological analysis done in high-level laboratories. In order to clarify this problem, we compiled the data of 6 laboratories. They used the same analytical method by GC/MS. Depending the laboratory, the limit of detection was 1-2 ?g/mL and the limit of quantification was 2.5-5 ?g/ mL. Two labs where looking for GHB in each forensic case (100 and 150 cases a year). Others labs performed GHB analysis only on specific request (each 10 cases a year). Mean time between ingestion of GHB and blood/urine sampling was 12-48 h. Mean time between sampling and analysis was much higher (a few hours to a few month. All samples were stored at +4°C. Only 3 cases were considered as positive (blood GHB : 165, 132 and 114 ?g/mL, urine GHB : 7450 and 436 ?g/ mL) They were admitted in an hospital EU. Interpreting results remains very difficult because GHB is endogenous, present in blood and urine, and its half-life is very short. One has to report only « positive » GHB results when amounts are higher than 5 ?g/mL in blood and 10 ?g/mL in urine. Obviously, forensic toxicologists have to play a very important part in diagnosis of GHB intoxications and estimating its frequency. Actually, because the lack of data in France, it is not possible to answer the question asked in the title of this paper. PMID:24862523

Deveaux, M; Renet, S; Renet, V; Gaulier, Jm; Kintz, P; Verstraete, A; Gosset, D



Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins.  

PubMed Central

The aldo-keto reductase (AKR) 7 family is composed of the dimeric aflatoxin B(1) aldehyde reductase (AFAR) isoenzymes. In the rat, two AFAR subunits exist, designated rAFAR1 and rAFAR2. Herein, we report the molecular cloning of rAFAR2, showing that it shares 76% sequence identity with rAFAR1. By contrast with rAFAR1, which comprises 327 amino acids, rAFAR2 contains 367 amino acids. The 40 extra residues in rAFAR2 are located at the N-terminus of the polypeptide as an Arg-rich domain that may form an amphipathic alpha-helical structure. Protein purification and Western blotting have shown that the two AFAR subunits are found in rat liver extracts as both homodimers and as a heterodimer. Reductase activity in rat liver towards 2-carboxybenzaldehyde (CBA) was resolved by anion-exchange chromatography into three peaks containing rAFAR1-1, rAFAR1-2 and rAFAR2-2 dimers. These isoenzymes are functionally distinct; with NADPH as cofactor, rAFAR1-1 has a low K(m) and high activity with CBA, whereas rAFAR2-2 exhibits a low K(m) and high activity towards succinic semialdehyde. These data suggest that rAFAR1-1 is a detoxication enzyme, while rAFAR2-2 serves to synthesize the endogenous neuromodulator gamma-hydroxybutyrate (GHB). Subcellular fractionation of liver extracts showed that rAFAR1-1 was recovered in the cytosol whereas rAFAR2-2 was associated with the Golgi apparatus. The distinct subcellular localization of the rAFAR1 and rAFAR2 subunits was confirmed by immunocytochemistry in H4IIE cells. Association of rAFAR2-2 with the Golgi apparatus presumably facilitates secretion of GHB, and the novel N-terminal domain may either determine the targeting of the enzyme to the Golgi or regulate the secretory process. A murine AKR protein of 367 residues has been identified in expressed sequence tag databases that shares 91% sequence identity with rAFAR2 and contains the Arg-rich extended N-terminus of 40 amino acids. Further bioinformatic evidence is presented that full-length human AKR7A2 is composed of 359 amino acids and also possesses an additional N-terminal domain. On the basis of these observations, we conclude that AKR7 proteins can be divided into two subfamilies, one of which is a Golgi-associated GHB synthase with a unique, previously unrecognized, N-terminal domain that is absent from other AKR proteins. PMID:12071861

Kelly, Vincent P; Sherratt, Philip J; Crouch, Dorothy H; Hayes, John D



Management of Gamma-Butyrolactone Dependence with Assisted Self-Administration of GBL  

PubMed Central

Gamma-hydroxybutyric acid (GHB) and its liquid precursor gamma-butyrolactone (GBL) have become increasingly popular beyond the clubbing culture resulting in daily consumption and dependence in the broader population. This case report illustrates the challenges of managing GHB-withdrawal and a possibly superior future approach of its management by titration and tapering of the addictive agent. PMID:25054071

Meyer, Rafael; Jenewein, Josef



Management of Gamma-Butyrolactone Dependence with Assisted Self-Administration of GBL.  


Gamma-hydroxybutyric acid (GHB) and its liquid precursor gamma-butyrolactone (GBL) have become increasingly popular beyond the clubbing culture resulting in daily consumption and dependence in the broader population. This case report illustrates the challenges of managing GHB-withdrawal and a possibly superior future approach of its management by titration and tapering of the addictive agent. PMID:25054071

Meyer, Rafael; Jenewein, Josef; Boettger, Soenke



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


?-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 ?-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. PMID:25088910

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



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.  


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. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24947196

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



Behavioral Analyses of GHB: Receptor Mechanisms  

PubMed Central

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

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



Physical dependence on gamma-hydroxybutrate (GHB) prodrug 1,4-butanediol (1,4-BD): Time course and severity of withdrawal in baboons  

PubMed Central

Background 1,4-butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) pro-drug, with multiple commercial uses, and a drug of abuse. Although there are case reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated the physical dependence potential of 1,4-BD and characterized the time course of withdrawal. Methods Vehicle and then 1,4-BD were administered continuously 24 h/day via intragastric catheters in male baboons (Papio anubis, n=3). Dosing was initiated at 100 mg/kg and increased by 100 mg/kg/day to 400 mg/kg. After a stabilization period, doses of 500 and then 600 mg/kg/day were each maintained for 3-4 weeks. Plasma levels of 1,4-BD and GHB were determined for each dose condition. Physical dependence was assessed via administration of a GABA-B antagonist (precipitated withdrawal test) during administration of the 600 mg/kg dose and via abrupt termination of chronic 1,4-BD administration (spontaneous withdrawal test). Outcome measures included the number of food pellets earned, performance on a fine-motor task, observed behaviors, and plasma levels of GHB and 1,4-BD. Results Following maintenance of 1,4-BD 600 mg/kg for 3 weeks, the number of food pellets earned was significantly decreased. At the end of chronic 1,4-BD dosing, the levels of GHB in plasma ranged from 1290- 2300 ?mol/L and levels of 1,4-BD in plasma ranged from 13.1 -37.9 ?mol/L. Signs of physical dependence were observed following precipitated and spontaneous withdrawal tests. Seizures were not observed. Conclusions These data indicate chronic 1,4-BD produced physical dependence in baboons and the withdrawal syndrome can be characterized as mild to intermediate. PMID:23538206

Goodwin, Amy K.; Gibson, K. Michael; Weerts, Elise M.



Determination of gamma-hydroxybutyric acid in serum and urine by headspace solid-phase dynamic extraction combined with gas chromatography-positive chemical ionization mass spectrometry.  


Gamma-hydroxybutyric acid is an emerging drug of abuse. Beside relaxation and euphoria it causes hypnosis and unconsciousness. Therefore the substance is misused as recreational drug and at drug-facilitated sexual assaults. An automated and effortless method for quantitation of gamma-hydroxybutyric acid in serum and urine was optimized and validated. Five hundred microliters sample volume are used for both matrices. The acid catalyzed conversion of gamma-hydroxybutyric acid to the corresponding gamma-butyrolactone is applied. Furthermore the method is based on headspace solid-phase dynamic extraction coupled with gas chromatography-mass spectrometry. The extraction process is performed by repeated aspiration and ejection of the headspace through a steel cannula which is coated on the inside with a polydimethylsiloxane sorbent. Thus absorption of analyte molecules by the sorbent is achieved. The influence of parameters as sorbent type, incubation temperature, number of extraction strokes, injection port temperature and injection flow speed on extraction recovery was investigated. The validation revealed good accuracy with a bias less than +/-5%. Intra- and interday precision determined at 10, 50 and 150 microg/ml for each matrix were in following ranges: 1.96-3.49% (intraday, serum), 2.38-4.31% (intraday, urine), 2.33-5.13% (interday, serum) and 2.53-5.64% (interday, urine). The method provided good linearity between 2 and 200 microg/ml yielding coefficients of determination R(2) > or = 0.9985. Limit of detection were determined at 0.16 microg/ml for serum and 0.17 microg/ml for urine, respectively. This method exhibits a fast, solvent-free and widely automated extraction process. It has been applied to toxicological routine analysis and therapeutic drug monitoring successfully. PMID:19327780

Lenz, Daniel; Kröner, Lars; Rothschild, Markus A



Identifying Drugs  


... Molly) GHB - Gamma-Hydroxybutyric Acid Heroin Hydromorphone Inhalants Ketamine Khat LSD Marijuana Methadone Methamphetamine Morphine Opium Oxycodone ... Molly) GHB - Gamma-Hydroxybutyric Acid Heroin Hydromorphone Inhalants Ketamine Khat LSD Marijuana Methadone Methamphetamine Morphine Opium Oxycodone ...


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

Federal Register 2010, 2011, 2012, 2013

...Administration (DEA) to be 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) in bulk active...



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

Federal Register 2010, 2011, 2012, 2013

...registered as a bulk manufacturer of Gamma Hydroxybutyric Acid (GHB) (2010), a basic class of controlled substance listed in...The company plans to manufacture Gamma Hydroxybutyric Acid (GHB) [[Page 17969



Club Drugs (GHB, Ketamine, and Rohypnol)  


... group. GHB (Xyrem) is a central nervous system (CNS) depressant that was approved by the Food and Drug Administration (FDA) in 2002 for use in the treatment of narcolepsy (a sleep disorder). This approval came with severe restrictions, including its ...


Differential effects of GABAB receptor subtypes, {gamma}-hydroxybutyric Acid, and Baclofen on EEG activity and sleep regulation.  


The role of GABA(B) receptors in sleep is still poorly understood. GHB (?-hydroxybutyric acid) targets these receptors and is the only drug approved to treat the sleep disorder narcolepsy. GABA(B) receptors are obligate dimers comprised of the GABA(B2) subunit and either one of the two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b). To better understand the role of GABA(B) receptors in sleep regulation, we performed electroencephalogram (EEG) recordings in mice devoid of functional GABA(B) receptors (1(-/-) and 2(-/-)) or lacking one of the subunit 1 isoforms (1a(-/-) and 1b(-/-)). The distribution of sleep over the day was profoundly altered in 1(-/-) and 2(-/-) mice, suggesting a role for GABA(B) receptors in the circadian organization of sleep. Several other sleep and EEG phenotypes pointed to a more prominent role for GABA(B1a) compared with the GABA(B1b) isoform. Moreover, we found that GABA(B1a) protects against the spontaneous seizure activity observed in 1(-/-) and 2(-/-) mice. We also evaluated the effects of the GHB-prodrug GBL (?-butyrolactone) and of baclofen (BAC), a high-affinity GABA(B) receptor agonist. Both drugs induced a state distinct from physiological sleep that was not observed in 1(-/-) and 2(-/-) mice. Subsequent sleep was not affected by GBL whereas BAC was followed by a delayed hypersomnia even in 1(-/-) and 2(-/-) mice. The differential effects of GBL and BAC might be attributed to differences in GABA(B)-receptor affinity. These results also indicate that all GBL effects are mediated through GABA(B) receptors, although these receptors do not seem to be involved in mediating the BAC-induced hypersomnia. PMID:20962240

Vienne, Julie; Bettler, Bernhard; Franken, Paul; Tafti, Mehdi



Analysis of gamma-hydroxybutyric acid, DL-lactic acid, glycolic acid, ethylene glycol and other glycols in body fluids by a direct injection gas chromatography-mass spectrometry assay for wide use.  


Analysis of blood of severely intoxicated patients always requires prompt investigation. Diagnosis of intoxication with ethylene glycol, gamma-hydroxybutyric acid or D-lactic acid takes hours, since several different procedures are required. Rapid derivatization of the common hydroxyl function may resolve this analytical problem. Here we describe a fast method for the simultaneous measurement of ethylene glycol, glycolic acid, gamma-hydroxybutyric acid and racemic lactic acid. Only 20 microl of serum, plasma or urine are required for immediate derivatization at 70 degrees C with 750 microl of bis-N,O-trimethylsilyl trifluoroacetamide after adding 20 microl of internal standard solution (1,3-propylene glycol) and 20 microl of the catalyst dimethylformamide. After centrifugation an aliquot is transferred to a gas chromatographic system and analyzed with electron-impact mass spectrometry in selective ion monitoring mode. The derivatized acids and ethylene glycol are well separated and detected with a limit of detection ranging from 0.12 mg/l for ethylene glycol to 0.95 mg/l for gamma-hydroxybutyric acid, while the limit of quantification ranged from 0.4 mg/l for ethylene glycol to 3.15 mg/l for gamma-hydroxybutyric acid. The method is linear from 0.5 to 1800 mg/l blood for ethylene glycol, from 0.7 to 1200 mg/l for lactic acid, from 1.2 to 1800 mg/l for glycolic acid, and from 3.2 to 200 mg/l for gamma-hydroxybutyric acid, with analytical recoveries, accuracy, day-to-day and within-day precision well within the required limits. Total analysis time with one calibrator was 30 min, derivatization time included. This method is very suitable for emergency toxicology, since several toxic substances can be quantified simultaneously in a fast and sensitive manner. PMID:15576294

Van Hee, Paul; Neels, Hugo; De Doncker, Mireille; Vrydags, Nicolas; Schatteman, Katinka; Uyttenbroeck, Wim; Hamers, Nicole; Himpe, Dirk; Lambert, Willy



Reconstructors: Nothing To Rave About - Episode 2. Students learn about gas chromatography/mass spectrometry, gamma hydroxybutyrate (GHB), methylenedioxymethamphetamine and how ecstasy and other club drugs act on the nervous system  

NSDL National Science Digital Library

In Nothing To Rave About Episode 2, students are asked to uncover why there has been a dramatic increase in the number of teens admitted to the emergency room after partying at a local dance club. During their investigation, they learn how ecstasy and other club drugs act on the nervous system. Also available in Spanish.

Center for Technology in Teaching and Learning



?-Hydroxybutyrate (GHB)-Induced Respiratory Depression: Combined Receptor-Transporter Inhibition Therapy for Treatment in GHB Overdose  

PubMed Central

Overdose of ?-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 GABAB receptor antagonist, (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), and a specific GABAA 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 GABAB 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 GABAB and MCT inhibitors, alone and in combination, represent potential treatment options for GHB-induced respiratory depression. PMID:22561075

Morse, Bridget L.; Vijay, Nisha



Determination of gamma-hydroxybutyric acid in biofluids using a one-step procedure with "in-vial" derivatization and headspace-trap gas chromatography-mass spectrometry.  


A headspace-trap gas chromatography-mass spectrometry (HS-trap GC-MS) method was developed to determine GHB, a low molecular weight compound and drug of abuse, in various biological fluids. Combining this relatively novel and fully automated headspace technique with "in-vial" methylation of GHB allowed for a straightforward approach. One single method could be used for all biofluids (urine, plasma, serum, whole blood or lyzed blood), requiring only 100?l of sample. Moreover, our approach involves mere addition of all reagents and sample into one vial. Following optimization of headspace conditions and trap settings, validation was performed. Although sample preparation only consists of the addition of salt and derivatization reagents directly to a 100?l-sample in a HS-vial, adequate method sensitivity and selectivity was obtained. Calibration curves ranged from 5 to 150?g/ml GHB for urine, from 2 to 150?g/ml for plasma, and from 3.5 to 200?g/ml for whole blood. Acceptable precision and accuracy (<13% bias and imprecision) were seen for all quality controls (QC's) (LLOQ-level, low, medium, high), including for the supplementary serum- and lyzed blood-based QC's, using calibration curves prepared in plasma or whole blood, respectively. Incurred sample reanalysis demonstrated assay reproducibility, while cross-validation with another GC-MS method demonstrated that our method is a valuable alternative for GHB determination in toxicological samples, with the advantage of requiring only 100?l and minimal hands-on time, as sample preparation is easy and injection automated. PMID:23664352

Ingels, Ann-Sofie M E; Neels, Hugo; Lambert, Willy E; Stove, Christophe P



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


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. PMID:19288974

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



Development of a fluorescent sensor for illicit date rape drug GHB.  


The first fluorescent sensor (GHB Orange) for date rape drug GHB was developed. It exhibits the fluorescence quenching property for GHB and allows its detection in various drinks. The interaction mechanism was elucidated as intramolecular charge transfer induced by a hydrogen bond. This discovery will help in solving the drug facilitated sexual assault problems. PMID:24492471

Zhai, Duanting; Tan, Yong Qiao Elton; Xu, Wang; Chang, Young-Tae



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


In the Netherlands, ?-hydroxybutyric acid (GHB) was recently banned, but ?-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. PMID:25204614

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



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


?-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. PMID:24269284

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



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


?-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 (0.1-1?g/ml). The limit of detection and the limit of quantification of (2)H6-GHB were 0.05 and 0.1?g/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 1.8?g/ml and from 4.5 to 530?g/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 smoking, alcohol drinking, or caffeine-containing beverage drinking. PMID:24929871

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



?4?? GABAA receptors are high-affinity targets for ?-hydroxybutyric acid (GHB)  

PubMed Central

?-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 GABAA receptor subunits as possible candidates. A subsequent functional screening of various recombinant GABAA receptors in Xenopus laevis oocytes using the two-electrode voltage clamp technique showed GHB to be a partial agonist at ???- but not ???-receptors, proving that the ?-subunit is essential for potency and efficacy. GHB showed preference for ?4 over ?(1,2,6)-subunits and preferably activated ?4?1? (EC50 = 140 nM) over ?4?(2/3)? (EC50 = 8.41/1.03 mM). Introduction of a mutation, ?4F71L, in ?4?1(?)-receptors completely abolished GHB but not GABA function, indicating nonidentical binding sites. Radioligand binding studies using the specific GHB radioligand [3H](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 ?4 KO brain tissue compared with WT controls, corroborating the direct involvement of the ?4-subunit in high-affinity GHB binding. Our data link specific GHB forebrain binding sites with ?4-containing GABAA receptors and postulate a role for extrasynaptic ?4?-containing GABAA 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. PMID:22753476

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



?4?? GABA(A) receptors are high-affinity targets for ?-hydroxybutyric acid (GHB).  


?-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 ???- but not ???-receptors, proving that the ?-subunit is essential for potency and efficacy. GHB showed preference for ?4 over ?(1,2,6)-subunits and preferably activated ?4?1? (EC(50) = 140 nM) over ?4?(2/3)? (EC(50) = 8.41/1.03 mM). Introduction of a mutation, ?4F71L, in ?4?1(?)-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 ?4 KO brain tissue compared with WT controls, corroborating the direct involvement of the ?4-subunit in high-affinity GHB binding. Our data link specific GHB forebrain binding sites with ?4-containing GABA(A) receptors and postulate a role for extrasynaptic ?4?-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. PMID:22753476

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



Verve and Jolt: deadly new Internet drugs.  


As regulatory agencies have increased restrictions on the sale and marketing of gamma-hydroxybutyrate (GHB), they have been frustrated by the appearance of precursor molecules such as gamma-butyrolactone (GBL) that have become widely available over the Internet. These dangerous precursors are vigorously marketed to adolescents and young adults as dietary supplements that increase muscle mass and enhance sexual performance with seductive names such as Verve and Jolt, both easily recognizable teen icons. We present the case of an adolescent who ingested both of these GBL products 2 weeks apart, resulting in life-threatening respiratory depression and emergent intubation on both occasions. The GBL toxidrome, necessary acute interventions, and public health implications are reviewed. We urge all health care providers to report similar cases immediately to the FDA MedWatch system. Gamma-butyrolactone, gamma-hydroxybutyrate, respiratory insufficiency, central nervous system depressants, substance abuse. PMID:11015528

Winickoff, J P; Houck, C S; Rothman, E L; Bauchner, H



Uptake of gamma-valerolactone--detection of gamma-hydroxyvaleric acid in human urine samples.  


Gamma-valerolactone (GVL) is reported to be a substance that can be used as a legal substitute for gamma-hydroxybutyric acid (GHB), which is currently a controlled substance in several countries. Unlike gamma-butyrolactone and 1,4-butanediol, GVL is not metabolized to GHB, which causes the effects after uptake of these two chemicals. In the case of GVL, the lactone ring is split to gamma-hydroxyvaleric acid (GHV or 4-methyl-GHB) by a lactonase. Because of its affinity for the GHB receptor, GHV reveals similar effects to GHB, although it is less potent. Intoxications with GVL, or its use as a date rape drug, are conceivable. Despite these facts, there are no publications in the literature regarding detections of GHV in human samples. This study reports three cases, including five urine samples, in which GHV could be detected in concentrations between 3 and 5.8 mg/L. In one of these cases, a drug-facilitated sexual assault (DFSA) was assumed; four of these samples were from two people suspected of abusing GHB. The results indicate that GVL is used as an alternative to GHB and its precursors and should be taken seriously. GVL or GHV should be included in toxicological analysis, particularly in DFSA cases. More information is needed regarding the pharmacokinetics of GVL/GHV for the meaningful interpretation of positive or negative results. PMID:23486087

Andresen-Streichert, H; Jungen, H; Gehl, A; Müller, A; Iwersen-Bergmann, S



Gammahydroxybutyrate: an emerging drug of abuse that causes physical dependence  

Microsoft Academic Search

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects.




Near-fatal persistent anion- and osmolal-gap acidosis due to massive gamma-butyrolactone/ethanol intoxication.  


We report a case of an ethanol and massive gamma-butyrolactone (GBL) intoxication, the precursor of the recreational drug gamma-hydroxybutyric acid (GHB), resulting in life-threatening metabolic acidosis (pH 6.5) with a highly increased anion- and osmolal gap. Rapid analysis using gas chromatography revealed a GHB plasma concentration of 4400?mg/L, far above the upper limit concentration of 1000?mg/L found in adult fatalities attributed to GBL. Full recovery was established following supportive treatment including haemodialysis. This is the first report of a combined ethanol/GBL intoxication as a cause of high serum anion- and osmolal-gap metabolic acidosis. PMID:25205856

Heytens, Luc; Neels, Hugo; Van Regenmortel, Niels; van den Brink, Wim; Henckes, Manu; Schouwers, Sofie; Dockx, Greet; Crunelle, Cleo L



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?  


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 to determine a concentration of GHB of 14 ng/mg, in a 2-cm long segment (black hair). A case of rape under the influence of GHB was documented through hair analysis (black hair) and positive analysis of the glass she used. Sampled 7 days after the sexual assault, the three last 3-mm long proximal segments tested for GHB exhibited concentrations of 3.1-5.3 and 4.3 ng/mg, respectively, whereas the mean physiological level determined in this woman was 0.71 ng/mg, SD = 0.17 ng/mg. The authors advise a two-step hair sampling as evidence of GHB consumption: the first sample at the time of exposure to show the contamination by sweat of the proximal segment in case of recent administration with a significant rise of hair level at the root, and the second after at least 3 or 4 weeks to avoid this contamination and determine the levels incorporated in the hair matrix before, during, and after the exposure. PMID:14670136

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



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


?-Hydroxybutyric acid (GHB) is a metabolite of ?-aminobutyric acid (GABA) and a proposed neurotransmitter in the mammalian brain. We recently identified ?4?? 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 ?-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 ?4?3? 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. PMID:24973695

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



New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity ?-Hydroxybutyrate (GHB) Binding Sites  

PubMed Central

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Vogensen, Stine B.; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H.F.; Clausen, Rasmus P.



New synthesis and tritium labeling of a selective ligand for studying high-affinity ?-hydroxybutyrate (GHB) binding sites.  


3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [(3)H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [(3)H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Vogensen, Stine B; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H F; Clausen, Rasmus P



Cancer precursors.  


A significant proportion of cutaneous malignancies arise from well-defined precursor lesions that have often been present for many years. This provides an opportunity to reduce rates of skin cancer by recognition and treatment of these lesions. Precursors of keratinocytic malignancy, such as actinic keratoses and Bowen's disease, are extremely common in the older, white population and will frequently be encountered by generalist physicians in the context of examinations for noncutaneous conditions. Less common conditions, such as erythroplasia of Queyrat and nevus sebaceous, are associated with a higher risk of malignant change, and their recognition is therefore imperative. The management of the various precursors of melanoma remains controversial, as the exact risk of malignant transformation of many of these lesions is still unclear. PMID:9669604

Fitzgerald, D A



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


During the last few years ?-hydroxybutyric acid (GHB) and ?-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. PMID:23733593

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



Placement of gamma-butyrolactone in List I of the Controlled Substances Act (21 U.S.C. 802(34)). Drug Enforcement Administration, Justice. Final rule.  


Public Law 106-172, signed into law on February 18, 2000, and known as the "Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 1999," amends section 102(34) of the Controlled Substances Act as amended (CSA) by designating gamma-butyrolactone (GBL), the precursor to gamma-hydroxybutyric acid (GHB), as a List I chemical. Reflecting this change in stature, the Drug Enforcement Administration (DEA) is amending its regulation to reflect the status of GBL as a List I chemical subject to the requirements of the CSA and its regulations. Establishment of a threshold for GBL will be the subject of a separate rulemaking. Therefore, unless and until a threshold is established, any distribution of GBL is a regulated transaction as described by 21 CFR 1300.02(b)(28). All handlers of GBL must comply with the CSA regulatory requirements pertaining to List I chemicals as described in the body of this document. PMID:11010670



The effects and consequences of selected club drugs  

Microsoft Academic Search

Ecstasy (MDMA), gamma-hydroxybutyrate (GHB), ketamine, and methamphetamine are 4 examples of club drugs that are increasing in popularity. Although the pharmacological classifications of these drugs vary, MDMA has structural similarities to both amphetamine and the hallucinogen mescaline. Ketamine and GHB are anesthetic agents and methamphetamine is a long-acting psychostimulant. Medical visits for club drug-related toxicity have sharply increased across the

Thomas E. Freese; Karen Miotto; Cathy J. Reback



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


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. PMID:15099915

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



Simultaneous determination of ?-Hydroxybutyrate (GHB) and its analogues (GBL, 1.4-BD, GVL) in whole blood and urine by liquid chromatography coupled to tandem mass spectrometry.  


A simple liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for simultaneous identification and quantification of ?-hydroxybutyrate (GHB), ?-butyrolactone (GBL), 1.4-butanediol (1.4-BD), and ?-valerolactone (GVL) in whole blood from forensic cases. The sample preparation of whole blood involved protein precipitation by acidic methanol. Urine samples were diluted and evaluated in relation to a control at the cutoff concentration. Hexadeutero GHB (GHB-d(6)) was used as the internal standard. Separation was achieved by reversed-phase chromatography, and detection was by MS-MS in MRM mode. The linear range for all compounds was from 1.0 to 100 mg/kg in whole blood with a limit of quantification of about 1 mg/kg. The method was validated with regards to selectivity, recovery, accuracy and precision, and stability. The method is currently applied to investigations on suspected drug-facilitated sexual assaults, driving under the influence of drugs, and general intoxication with these substances. PMID:21219697

Johansen, Sys Stybe; Windberg, Charlotte Norup



Polyimide Precursor Solid Residuum  

NASA Technical Reports Server (NTRS)

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.

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



Precursors to pancreatic cancer.  


Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment. PMID:17996793

Hruban, Ralph H; Maitra, Anirban; Kern, Scott E; Goggins, Michael



?-Hydroxybutyrate (Xyrem) ameliorates clinical symptoms and neuropathology in a mouse model of Alzheimer's disease.  


The chronic decrease of brain amyloid-? (A?) peptides is an emerging therapeutic for Alzheimer's disease, but no such treatment has achieved clinical validation yet. In vivo, some brain proteases, including neprilysin, possess the ability of degrading A? and experimental data suggest their exploitation in strategies to reduce cerebral A? concentration. Previous studies have shown that pharmacologic doses of gamma-hydroxybutyrate (sodium oxybate or Xyrem) induce histone deacetylases (HDACs) inhibition and neprilysin gene expression. Here, we demonstrate that brain neprilysin overexpression induced in vivo by repeated gamma-hydroxybutyrate autoadministration reduces cerebral A? contents and prevents cognitive deficits in APPSWE mice. Oral gamma-hydroxybutyrate also counteracted phosphoramidon-induced brain neprilysin inhibition and A? accumulation. HDACs activities in SH-SY5Y cells were inhibited by gamma-hydroxybutyrate which did not affect amyloid peptide precursor intracellular domain. Together, our results suggest that gamma-hydroxybutyrate, acting via HDAC inhibition, upregulates neprilysin to reduce A? level and related memory deficits. Because gamma-hydroxybutyrate doses used herein are clinically relevant, our data suggest that chronic oral administration of gamma-hydroxybutyrate or its analogs may be considered for strategies against presymptomatic or established Alzheimer's disease. PMID:25457559

Klein, Christian; Mathis, Chantal; Leva, Géraldine; Patte-Mensah, Christine; Cassel, Jean-Christophe; Maitre, Michel; Mensah-Nyagan, Ayikoe G



Earthquakes: Hydrogeochemical precursors  

NASA Astrophysics Data System (ADS)

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.

Ingebritsen, S. E.; Manga, M.



Identification of Desirable Precursor Properties for Solution Precursor Plasma Spray  

NASA Astrophysics Data System (ADS)

In solution precursor plasma spray chemical precursor solutions are injected into a standard plasma torch and the final material is formed and deposited in a single step. This process has several attractive features, including the ability to rapidly explore new compositions and to form amorphous and metastable phases from molecularly mixed precursors. Challenges include: (a) moderate deposition rates due to the need to evaporate the precursor solvent, (b) dealing on a case by case basis with precursor characteristics that influence the spray process (viscosity, endothermic and exothermic reactions, the sequence of physical states through which the precursor passes before attaining the final state, etc.). Desirable precursor properties were identified by comparing an effective precursor for yttria-stabilized zirconia with four less effective candidate precursors for MgO:Y2O3. The critical parameters identified were a lack of major endothermic events during precursor decomposition and highly dense resultant particles.

Muoto, Chigozie K.; Jordan, Eric H.; Gell, Maurice; Aindow, Mark



Neuropharmacological profile of tetrahydrofuran in mice.  


Since the regulation of illicit gamma-hydroxybutyric acid (GHB) as a Federal Schedule I drug, the use of substitute chemical precursors such as gamma-butyrolactone (GBL) and 1,4-butanediol have emerged. Most recently there have been concerns about another potential analog of GHB, namely tetrahydrofuran (THF). While there is some suggestion that THF can be converted to GHB or GBL, little is known about the pharmacology of THF. Various doses of THF and GBL were studied in neurobehavioral tests to better characterize the pharmacology of THF. The TD(50)'s (with 95% confidence intervals) of THF for loss of the righting reflex and failure of performance on the rotarod test were 15.18 (11.88-19.39) and 7.00 (5.22-9.40) mmol/kg, respectively. These values were significantly greater (p<0.05) than those determined for GBL: 4.60 (3.25-6.51), and 0.85 (0.52-1.38) mmol/kg, respectively. The effects of THF on the impairment of motor function in the rotarod test were antagonized by pretreatment with the GABA(B) receptor antagonist CGP-35348 (200 mg/kg, i.p.). While both THF and GBL had depressant effects on open-field locomotor activity, the pattern of activity at the lower doses of THF and GBL were dissimilar. Chronic treatment with low dose THF (5 or 10 mmol/kg, i.p.) followed by acute challenge with THF (15 mmol/kg, i.p.) demonstrated tolerance to the observed sedative effects. While some of the mechanisms of the THF actions on the central nervous system appear likely to involve direct or indirect interactions with the GABA(B) receptor, some differences in its qualitative and quantitative pharmacology suggests other mechanisms are also likely involved in the observed neurobehavioral effects of these selected doses of THF in mice. PMID:17331547

Werawattanachai, Nuttiya; Towiwat, Pasarapa; Unchern, Surachai; Maher, Timothy J



Potential of IRMS technology for tracing gamma-butyrolactone (GBL).  


Popularity of gamma-hydroxybutyric acid (GHB) is fairly stable among drug users, while the consumption of its chemical precursor, gamma-butyrolactone (GBL), is a growing phenomenon. Although conventional analytical methods allow to detect this substance in various matrices, linking a trace and a source is still a difficult challenge. However, as several synthesis pathways and chemical precursors exist for the production of GBL, its carbon isotopic signature may vary extensively. For that purpose, a method has been developed to determine the carbon isotopes content of GBL by means of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The delta(13)C-values of 19 bulk samples purchased worldwide were in the range from -23.1 to -45.8 per thousand (SD<0.3 per thousand). Furthermore, testing on the purification of GBL by distillation has not been found to be consistent with such a large range of delta(13)C-values, which are likely to result from the isotopic composition of the organic precursors used to produce GBL together with the kinetic isotope effect associated with the synthesis routes. Finally, inter- and intra-variability measurements of the delta(13)C-values demonstrated the high potential of IRMS for discriminating between seizures of GBL and for source determination. PMID:20056363

Marclay, François; Pazos, Diego; Delémont, Olivier; Esseiva, Pierre; Saudan, Christophe



Seismo-Ionospheric Precursors  

NASA Astrophysics Data System (ADS)

Large earthquakes are often preceded or accompanied by signals of a different nature: electric, electromagnetic, or luminous, although seismic waves are the most obvious manifestation. Recently, seismo-ionospheric phenomena have received considerable discussions. To investigate possible seismo-ionospheric precursors, we statistically examine the relationship between electron density variations at the ionospheric F2 peak observed by a local ionosonde and 184 earthquakes with magnitude 5.0 or larger, which occurred in 170 days during 1994~1999 in the Taiwan area. Results demonstrate that the electron density abnormally decreases during the afternoon period, 1200~1800 LT, within 5 days before the earthquakes. The odds of the earthquakes with the precursor increasing in the earthquake magnitude but decreasing in the range between the epicenter and the ionosonde confirm the existence of an imminent seismo-ionospheric precursor.

Liu, J.; Chen, Y.; Chuo, Y.



Avalanche precursors R. Delannay,  

E-print Network

Avalanche precursors R. Delannay, Institut de Physique de Rennes, Université de Rennes 1, CNRS UMR at the top of the tray after some avalanches. · 4 or 5 large avalanches then observed during the slow of small "avalanches" which are recorded by a camera.2mm diameter beads #12;N. Nérone et al. Physica A 283

Gruner, Daniel S.



EPA Science Inventory

New methods of ambient air analysis were used to define more clearly the relationships between oxidants and their precursors. Non-methane hydrocarbons, NOx, O2, and oxidants were measured at the same time and location (Riverside, California). The ambient air data presented in thi...


Role of g -Aminobutyrate and g -Hydroxybutyrate in Plant Communication  

Microsoft Academic Search

The neurotransmitters gamma-aminobutyrate (GABA) and gamma-hydroxybutyrate (GHB) are found in virtually all prokaryotic and\\u000a eukaryotic organisms. The physiological roles of these metabolites in plants are not yet clear, but both readily accumulate\\u000a in response to stress through a combination of biochemical and transcriptional processes. GABA accumulation has been associated\\u000a with the appearance of extracellular GABA, and evidence is available for

Barry J. Shelp; Wendy L. Allan; Denis Faure


Sexual risk taking and club drug use across three age cohorts of HIV-positive gay and bisexual men in New York City  

Microsoft Academic Search

This study examined club drug use (i.e., cocaine, ecstasy, ketamine, gamma-hydroxybutyrate [GHB], and methamphetamine) and unprotected anal intercourse (UAI) in an ethnically and racially diverse sample of 166 New York City-based seropositive, club drug-using, gay and bisexual men, ages 19–61, and considered these behaviors in relation to age category (20s, 30s, and 40 +) and number of years living with

Molly K. Pappas; Perry N. Halkitis



The EM Earthquake Precursor  

NASA Astrophysics Data System (ADS)

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 directional techniques were employed, resulting in three mapped, potential epicenters. The remaining, weaker signals presented similar directionality results to more epicentral locations. In addition, the directional results of the Timpson field tests lead to the design and construction of a third prototype antenna. In a laboratory setting, experiments were created to fail igneous rock types within a custom-designed Faraday Cage. An antenna emplaced within the cage detected EM emissions, which were both reproducible and distinct, and the laboratory results paralleled field results. With a viable system and continuous monitoring, a fracture cycle could be established and observed in real-time. Sequentially, field data would be reviewed quickly for assessment; thus, leading to a much improved earthquake forecasting capability. The EM precursor determined by this method may surpass all prior precursor claims, and the general public will finally receive long overdue forecasting.

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




SciTech Connect

We have studied three most recent precursor flares in the light curve of the blazar OJ 287 while invoking the presence of a precessing binary black hole in the system to explain the nature of these flares. Precursor flare timings from the historical light curves are compared with theoretical predictions from our model that incorporate effects of an accretion disk and post-Newtonian description for the binary black hole orbit. We find that the precursor flares coincide with the secondary black hole descending toward the accretion disk of the primary black hole from the observed side, with a mean z-component of approximately z{sub c} = 4000 AU. We use this model of precursor flares to predict that precursor flare of similar nature should happen around 2020.96 before the next major outburst in 2022.

Pihajoki, P.; Berdyugin, A.; Lindfors, E.; Reinthal, R.; Sillanpaeae, A.; Takalo, L. [Tuorla Observatory, Department of Physics and Astronomy, University of Turku, FI-21500 Piikkioe (Finland)] [Tuorla Observatory, Department of Physics and Astronomy, University of Turku, FI-21500 Piikkioe (Finland); Valtonen, M.; Nilsson, K. [Finnish Centre for Astronomy with ESO, University of Turku, FI-21500 Piikkioe (Finland)] [Finnish Centre for Astronomy with ESO, University of Turku, FI-21500 Piikkioe (Finland); Zola, S.; Koziel-Wierzbowska, D. [Astronomical Observatory, Jagiellonian University, ul. Orla 171, PL-30-244 Krakow (Poland)] [Astronomical Observatory, Jagiellonian University, ul. Orla 171, PL-30-244 Krakow (Poland); Liakos, A. [Department of Astrophysics, Astronomy and Mechanics, University of Athens, GR 157 84 Zografos, Athens, Hellas (Greece)] [Department of Astrophysics, Astronomy and Mechanics, University of Athens, GR 157 84 Zografos, Athens, Hellas (Greece); Drozdz, M.; Winiarski, M.; Ogloza, W. [Mount Suhora Observatory, Pedagogical University, ul. Podchorazych 2, PL-30-084 Krakow (Poland)] [Mount Suhora Observatory, Pedagogical University, ul. Podchorazych 2, PL-30-084 Krakow (Poland); Provencal, J. [Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States)] [Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States); Santangelo, M. M. M. [O.A.C. Osservatorio Astronomico di Capannori, Via di Valle, I-55060 Vorno, Capannori (Italy)] [O.A.C. Osservatorio Astronomico di Capannori, Via di Valle, I-55060 Vorno, Capannori (Italy); Salo, H. [Department of Physical Sciences, University of Oulu, P.O. Box 3000, FI-90014 University of Oulu (Finland)] [Department of Physical Sciences, University of Oulu, P.O. Box 3000, FI-90014 University of Oulu (Finland); Chandra, S.; Ganesh, S.; Baliyan, K. S., E-mail: [Astronomy and Astrophysics Division, Physical Research Laboratory, Ahmedabad 380009 (India); and others



Brillouin precursors in Debye media  

E-print Network

We theoretically study the formation of Brillouin precursors in Debye media. We point out that the precursors are only visible at propagation distances such that the impulse response of the medium is essentially determined by the frequency-dependence of its absorption and is practically Gaussian. By simple convolution, we then obtain explicit analytical expressions of the transmitted waves generated by reference incident waves, distinguishing precursor and main signal by physical arguments. These expressions are in good agreement with the signals obtained in numerical or real experiments performed on water and explain some features of these signals that remained mysterious or unnoticed. In addition, we show quite generally that the shape of the Brillouin precursor appearing alone at large enough propagation distance and the law giving its amplitude as a function of this distance do not depend on the precise form of the incident wave but only on its integral properties. The incidence of a static conductivity o...

Macke, Bruno




EPA Science Inventory

The removal of trihalomethane precursors by coagulation was studied with low turbidity, low alkalinity waters containing high levels of aquatic humic matter. Jar tests were conducted with synthetic and natural waters using alum, high-molecular-weight polymers, cationic polymers, ...


Precursors of Hypertension: A Review  

PubMed Central

Recent advances in hypertension therapy have been remarkable; however, much less is known about those precursors that facilitate preventive and early intervention measures. This review of the literature indicates that relevant precursors are early elevated casual systolic blood pressures, positive family history, and obesity in females. Additional predisposing or enhancing factors point to high sodium ingestion, heavy smoking, and high socioecologic stress. Evidence for a high-risk hypertensive personality is not conclusive. There is a paucity of longitudinal data on hypertension in the black population. PMID:6864814

Thomas, John; Neser, William B.; Thomas, Johniene; Semenya, Kofi; Green, Donald R.



Optical precursor in Rb Vapor  

NASA Astrophysics Data System (ADS)

Picosecond pulses with center wave length 780nm are directed through a hot Rubidium cell. The input pulse are shaped with dazzler to be Gaussian, modulated Gaussian or square shape pulses. The output pulses are detected by streak camera. Simulation results of output pulse shape are presented. Optical precursors are observed in the simulation results. Some issues in the simulations are also discussed.

Yang, Wenlong; Sokolov, Alexei



Preparation of superconductor precursor powders  


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.

Bhattacharya, Raghunath (Littleton, CO); Blaugher, Richard D. (Evergreen, CO)



1995 Accident Sequence Precursor (ASP) Program results  

Microsoft Academic Search

The Accident Sequence Precursor (ASP) Program involves the systematic review and evaluation of operational events that have occurred at light-water reactors to identify and categorize precursors to potential severe core damage accident sequences. The results of the ASP Program are published in an annual report. The most recent report, which contains the precursors for 1995, is NUREG\\/CR-4674, Volume 23, Precursors

M. D. Muhlheim; R. J. Belles; J. W. Cletcher; D. A. Copinger; B. W. Dolan; J. W. Minarick



Precursors of Short Gamma-Ray Bursts  

NASA Technical Reports Server (NTRS)

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.

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



New Worlds Observer Precursor Mission  

NASA Astrophysics Data System (ADS)

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.

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



Weighing in on Adipocyte Precursors  

PubMed Central

Obesity, defined as an excessive increase in white adipose tissue (WAT), is a global health epidemic. In obesity, WAT expands by increased adipocyte size (hypertrophy) and number (hyperplasia). The location and cellular mechanisms of WAT expansion greatly affect the pathogenesis of obesity. However, the cellular and molecular mechanisms regulating adipocyte size, number and depot-dependent expansion in vivo remain largely unknown. This perspective summarizes previous work addressing adipocyte number in development and obesity and discusses recent advances in the methodologies, genetic tools, and characterization of in vivo adipocyte precursor cells allowing for directed study of hyperplastic WAT growth in vivo. PMID:24239569

Berry, Ryan; Jeffery, Elise; Rodeheffer, Matthew S.



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

PubMed Central

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

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



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


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 (1)H-NMR, (1)H-COSY, and (1)H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed. PMID:25018772

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



Formation pathways of gamma-butyrolactone from the furan ring of tegafur during its conversion to 5-fluorouracil.  


Tegafur (FT) is a 5-fluorouracil (5-FU) prodrug that has been clinically used for various cancer chemotherapies. The following metabolites of FT were identified in patients: 5-FU, fluoro-beta-alanine, and gamma-butyrolactone (GBL) and its acidic form, gamma-hydroxybutyrate (GHB). GBL/GHB, which is probably generated from the furan ring of FT, inhibits tumor cell angiogenesis, contributing to the antitumor effect of FT-based therapies. In the present study, we identified the metabolites formed from the furan ring of FT by CYP2A6 and thymidine phosphorylase (TPase) using 2,4-dinitrophenylhydrazine derivatization procedures and clarified the metabolic pathway of FT to GBL/GHB. Succinaldehyde (SA) and 4-hydroxybutanal (4-OH-BTL) were produced as the metabolites because of the cleavage of the furan ring of FT during its conversion to 5-FU in cDNA-expressed CYP2A6 and purified TPase, respectively; however, GBL/GHB was hardly detected in cDNA-expressed CYP2A6 and purified TPase. GBL/GHB was formed after human hepatic microsomes or cDNA-expressed CYP2A6 mixed with cytosol were incubated with FT. Furthermore, 4-OH-BTL was converted to GBL/GHB in the microsomes and cytosol. These results suggest that GBL/GHB is generated from FT through the formation of SA and 4-OH-BTL but not directly from FT. Furthermore, the amount of 5-FU and GBL/GHB formed in the hepatic S9 was markedly decreased in the presence of a CYP2A6 inhibitor, suggesting that GBL/GHB may be mainly generated through the CYP2A6-mediated formation of SA. PMID:20463005

Yamamiya, Ikuo; Yoshisue, Kunihiro; Matsushima, Eiji; Nagayama, Sekio



Precursors for Carbon Nitride Synthesis  

SciTech Connect

Nano structured carbon nitride films were prepared by pyrolysis assisted chemical vapour deposition. Pyrrole (C{sub 4}H{sub 5}N), Pyrrolidine (C{sub 4}H{sub 9}N), Azabenzimidazole (C{sub 6}H{sub 5}N{sub 3}) and Triazine (C{sub 6}H{sub 15}N{sub 3}) were used as precursors. The vibrational modes observed for C-N and C = N from FTIR spectra confirms the bonding of nitrogen with carbon. XPS core level spectra of C 1s and N 1s also show the formation of bonding between carbon and nitrogen atoms. The nitrogen content in the prepared samples was found to be around 25 atomic %.

Prashantha, M.; Gopal, E. S. R.; Ramesh, K. [Department of Physics, Indian Institute of Science, Bangalore 560012 (India)



Molecular and polymeric ceramic precursors  

SciTech Connect

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.

Sneddon, L.G.



Molecular and polymeric ceramic precursors  

SciTech Connect

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 in inorganic and organometallic chemistry to the production of technologically important non-oxide ceramics, such as boron nitride, boron carbide and metal borides. 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 an exploration of the solid state properties of the ceramics that have been produced in these studies.

Sneddon, L.G.



Carbon Fibers from Polyethylene-Based Precursors  

Microsoft Academic Search

Polyethylene fibers are attractive as carbon fiber precursors due to their high carbon content and ease of manufacture. Also, highly ordered and oriented fibers with extraordinary physical and mechanical properties are available today. However, being thermoplastic fibers, they soften or melt at a fairly low temperature, losing their fiber form. These precursors have to be stabilized by introducing cross links

Dong Zhang; Gajanan S. Bhat



Response of inorganic PM to precursor concentrations  

Microsoft Academic Search

An inorganic aerosol equilibrium model is used to investigate the response of inorganic particulate matter (PM) concentrations with respect to the precursor concentrations of sulfuric acid, ammonia, and nitric acid over a range of temperatures and relative humidities. Diagrams showing regions of PM response to precursor concentrations are generated, thus allowing the qualification of assumptions concerning the response of PM

Asif S. Ansari; Spyros N. Pandis



Leading time domain seismic precursors  

NASA Astrophysics Data System (ADS)

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 other precursors will enhance significantly the prediction of significant earthquakes.

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



Method of texturing a superconductive oxide precursor  


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.

DeMoranville, Kenneth L. (Jefferson, MA); Li, Qi (Marlborough, MA); Antaya, Peter D. (Sutton, MA); Christopherson, Craig J. (Worcester, MA); Riley, Jr., Gilbert N. (Marlborough, MA); Seuntjens, Jeffrey M. (Bangau, SG)



Precursor films in wetting phenomena  

E-print Network

The spontaneous spreading of non-volatile liquid droplets on solid substrates poses a classic problem in the context of wetting phenomena. It is well known that the spreading of a macroscopic droplet is in many cases accompanied by a thin film of macroscopic lateral extent, the so-called precursor film, which emanates from the three-phase contact line region and spreads ahead of the latter with a much higher speed. Such films have been usually associated with liquid-on-solid systems, but in the last decade similar films have been reported to occur in solid-on-solid systems. While the situations in which the thickness of such films is of mesoscopic size are rather well understood, an intriguing and yet to be fully understood aspect is the spreading of microscopic, i.e., molecularly thin films. Here we review the available experimental observations of such films in various liquid-on-solid and solid-on-solid systems, as well as the corresponding theoretical models and studies aimed at understanding their formation and spreading dynamics. Recent developments and perspectives for future research are discussed.

M. N. Popescu; G. Oshanin; S. Dietrich; A. -M. Cazabat



Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and gamma-butyrolactone in rhesus monkeys.  


Metabolic precursors and prodrugs of gamma-hydroxybutyrate (GHB), including 1,4-butanediol (BDL) and gamma-butyrolactone (GBL), have sedative and anesthetic effects and might have positive reinforcing effects. BDL and GBL were evaluated using behavioral procedures that measure positive reinforcing effects and discriminative stimulus effects of drugs that modulate gamma-aminobutyric acid (GABA) at the GABA(A) receptor complex. One group of rhesus monkeys could respond for saline or the barbiturate methohexital (i.v.) in a self-administration paradigm. Two other groups of monkeys discriminated the barbiturate pentobarbital (i.g.) or the benzodiazepine midazolam (s.c.) from saline in a drug discrimination paradigm; another group of monkeys was treated with the benzodiazepine diazepam (5.6 mg/kg/day, p.o.) and discriminated the benzodiazepine antagonist flumazenil (s.c.) from vehicle. In self-administration experiments, methohexital and not BDL (0.1-3.2 mg/kg/injection) or GBL (0.1-3.2 mg/kg/injection) reliably maintained responding above saline levels. BDL and GBL, up to doses that suppressed responding, did not substitute for pentobarbital, midazolam or flumazenil. The onset of action for both drugs to decrease response rate was delayed (90 min for GBL and 150 min for BDL). These results suggest that any abuse-related effects of BDL and GBL are qualitatively different from the abuse-related effects of GABA(A) receptor modulators and further indicate that BDL and GBL do not have positive reinforcing effects in rhesus monkeys experienced with self-administration of a short-acting sedative-hypnotic. PMID:12679147

McMahon, Lance R; Coop, Andrew; France, Charles P; Winger, Gail; Woolverton, William L



Mechanism(s) regulating inhibition of thymidylate synthase and growth by gamma-L-glutaminyl-4-hydroxy-3-iodobenzene, a novel melanin precursor, in melanogenic melanoma cells.  


A proposed mechanism for the melanoma specific activity of phenolic amines is based upon the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates. In this study, we synthesized an iodinated analog of gamma-L-glutaminyl-4-hydroxybenzene (GHB) with increased antimelanoma activity in both human and murine melanoma cell lines. GHB and gamma-L-glutaminyl-4-hydroxy-3-iodobenzene (I-GHB) were shown to be substrates for both mammalian and mushroom tyrosinase. Glutathione, a cellular antioxidant, inhibited tyrosinase mediated formation of gamma-L-glutaminyl-3,4-benzoquinone (GBQ) from GHB, inhibited melanin production, and blocked the inhibition of the enzyme thymidylate synthase by oxidized GHB. Buthionine sulfoximine (BSO) depletion of cellular glutathione enhanced the growth inhibitory activity and the inhibition of in situ thymidylate synthase by phenolic amines in melanoma cells. GHB and I-GHB were shown to be approximately 5- and 10-fold more cytotoxic, respectively, in highly metastatic B16-BL6 cells than in weakly metastatic B16-F1 cells with approximately equal tyrosinase activity. B16-BL6 cells had approximately 20-fold higher gamma-glutamyltranspeptidase (gamma-GTPase) activity than B16-F1 cells which suggested the possible involvement of this enzyme in the activation of the cytotoxicity of the phenolic amines. 4-Aminophenol, a product of gamma-GTPase reaction with GHB, was a substrate for tyrosinase and a potent inhibitor of in situ thymidylate synthase activity in melanogenic cells. In pigmented melanoma cells containing the enzyme tyrosinase, the quinone mediated mechanism of phenolic amine cytotoxicity may be uniquely important and the cellular antioxidant glutathione essential in the detoxification of these quinone-generated intermediates. PMID:8435097

Prezioso, J A; Damodaran, K M; Wang, N; Bloomer, W D



A precursor to the Venus bow shock  

NASA Technical Reports Server (NTRS)

This paper describes the observations by the Pioneer-Venus-Orbiter Langmuir probe of the low-density Venus bow shock precursor, i.e., a region of electron and ion-current enhancements just upstream from the Venus bow shock. It is suggested that the precursor signatures represent the effects of a small population of energetic ions in this region. Several possible planetary sources of these ions are considered. The paper also discusses the Langmuir probe measurement technique itself as it applies to the very low densities of the precursor.

Brace, L. H.; Theis, R. F.; Curtis, S. A.; Parker, L. W.



Joint Robotic Precursor Activity: Providing Strategic Knowledge to  

E-print Network

Joint Robotic Precursor Activity: Providing Strategic Knowledge to Inform Future Exploration Dr. Michael J. Wargo, Chief Exploration Scientist #12;Joint Robotic Precursor Activity (JRPA) Overview · To meet this goal, NASA will jointly fund and conduct Robotic Precursor Activities

Waliser, Duane E.


The molecular evolution of the allatostatin precursor in cockroaches  

E-print Network

The molecular evolution of the allatostatin precursor in cockroaches XAVIER BELLE´Sa , LAURIE A that specify the preproallatostatin precursor for the cockroaches, Blatta orientalis, Blattella germanica punctata and Periplaneta americana reported previously. The precursors of all these cockroach species

Belles, Xavier


A Population of Oligodendrocytes Derived From Multipotent Neural Precursor Cells  

E-print Network

A Population of Oligodendrocytes Derived From Multipotent Neural Precursor Cells Expresses, Georgia Because oligodendrocytes and their precursors possess receptors for classical transmitters in oligodendrocyte function. We used mitogen- proliferated multipotent neuroepithelial precursors (neurospheres

Manitoba, University of


Long range transport of acid rain precursors  

E-print Network

A model of the long range transport of primary and secondary pollutants derived by Fay and Rosenzweig (1) is applied to the problem of the transport of acid rain precursors. The model describes the long term average (annual ...

Fay, James A.



Biochemical Removal of HAP Precursors From Coal  

SciTech Connect

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.

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



Hydridosiloxanes as precursors to ceramic products  


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.

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



Hydridosiloxanes as precursors to ceramic products  


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.

Blum, Yigal D. (San Jose, CA); Johnson, Sylvia M. (Piedmont, CA); Gusman, Michael I. (Palo Alto, CA)



Locating evolutionary precursors on a phylogenetic tree.  


Conspicuous innovations in the history of life are often preceded by more cryptic genetic and developmental precursors. In many cases, these appear to be associated with recurring origins of very similar traits in close relatives (parallelisms) or striking convergences separated by deep time (deep homologies). Although the phylogenetic distribution of gain and loss of traits hints strongly at the existence of such precursors, no models of trait evolution currently permit inference about their location on a tree. Here we develop a new stochastic model, which explicitly captures the dependency implied by a precursor and permits estimation of precursor locations. We apply it to the evolution of extrafloral nectaries (EFNs), an ecologically significant trait mediating a widespread mutualism between plants and ants. In legumes, a species-rich clade with morphologically diverse EFNs, the precursor model fits the data on EFN occurrences significantly better than conventional models. The model generates explicit hypotheses about the phylogenetic location of hypothetical precursors, which may help guide future studies of molecular genetic pathways underlying nectary position, development, and function. PMID:23206146

Marazzi, Brigitte; Ané, Cécile; Simon, Marcelo F; Delgado-Salinas, Alfonso; Luckow, Melissa; Sanderson, Michael J



Polyimide precursors for carbon molecular sieve membranes  

NASA Astrophysics Data System (ADS)

Carbon molecular sieve (CMS) membranes were produced for gas separations by pyrolyzing an asymmetric hollow fiber composed of a polyimide. Using an industrially obtained precursor fiber, the role of pyrolysis conditions on CMS membrane performance was examined. In order to examine the role of precursor morphology and composition on carbon membrane performance, fibers composed of Matrimidsp°ler 5218 were spun and pyrolyzed. Using vacuum pyrolysis at 550sp°C, a CMS membrane was produced that exhibited permselective performance that was above the "upper bound" for air separations. In order to create "robustness" in the pyrolysis process for potentially "nonideal" fiber morphologies, several processing variables were investigated-pyrolysis in a vacuum versus an inert purge gas, the purge gas flow rate, the type of purge gas, residual oxygen content in the purge gas, and the pyrolysis temperature. The role of the support material was examined and a potential model for precursor pyrolysis was constructed. Utilizing previously studied techniques, asymmetric hollow fibers were spun to create a variety of morphologies and compositions. While some of the fibers could be considered "good" polyimide membranes, some of the fibers would be considered "nonideal". For the precursor morphology and composition studies, certain characteristics were chosen for investigation. Hollow fibers having different inner and outer diameters were produced. The thickness and integrity of the skin layer as well as the overall fiber density were also controlled. The morphology of the fiber substructure was varied. The composition of the fibers was a mixture of the polyimide Matrimidsp°ler 5218 and the epoxy resin F-2300, which have "high" and "low" carbon yields, respectively. Having produced and characterized a variety of precursor fibers, carbon membranes were produced, primarily using a vacuum pyrolysis protocol at 550sp°C. The effects of different precursor fibers compositions, densities, and dimensions on carbon membrane performance were studied. The role of precursor substructure and skin layer morphologies was also examined.

Geiszler, Vincent Carl


Precursors of storage proteins in Lupinus angustifolius.  

PubMed Central

The proteins that are synthesized during differentiation and development in the cotyledons of Lupinus angustifolius L. were characterized both in situ and after purification. The proteins present in situ were separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and subjected to 'Western'-blot analysis to identify immunologically related polypeptides. The major storage proteins of the lupin, conglutins alpha and beta, were both present in juvenile tissue only as higher Mr precursors. For conglutin beta, a family of at least three polypeptides of Mr 66 000-72 000 accumulated during the earliest phases of protein synthesis in the developing cotyledon (20-28 days after flowering). Later in development each of these polypeptides disappeared and there was the concurrent appearance in the cotyledon of the lower-Mr fragments characteristic of mature conglutin beta. For conglutin alpha, an equivalent family of precursor polypeptides of Mr 60 000-83 000 was detected. Multiple internal sites for proteolytic cleavage of all these precursors appeared to be present. However, processing of the precursors was sufficiently slow to allow them to accumulate to over 50% of total soluble protein in juvenile tissue. The precursors were purified by column chromatography under non-dissociating conditions and shown by ultracentrifugation to be multimeric proteins with Mr values in the range 150 000-200 000. Images Fig. 1. Fig. 3. Fig. 4. Fig. 6. Fig. 7. PMID:6548131

Gayler, K R; Boadle, B G; Snook, M; Johnson, E D



Current topics on precursors to pancreatic cancer.  


Prognosis of invasive pancreatic ductal adenocarcinoma is bleak and the vast majority of patients with pancreatic cancer die of their disease. The detection and treatment of the non-invasive precursor lesions of pancreatic cancer offer the opportunity to cure this devastating disease and therefore great efforts are being made to identify the precursors to pancreatic cancer. Several distinct precursor lesions have been identified. Mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic intraepithelial neoplasias (PanINs) all harbor varying degrees of dysplasia and stepwise accumulation of genetic alterations, suggesting progression of these lesions from benign toward malignant neoplasms. MCNs have a characteristic ovarian-type stroma. About one-third of MCNs are associated with invasive carcinoma of ductal phenotype. IPMNs are recently established clinical entity with characteristic features of mucin hypersecretion and duct dilatation. Some IPMNs are associated with invasive carcinoma and IPMNs are recognized precursors to pancreatic cancer. PanINs are microscopic proliferative lesions arising from any parts of the pancreatic duct system. Low grade PanINs are commonly found in pancreatic ducts of elder individuals, while high grade PanINs, previously called carcinoma in situ/severe ductal dysplasia, may eventually give rise to invasive pancreatic cancer. Appropriate clinical managements are requisite for patients with MCNs, IPMNs and PanINs. Further investigation of these precursor lesions is expected to reduce the mortality from pancreatic cancer. PMID:17357272

Takaori, K; Hruban, R H; Maitra, A; Tanigawa, N



Nozzle designs with pitch precursor ablatives  

NASA Technical Reports Server (NTRS)

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.

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



Sequestration and Transport of Lignin Monomeric Precursors  

SciTech Connect

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.

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



Polymeric precursors for fibers and matrices  

NASA Technical Reports Server (NTRS)

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.

Hurwitz, Frances I.



Optical Precursor in Hot Rubidium Vapor  

NASA Astrophysics Data System (ADS)

A pico-second pulse with center wavelength about 795nm was sent through a hot rubidium (Rb) cell. The output pulse was detected by a streak camera with 2 pico-second resolution. The experiment data showed the original pulse separates to a main pulse and a precursor which travels faster than the main pulse. This gives some experiment evidence of the formation of precursor when a step-function-shape electromagnetic pulse travels through a Lorentz absorber, which was proposed by Dr. A. Sommerfeld and Dr. L. Brillouin about 100 years ago.

Yang, Wenlong; Springer, Matthew; Kolomenski, Alexandre; Kattawar, George; Sokolov, Alexei




EPA Science Inventory

Monitoring was conducted during the summer of 1990 to address the measurement of ozone (0a) and ozone precursors in Atlanta, Georgia. ata was collected using automated gas chromatography. esolved individual species were detected via a flame ionization detector (FID) and an electr...


Alumina precursors produced by gel combustion  

Microsoft Academic Search

Alumina precursor produced by a gel combustion method using aluminum nitrate and citric acid as raw materials was investigated. Thermodynamic calculation of the combustion reaction shows that as the citrate-to-nitrate ratio ? increases, the enthalpy of reaction and adiabatic flame temperatures also increase. The DSC analysis indicates that the combustion temperature of the gel decreases, as the citrate content in

Jiang Li; Yusong Wu; Yubai Pan; Jingkun Guo



School Violence: Prevalence, Precursors, and Prevention.  

ERIC Educational Resources Information Center

Reviews types of school violence students confront, including a frequent precursor thereto: bullying. Discusses positive and negative aspects of current approach to school violence prevention such as surveillance, zero-tolerance policies, anti-bullying programs. Describes components of model school violence-prevention program. (Contains 38…

Juvonen, Jaanna



The amyloid precursor protein: beyond amyloid  

Microsoft Academic Search

The amyloid precursor protein (APP) takes a central position in Alzheimer's disease (AD) pathogenesis: APP processing generates the ?-amyloid (A?) peptides, which are deposited as the amyloid plaques in brains of AD individuals; Point mutations and duplications of APP are causal for a subset of early onset of familial Alzheimer's disease (FAD). Not surprisingly, the production and pathogenic effect of

Hui Zheng; Edward H Koo



Superconductor precursor mixtures made by precipitation method  


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.

Bunker, Bruce C. (Albuquerque, NM); Lamppa, Diana L. (Albuquerque, NM); Voigt, James A. (Albuquerque, NM)



Biochemical Removal of HAP Precursors from Coal  

SciTech Connect

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.

Gregory J. Olson



40 CFR 766.38 - Reporting on precursor chemical substances.  

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40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2013 CFR

... false Reporting on precursor chemical substances. 766.38 Section...DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a)...



40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2011 CFR

... false Reporting on precursor chemical substances. 766.38 Section...DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a)...



40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2012 CFR

... false Reporting on precursor chemical substances. 766.38 Section...DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a)...



40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2010 CFR

... false Reporting on precursor chemical substances. 766.38 Section...DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a)...



Studies of Enzymes in Mitochondrial DNA Precursor Synthesis  

E-print Network

Studies of Enzymes in Mitochondrial DNA Precursor Synthesis Regulatory Mechanisms for Human;Studies of Enzymes in Mitochondrial DNA Precursor Synthesis - Regulatory Mechanisms for Human Thymidine Kinase 2 and Deoxyguanosine Kinase Abstract As important enzymes in mitochondrial nucleotide salvage


Magnetic field amplification in supernova shock precursor  

NASA Astrophysics Data System (ADS)

Galactic cosmic rays are believed to be mostly accelerated at supernova shocks. However, the interstellar magnetic field is too weak to efficiently accelerate galactic cosmic rays up to the highest energies. A stronger magnetic field in the preshock region could provide the efficiency required. Cosmic ray streaming instability has been claimed to be responsible for the amplification of precursor magnetic fields. An alternative mechanism has been proposed in which the cosmic ray pressure gradient forms the shock precursor and drives turbulence, amplifying the magnetic field via the small-scale dynamo. We explore this last scenario through 3-D MHD numerical simulations. We show under which conditions an efficient amplification of the magnetic field is achieved.

Del Valle, Maria Victoria; Lazarian, Alex


Precursors to radiopharmaceutical agents for tissue imaging  


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.

Srivastava, Prem C. (Oak Ridge, TN); Knapp, Jr., Furn F. (Oak Ridge, TN)



Tungsten carbide (WC) synthesis from novel precursors  

Microsoft Academic Search

This paper deals with the production and properties of tungsten carbide (WC) powders from novel carbon coated precursors. The process has two steps in which the oxide powders were first coated with carbon by cracking of a hydrocarbon gas, propylene (C3H6), secondly mixed with a substantial amount of carbon black, and finally treated at temperatures in the range of 600-1400°C

Rasit Koc; Suneel K Kodambaka



Precursors of endometrial and ovarian carcinoma  

Microsoft Academic Search

This review discusses precursor lesions of endometrial and ovarian carcinoma with an emphasis on the unique molecular alterations\\u000a that have led to the development of binary classification schemes for tumors of both the endometrium and ovary. While such\\u000a a system is well established for endometrial carcinoma, only recently has a binary classification scheme been proposed for\\u000a ovarian carcinoma. For both,

Robert J. Kurman; Thomas G. McConnell



Barium hexaferrite synthesis by oxalate precursor route  

Microsoft Academic Search

Magnetic materials are important electronic materials that have a wide range of industrial and commercial applications. Barium hexaferrite (BaFe12O19), is of great importance as permanent magnets, particularly for magnetic recording as well as in microwave devices. An aim of this study was to synthesize stoichiometric and single phase barium hexaferrite by a technique of oxalate precursor. Effect of different annealing

Q. Mohsen



Current understanding of precursors to pancreatic cancer.  


Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors, i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian-type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low-grade PanINs. Mucin expression profiles suggest intestinal-type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB-type IPMNs progress toward ductal adenocarcinoma. It is a well-described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step-wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas. PMID:17520195

Takaori, Kyoichi



Scalar model for frictional precursors dynamics  

PubMed Central

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

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



Scalar model for frictional precursors dynamics.  


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

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



Colorectal serrated pathway cancers and precursors.  


The serrated pathway (SP) can be viewed as two parallel, but partially overlapping, arrays of colorectal precursor lesions, and their respective endpoint carcinomas, that are distinct from those of the conventional adenoma-carcinoma sequence (APC-pathway). In this review we focus at the outset on the clinical impact, pathological features, molecular genetics and biological behaviours of the various SP cancers. Then we summarize the clinicopathological features, classification and molecular profiles of the two main precursor lesions that anchor the respective pathways: (i) sessile serrated adenoma/polyp (SSA/P), also called sessile serrated lesion (SSL), and (ii) traditional serrated adenoma (TSA). Activating mutations of the RAS-RAF-MAPK pathway initiate and sustain the lesions of the SP, and CpG island methylation of the promoter regions of tumour suppressor and DNA repair genes play the major role in their neoplastic progression. The SP includes microsatellite stable (MSS) carcinomas that are among the most biologically aggressive colorectal carcinomas (CRC), and also accounts for the great preponderance of sporadic hypermutated, mismatch repair (MMR)-deficient or microsatellite instable (MSI) CRC. The identification, removal and appropriate classification of at-risk SP precursors and surveillance of individuals who harbour these lesions present a challenge and opportunity for CRC prevention and mortality reduction. PMID:25263173

O'Brien, Michael J; Zhao, Qing; Yang, Shi



Disinfection byproduct formation from lignin precursors.  


Lignin is the most abundant aromatic plant component in terrestrial ecosystems. This study was conducted to determine the contribution of lignin residues in natural water to the formation of disinfection byproducts (DBPs) in drinking water. We investigated the formation of different classes of DBPs from lignin model compounds, lignin polymers, and humic substances using two common disinfection techniques, chlorination and chloramination. The contributions of lignin to the overall formation of DBPs from these organic products were determined based on the observed abundances of individual lignin phenols and their DBP yields. Model lignin phenols generally produced higher trichloroacetic acid (TCAA) yields than chloroform and dichloroacetic acid (DCAA) during chlorination. Lignin phenols generally produced higher DBP yields but lower percentages of unknown total organic halogen compared to bulk humic substances and lignin polymers. The relative significance of lignin phenols as chlorination DBP precursors generally follows the order of TCAA > DCAA&chloroform. The relative significance of lignin phenols to DBP formation by chloramination follows the order: TCAA > DCAA&DCAN > chloroform. Overall, lignin phenols are more important as TCAA precursors than as chloroform and DCAA precursors. PMID:25016301

Hua, Guanghui; Kim, Junsung; Reckhow, David A



A polymer precursor route to metal borides  

SciTech Connect

A synthetic route to metal borides that employs processable polymer/metal-oxide precursors is described. The precursor materials are obtained by dispersing metal oxides in the decaborane-dicyanopentane polymer, ([minus]B[sub 10]H[sub 12]NC-(CH[sub 2])[sub 5]-CN-)[sub x]. Subsequent pyrolyses of the dispersions above 1400[degrees]C afford metal borides, including TiB[sub 2], ZrB[sub 2], HfB[sub 2], NbB[sub 2], and TaB[sub 2] in high chemical and ceramic yields. The metal boride powders were found to be highly crystalline with grain sizes dependent on processing temperatures. The ceramic conversion reactions are proposed to involve in situ generation of amphorous BCN materials, followed by solid-state reduction of the metal oxides to produce the final boride products. Precursor dispersions formed from submicron metal oxides, along with a suitable surfactant, can be used to generate an emulsion from which metal boride coatings on graphite plates can be obtained. 17 refs., 16 figs., 3 tabs.

Su, K.; Sneddon, L.G. (Univ. of Pennsylvania, Philadelphia, PA (United States))



Scalar model for frictional precursors dynamics  

E-print Network

Recent experiments indicate that frictional sliding occurs by the 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 such 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 the 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 the transition to sliding, and the normal and shear internal stress distributions close to the slider-substrate interface. Moreover, it allows to assess which experimental 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, which helps to explain why earthquake forecasting methods based only on accumulated slip and Coulomb stress monitoring are often ineffective.

Alessandro Taloni; Andrea Benassi; Stefan Sandfeld; Stefano Zapperi



Cellular Kinetics of Perivascular MSC Precursors  

PubMed Central

Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration. PMID:24023546

Chen, William C. W.; Murray, Iain R.; Lazzari, Lorenza; Huard, Johnny; Péault, Bruno



Effect of Comonomers on Finishing Behavior of Carbon Fiber Precursors  

Microsoft Academic Search

Finishing kinetics of acrylic precursor fibers was studied by using a new CGB-1 finish. Effects of different comonomers including vinyl pyrrolidone, acrylamide and methyl acrylate on finishing behavior of acrylic precursors were discussed. Diffusion coefficients of the finish were calculated by the Crank’s equation. It is shown that the precursor fibers with the CGB-1 finish do not have fluff, broken

Chen Hou; Rongjun Qu; Liang Ying; Chengguo Wang



Reverse tracing of short-term earthquake precursors  

Microsoft Academic Search

We introduce a new approach to short-term earthquake prediction named “Reverse Tracing of Precursors” (RTP), since it considers precursors in reverse order of their appearance. First, we detect the “candidates” for the short-term precursors; in our case, these are newly introduced chains of earthquakes reflecting the rise of an earthquake correlation range. Then we consider each chain, one by one,

V. Keilis-Borok; P. Shebalin; A. Gabrielov; D. Turcotte



Short- and Middle-Term Earthquake Precursors  

NASA Astrophysics Data System (ADS)

Earthquakes are commonly believed to result from slip instability along a fault or from formation of a new fracture that is near the direction of maximum shear stress. The behavior of a geomechanical system as it approaches instability, or catastrophic failure, has been described in earlier work by the author [Dubrovskiy, 1984; Dubrovskiy and Sergeev, 2004] as a "short-term universal precursor" theorem. According to this theorem, if the system has the state of the unstable equilibrium at some set of the critical parameters describing it and this set separates areas of the parameters values relevant to a stable state and unstable state of the system then in stable parameters area external load would cause eigen oscillation of the system with frequencies, which will tend to zero if the system approaches unstable equilibrium at the finite critical wavelengths. Thus prior to an earthquake, one should be able to observe slow oscillations with a frequency that tends to zero as the earthquake approaches. In a system where friction is velocity and displacement dependent, the predicted perturbing oscillations are fault-zone trapped waves. They are propagating along fault (their amplitude attenuates exponentially perpendicular to the fault) and perturbing fault slip speed [Li, Leary, Aki, Malin, 1990]. If trapped waves amplitude is growing with time then the process of the fault slip with uniform speed became unstable and slip instability takes place according to principle of the linear instability. Physically it means that energy is pumping from basic state of the uniform fault slip speed to the trapped waves as the disturbance of this state. The dispersion relation of the trapped waves resembles the well known Rayleigh wave equation; however, the right-hand side of the equation is not zero but a term that depends on friction and wave number [Dubrovskiy and Dieterich, 1990]. At the limit of zero frequency, the trapped waves dispersion equation have solution for some critical wave length only if the friction coefficient has an inverse dependence on displacement, i.e. then the condition of the universal precursor theorem is fulfilled and decreasing of trapped wave frequency (and thereby phase velocity) will be short term precursors of the catastrophic slip instability along fault (earthquake). Such an inverse dependence is known as "friction memory" and means that during slip the opposing fault surfaces become smoother. The value of the inverse dependence on displacement determines some characteristic wave length and consequently the locked and slipping parts of the fault surface will appear. These trapped waves are "short-term" precursors to failure. To look for "middle-term" precursors, we turn to the phenomenon of creep, or plastic behavior, that is observed in the laboratory or in nature prior to failure. Linearizing and solving the linearized equations of ideal plasticity, we find that kx/ky? cx/cy=tan? (or -cot?), where kx and ky are x and y components of the wave vector k and cx and cy are x and y components of the phase velocity c, ? is the angle between the direction of maximum shear stress (actually fault direction in the case of a new fracture) and x axis. Thus, one could observe the onset of seismic wave anisotropy as a "middle-term" precursor to an earthquake. The time behavior of this "middle-term" precursor can be obtained by solving the full time depended plasticity equations. I am grateful to Gary Fuis (USGS) for useful discussions. This work was supported by Russian Foundation for Basic Research, project no. 03-05-64087.

Dubrovskiy, V.



The Search for Precursor Redline Auroral Events  

NASA Astrophysics Data System (ADS)

A popular theory of geomagnetic substorms postulates that substorms begin in the downtail region of the magnetosphere and propagate Earthward. This should result in a visible auroral precursor; however, observations have not shown such formations. This poster presents the results of our project to examine the little-studied redline data in search of these early-cycle auroral phenomena. We reviewed daily ground-based redline auroral observations for relevant months of 2008-2013 using software developed in IDL and created an event database with the observation stations, onset timestamp, available satellites, and notes. After narrowing the initial list of nearly 350 events to the best 5, we analyzed the redline events alongside white light and green light observations from the same stations, as well as in situ measurements from THEMIS and geomagnetic readings from ground-based stations. Preliminary results from 36 suspected cases and 5 confirmed cases show some instances of clear redline formations that precede visual onsets. These phenomena form above the equatorward auroral arc, descend over several minutes, and then appear to trigger onset within minutes of reaching the arc boundary. We also found evidence that these precursors are created by earthward plasma flows. This research helps answer the long-standing question of why there has been no visible precursor, despite strong evidence of pre-onset earthward flows. It is one of the first ventures into the lower spectra of the aurora, opening the door for future work on the longer-lasting, lower-energy, and more sensitive red wavelengths.

Sobel, E. I.; Kepko, L.; Angelopoulos, V.; Donovan, E.; Spanswick, E.



Neutron-powered precursors of kilonovae  

NASA Astrophysics Data System (ADS)

The merger of binary neutron stars (NSs) ejects a small quantity of neutron-rich matter, the radioactive decay of which powers a day to week long thermal transient known as a kilonova. Most of the ejecta remains sufficiently dense during its expansion that all neutrons are captured into nuclei during the r-process. However, recent general relativistic merger simulations by Bauswein and collaborators show that a small fraction of the ejected mass (a few per cent, or ˜10-4 M?) expands sufficiently rapidly for most neutrons to avoid capture. This matter originates from the shocked-heated interface between the merging NSs. Here, we show that the ?-decay of these free neutrons in the outermost ejecta powers a `precursor' to the main kilonova emission, which peaks on a time-scale of ˜ few hours following merger at U-band magnitude ˜22 (for an assumed distance of 200 Mpc). The high luminosity and blue colours of the neutron precursor render it a potentially important counterpart to the gravitational wave source, that may encode valuable information on the properties of the merging binary (e.g. NS-NS versus NS-black hole) and the NS equation of state. Future work is necessary to assess the robustness of the fast-moving ejecta and the survival of free neutrons in the face of neutrino absorptions, although the precursor properties are robust to a moderate amount of leptonization. Our results provide additional motivation for short latency gravitational wave triggers and rapid follow-up searches with sensitive ground-based telescopes.

Metzger, Brian D.; Bauswein, Andreas; Goriely, Stephane; Kasen, Daniel



Ballooning instability precursors to high {beta} disruptions  

SciTech Connect

Strongly ballooning modes have been found as precursors to high {beta} disruptions on TFTR. The modes are typically localized to a region spanning about 60{degree} in the toroidal direction. The toroidal localization is associated with lower frequency, global Magneto-Hydro-Dynamic (MHD) activity, typically an ideal n = 1 kink mode. They have moderate to high frequency (f = 10--20 f{sub rot}), implying toroidal mode numbers in the range n = 10--20. The growth rates for the modes are large, of order 10{sup 4}/sec.

Fredrickson, E.D.; McGuire, K.M.; Chang, Z.Y. [and others



The Mars 2001 Athena Precursor Experiment (APEX)  

NASA Technical Reports Server (NTRS)

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.

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



Gamma butyrolactone (GBL) and gamma valerolactone (GVL): similarities and differences in their effects on the acoustic startle reflex and the conditioned enhancement of startle in the rat.  


Gamma butyrolactone (GBL) is metabolized to gamma hydroxybutyrate (GHB) in the body. GHB is a DEA Schedule 1 compound; GBL is a DEA List 1 chemical. Gamma valerolactone (GVL) is the 4-methyl analog of GBL; GVL is metabolized to 4-methyl-GHB; GVL is NOT metabolized to GBL or GHB. The effects of GBL (18.75-150 mg/kg), GVL (200-1600 mg/kg) or vehicle on the acoustic startle reflex (ASR), and the classically-conditioned enhancement of startle, the Startle Anticipated Potentiation of Startle (SAPS) response were studied in male rats. Both compounds produced a dose-dependent reduction of ASR, with GBL 5-7 times more potent than GVL. In contrast, GBL treatment significantly reduced SAPS at doses that exerted only moderate effects on ASR, whereas GVL exerted little or no effect on the SAPS, except at doses that produced pronounced reductions in Noise Alone ASR. In a second experiment, rats were tested for Noise Alone ASR behavior following treatment with a single mid-range dose of GBL (75 mg/kg), GVL (400mg/kg) or vehicle; immediately following startle testing the animals were sacrificed and their brains and blood were collected for determination of GHB, 4-methyl-GHB, GBL and GVL. GHB was found in measurable concentrations in all of the blood specimens and 6 (of 8) of the brain specimens from the GBL-treated subjects. 4-Methyl-GHB was found in measurable concentrations in all of the blood and brain specimens of the GVL-treated subjects; the change in startle amplitude was inversely correlated to the brain concentrations of these compounds. These findings confirm the differences in the metabolic fate of GBL and GVL as pro-drugs for the formation of GHB and 4-methyl-GHB, respectively. Moreover, the dissimilarity in effect profile for GBL and GVL on ASR versus SAPS behaviors suggests that different receptor(s) may be involved in mediating these behavioral effects. PMID:22349589

Marinetti, Laureen J; Leavell, Bonita J; Jones, Calleen M; Hepler, Bradford R; Isenschmid, Daniel S; Commissaris, Randall L



Cellular Precursors of the Coronary Arteries  

PubMed Central

Coronary vessels develop from a primary vascular network that differentiates in the subepicardium through a process of vasculogenesis, that is, self-assembly of mesenchymal vascular progenitors. Further growth of the subepicardial vascular plexus through a complex process of angiogenesis, vascular remodeling, and arterialization of specific branches gives rise to the definitive coronary system. This report is intended to summarize current knowledge on the origin of the coronary vascular progenitors and to provide new insights suggested by recent findings. It has been established that the mesenchymal precursors of the vascular smooth muscle cells and the adventitial fibroblasts originate from an epithelial-mesenchymal transformation of the epicardial mesothelium. We report herein experimental evidence that the precursors of the coronary endothelium are also epicardium-derived cells (EPDCs). The evidence shown includes co-localization of mesothelial and endothelial molecular markers as well as cell lineage studies performed through direct labeling of the epicardial cells. If this proposal is confirmed, the early EPDCs might be found to have a competence similar to that shown by the recently discovered bipotential vascular progenitor cells, which are able to differentiate into endothelium or smooth muscle depending on their exposure to VEGF or PDGF-BB. It is conceivable that the earliest EPDCs differentiate into endothelial cells in response to myocardially secreted VEGF, while subsequent EPDCs, recruited by the nascent capillaries via PDGFR? signaling, differentiate into pericytes and smooth muscle cells. (Tex Heart Inst J 2002;29:243–9) PMID:12484607

Muñoz-Chápuli, Ramón; González-Iriarte, Mauricio; Carmona, Rita; Atencia, Gerardo; Macías, David; Pérez-Pomares, José María



Isolation of mouse thymic dendritic cell precursors.  


Dendritic cells (DC) are efficient antigen-presenting cells. Their ability to present antigens via MHC class I and MHC class II molecules to T cells allows them not only to initiate an immune response to exogenous pathogens but also to induce immune tolerance to self-antigens. Thymic DC play important roles in the establishment of central immune tolerance by presenting self-antigens to developing thymocytes and subsequently deleting the self-reactive thymocytes and inducing naturally occurring regulatory T cells. DC in the thymus are comprised of plasmacytoid DC (pDC) and conventional DC (cDC) populations. The cDC can be divided into two populations based on the expression of CD8 alpha and Sirp alpha: CD8 alpha(+)Sirp alpha(l) degrees (approximately 70%) and CD8 alpha(l) degrees Sirp alpha(+) (approximately 30%). The CD8 alpha(+)Sirp alpha(l) degrees cDC are generated in the thymus by the earliest intrathymic oligo-potent progenitors that are also precursors for T-lineage cells and natural killer cells (NK cells). Whereas the CD8 alpha(l) degrees Sirp alpha(+)cDC and pDC are migratory DC and originate mainly from peripheral blood. The ability to isolate and purify the earliest intrathymic precursors allows us to generate thymic cDC in culture or in vivo upon intrathymic or intravenous injections. These experimental systems are crucial for studying the development and functions of thymic DC. PMID:19941119

Wu, Li; D'Amico, Angela



Solar-cycle precursors and predictions  

NASA Astrophysics Data System (ADS)

The sunspot number data during the past 400 years indicates that both the profile and the amplitude of the solar cycle have large variations. Some precursors of the solar cycle were identified aiming to predict the solar cycle. The polar field and the geomagnetic index are two precursors which are received the most attention. The geomagnetic variations during the solar minima are potentially caused by the solar polar field by the connection of the solar open flux. The robust prediction skill of the polar field indicates that the memory of the dynamo process is less than 11 yrs based on the frame of the Babcock-Leighton flux transport dynamo. One possible reason to get the short magnetic memory is the high magnetic diffusivity in the convective zone. Our recent studies show that the radial downward pumping is another possible reason. Based upon the mechanism, we well simulate the cycle irregularities during RGO time period. This opens the possibility to set up a standard dynamo based model to predict the solar cycle. In the end, the no correlation between the polar field and the preceding cycle strength due to two nonlinearities involved in the sunspot emergence will be stressed.

Jiang, Jie



Solar-cycle precursors and predictions  

E-print Network

The sunspot number data during the past 400 years indicates that both the profile and the amplitude of the solar cycle have large variations. Some precursors of the solar cycle were identified aiming to predict the solar cycle. The polar field and the geomagnetic index are two precursors which are received the most attention. The geomagnetic variations during the solar minima are potentially caused by the solar polar field by the connection of the solar open flux. The robust prediction skill of the polar field indicates that the memory of the dynamo process is less than 11 yrs within the framework of the Babcock-Leighton flux transport dynamo. One possible reason to get the short magnetic memory is the high magnetic diffusivity in the convective zone. Our recent studies show that the radial downward pumping is another possible reason. Based upon the mechanism, we well simulate the cycle irregularities during RGO time period. This opens the possibility to set up a standard dynamo based model to predict the sol...

Jiang, Jie



Wenchuan Earthquake Ionospheric Precursors: Modeling and Experiment  

NASA Astrophysics Data System (ADS)

Early it was shown, that for strong middle-latitude earthquakes the effects in Total Electron Content (TEC) and in critical frequency of F2-layer (foF2) look like local changes in electron concentration which maxima are located in immediate proximity from epicenter area. Pre-cursory effects of strong near-equatorial earthquakes might be in the form of deepening and widening of electron concentration minimum over the magnetic equator and displacement of equatorial ionization anomaly crests. The problems of physical explanation of possible forma-tion mechanisms of the seismo-ionospheric effects are under discussion now. In Namgaladze et al., 2009 it has been come out with the assumption, that the most probable formation mech-anism of TEC disturbed areas, observable prior strong earthquakes, is the vertical transport of the F2-region ionospheric plasma under the zonal electric field action. The geomagnetic conjugacy of the earthquake ionospheric precursors and effects in equatorial anomaly which development is controlled by zonal electric field are strong arguments in favor of this hypoth-esis. Besides, the analysis of model calculation results with use of the Global Self-consistent Model of the Thermosphere, Ionosphere, Protonosphere (GSM TIP) in Namgaladze et al., 2009 testifies in favor of this hypothesis. There is a question how such electric fields can arise in the ionosphere prior to earthquakes? Now it is not answer to this question. Therefore, for understanding of formation mechanisms of earthquake ionospheric precursors it is necessary to understand the physics of lithosphere-atmosphere-ionosphere coupling prior to earthquake. Many researchers tried to solve this problem. However, until now there is not common opinion concerning to the lithosphere-atmosphere-ionosphere coupling prior to earthquake. Some ba-sic hypotheses for the explanation of this mechanism have been offered: the Internal Gravity Waves (IGWs) of seismogenic origin with the period 1-3 hours, the IGWs with the period from several minutes up to tens minutes, the seismogenic electric field with amplitude from units up to tens mV/m, the abnormal electromagnetic fields and emissions. However, the appearance of local large-scale seismo-ionospheric anomalies in TEC and foF2 it is possible to explain only by two of the mentioned mechanisms: an atmospheric electric field and/or small-scale IGWs. In this study, we present the numerical calculation results for reproduction of observed changes in the ionosphere prior to strong Wenchuan earthquake. This earthquake has been fixed on 12 May 2008. The geomagnetic activity indices for the period on 1-13 May were low. The calcu-lations of Wenchuan earthquake ionospheric precursors were carried out with use of the GSM TIP model. In calculations, the small-scale IGWs and/or the penetration of vertical electric field are considered as the formation mechanisms of earthquake ionospheric precursors. It was carried out the comparison of calculation results with experimental data of TEC and foF2 at various stations, located in China and nearby areas. The obtained results confirm the proposed mechanisms of seismo-ionospheric effect formation by small-scale IGWs and the penetration of the seismogenic vertical electric field from the atmosphere into the ionosphere. References Namgaladze A.A., Klimenko M.V., Klimenko V.V. and Zakharenkova I.E. Physical Mechanism and Mathematical Simulation of Ionosphere Earthquake Precursors Observed in Total Electron Content. Geomagnetism and Aeronomy, 2009, Vol. 49, 252-262.

Klimenko, Maxim; Klimenko, Vladimir; Zhao, Biqiang; Pulinets, Sergej; Zakharenkova, Irina; Bryukhanov, Valerij


Study of tectonic earthquake precursors by geodetic methods  

SciTech Connect

Deformations of the Earth's surface which can be revealed by geodetic methods are among the most reliable earthquake precursors. A brief list is presented of geodetic leveling methods which have revealed the precursors of several earthquakes. To confirm the accuracy of determination of precursors of earthquakes based on the results of repeated leveling in epicenter zones and observations at Alma-Ata, the magnitudes of 7 earthquakes which occurred in northern Tien Shan during measurement of tectonic precursors were calculated and compared to valves based on seismologic measurements. The agreement found is satisfactory. A scientifically well-founded program of tectonic movements by geodetic methods in the northern Tien Shan has thus established the presence of tectonic precursors of earthquakes, determined the distances over which they are manifested and shown the possiblity of using the results of geodetic measurements in combiantion with geophysical and seismologic data to estimate the possible time of appearance of earthquake precursors.

Sigalov, V.M.



Filler/ Polycarbosilane Systems as CMC Matrix Precursors  

NASA Technical Reports Server (NTRS)

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.

Hurwitz, Frances I.



Silsesquioxanes as precursors to ceramic composites  

NASA Technical Reports Server (NTRS)

Silsesquioxanes having the general structure RSiO(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 source 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.

Hurwitz, F. I.; Hyatt, L.; Gorecki, J.; D'Amore, L.



Silsesquioxanes as precursors to ceramic composites  

NASA Technical Reports Server (NTRS)

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.

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



Design of Aerosol Coating Reactors: Precursor Injection  

PubMed Central

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

Buesser, Beat; Pratsinis, Sotiris E.



Polymer precursors for ceramic matrix composites  

NASA Technical Reports Server (NTRS)

The synthesis and characterization of a polycyclohexasilane is reported. Because of its cyclic structure, it is anticipated that this polymer might serve as a precursor to SIC having a high char yield with little rearrangement to form small, volatile cyclic silanes, and, as such, would be of interest as a precursor to SiC composite matrices and fibers, or as a binder in ceramic processing. Several approaches to the synthesis of a bifunctional cyclic monomer were attempted; the most successful of these was metal coupling of PhMeSiCl2 and Me2SiCl2. The procedure gives six-membered ring compounds with all degrees of phenyl substitution, from none to hexaphenyl. The compounds with from 0-2 groups were isolated and characterized. The fraction with degree of phenyl substitution equal to 2, a mixture of cis and trans 1,2-; 1,3-; and 1,4 isomers, was isolated in 32 percent yield. Pure 1,4 diphenyldecamethylcyclohexasilane was isolated from the mixed diphenyl compounds and characterized. Diphenyldecamethylcyclohexasilanes were dephenylated to dichlorodecamethylcyclohexasilanes by treating with H2SO4.NH4Cl in benzene. The latter were purified and polymerized by reacting with sodium in toluene. The polymers were characterized by HPGPC, elemental analysis, proton NMR, and IR. Thermogravimetric analyses were carried out on the polymers. As the yield of residual SiC was low, polymers were heat treated to increase the residual char yield. As high as 51.52 percent residual char yield was obtained in one case.

Litt, M. H.; Kumar, K.



DHEA - a precursor of ER? ligands.  


What is DHEA and why is there so much public interest in this steroid which has been touted as the fountain of youth and is supposed to have all kinds of health benefits? Endocrinologists have been fascinated with DHEA for a long time because of its high production in the fetal adrenals and its continued high levels until the 7th decade of life. Yet there is still little agreement about its physiological functions. In its simplest terms endocrinology is the communication between at least three organs: one sends a message, one releases a hormone into the blood in response to the message and one responds to the hormone. DHEA is produced by a specific zone of the adrenal cortex, the zona reticularis, whose sole function is to produce this steroid. Glucocorticoids and mineralocorticoids which are C21 steroids are produced in two other zones of the adrenal cortex called the zona fasicularis and the zona glomerulosa, respectively. Being C21 steroids, they cannot be synthesized from DHEA which is a C19 steroid. To date there is no known hormone which specifically stimulates the zona reticularis and there is no known specific receptor for DHEA. Thus DHEA does not qualify as a hormone. DHEA could have autocrine or paracrine effects but, so far, there is no known effect of DHEA on either the cells of the zona glomerulosa or the zona fasicularis. Of course DHEA could have functions as a local precursor of androgens or estrogens and many studies have reported on the beneficial effects of transdermal or transvaginal administration of DHEA in postmenopausal women. This review will consider two of the potential functions of DHEA as a precursor of estrogen receptor beta (ER?) ligands. PMID:25125389

Warner, Margaret; Gustafsson, Jan-Ake



Observations of Precursor Breakdown Prior to Intracloud Lightning Discharges  

NASA Astrophysics Data System (ADS)

Using the New Mexico Tech VHF Lightning Mapping Array (LMA) we have detected weak precursor discharges occurring up to a few tens of seconds before the initiation of normal polarity intracloud (IC) lightning discharges. With the very sensitive LMA installed at White Sands Missile Range (WSMR) in south central New Mexico, we observe low-power VHF precursor events in about 10% of lightning discharges. Most of the precursors occur within horizontal distances of about 200 meters of the locations of the initial LMA sources observed in the subsequent discharges, with altitudes about the same as the altitudes of the initial LMA sources. Most precursors consist of a single LMA source, indicating that the duration of the RF emission is less than the 80 ?s time window of the WSMR LMA. Occasionally, a given precursor event lasts for up to 400 ?s. For most discharges with precursors, only one precursor is observed, occurring anywhere from a few hundred milliseconds to 30 seconds before the discharge. For some flashes, more precursors are observed, several seconds apart. In a few cases, some of the precursor sources are several kilometers from the initial LMA source. In these cases, the leader channels of the ensuing discharge propagate from the flash initiation point to the horizontal locations of the distant precursors. The precursors apparently occur in the regions of the highest pre-discharge fields in the cell, indicating high field regions before the lightning discharge. The precursors are observed only at altitudes of about 8 to 10 km, corresponding to the region between the mid-level negative and upper positive storm charges. We have not observed precursors at altitudes in the 5 to 7 km range, corresponding to the region below the mid-level negative charge where CG discharges are initiated. The altitude dependence of the precursors may result from the fact that breakdown is easier to initiate at lower pressures. Because of RF emission restrictions at WSMR, the background noise levels are about a factor of ten lower than other LMA arrays. We have observed precursors with less sensitive LMAs. In particular, we observed numerous IC precursors in an inverted polarity storm during the Severe Thunderstorm Electrification/Precipitation Study (STEPS 2000) project in western Kansas and eastern Colorado. Inverted polarity storms during STEPS and in Oklahoma were often observed to produce steady streams of temporally- and spatially-isolated single point discharges similar to precursors at the higher altitudes of the upper negative charge, and at even higher altitudes (up to 17-18 km) during convective surges in the storms. These observations also indicate that short duration precursor-type breakdown is easier to initiate at higher altitudes. If IC precursors are initiated by the same process that initiates the IC discharges, the abundance of precursors argue against cosmic ray induced air showers as the initiation mechanism which requires cosmic rays with energies of at least 1016 eV. The flux of such high energy cosmic rays is too low to initiate several precursors near the lightning initiation location within a period of a few tens of seconds. We thank the WSMR Meteorology Branch for data used for this work.

Rison, W.; Krehbiel, P. R.; Thomas, R. J.; Brown, M. F.



Can the irradiated brain be salvaged by oligodendrocyte precursor transplantation?  


Radiotherapy is a mainstay of brain cancer treatment, but it causes significant complications. In this issue of Cell Stem Cell, Piao et al. (2015) derive oligodendrocyte precursors from human embryonic stem cells and show that engrafted cells replenish depleted precursor numbers, generate new myelin, and reverse behavioral defects in irradiated rats. PMID:25658367

Harrisingh, Marie C; Ffrench-Constant, Charles



Precursor Studies in an Electromagnetically Driven Shock Tube  

Microsoft Academic Search

Precursor waves have been studied in an electromagnetic shock tube of the T configuration. The precursor velocity, electron density, and current content were determined over a pressure range of 1 to 1000? Hg, for electrode discharge voltages of 3 to 17 kV in hydrogen and argon. A longitudinal nanosecond microwave technique was used in conjunction with a semi-infinite microwave cavity

M. J. Lubin; E. L. Resler



Precursors to Aggression Are Evident by 6 Months of Age  

ERIC Educational Resources Information Center

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…

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



An Evaluation of Strengthening Precursors to Increase Preschooler Compliance  

ERIC Educational Resources Information Center

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…

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



Effects of rhythmic precursors on perception of stress/syllabicity  

NASA Astrophysics Data System (ADS)

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.

Stilp, Christian E.; Kluender, Keith R.



Topographical and Functional Properties of Precursors to Severe Problem Behavior  

ERIC Educational Resources Information Center

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…

Fahmie, Tara A.; Iwata, Brian A.



Comparative Proteomics Indicates That Biosynthesis of Pectic Precursors Is Important  

E-print Network

primary cell walls contained significantly higher amounts of pectin, whereas more hemicellulose was found, or UDP-D-glucuronic acid, all of which were readily incorporated into the pectin fraction of cell wall a specific pectin precursor to the growth medium. When two pectin precursors, produced by either UDP-4- keto

Western, Tamara L.


Precursor Exploration Missions in Kelly Lake, British Columbia MARSLIFE project  

Microsoft Academic Search

Precursor missions are an integral step in coordinated exploration between unmanned and manned systems both for terrestrial and astrobiology applications. Testing and developing the protocols for efficient, safe, and meaningful precursor missions is a key step in readiness for space exploration and is integral to the new MARSLIFE analogue research project. Here we present first-year field results from the use

A. C. Trembanis; J. Gutsche; S. H. Nebel



Endogenous Nkx2.2+ oligodendrocyte precursor cells fail  

E-print Network

Endogenous Nkx2.2+ /Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated of endogenous oligodendrocyte precursor cells (OPCs) following ethidium bromide (EB)-induced demyelination proliferative NG2+ cells within the lesion was observed, none of which expressed the oligodendrocyte lineage

Harkema, Susan


Precursor film controlled wetting of Pb on Cu.  


Wetting in a system where the kinetics of drop spreading are controlled by the rate of formation of a precursor film is modeled for the first time at the atomistic scale. Molecular dynamics simulations of Pb(l) wetting Cu(111) and Cu(100) show that a precursor film of atomic thickness evolves and spreads diffusively. This precursor film spreads significantly faster on Cu(111) than on Cu(100). For Cu(100), the kinetics of drop spreading are dramatically decreased by slow advancement of the precursor film. Slow precursor film kinetics on Cu(100) are partly due to the formation of a surface alloy at the solid-liquid interface which does not occur on Cu(111). PMID:14683202

Webb, Edmund B; Grest, Gary S; Heine, David R



A hydrophilic interaction liquid chromatography electrospray tandem mass spectrometry method for the simultaneous determination of ?-hydroxybutyrate and its precursors in forensic whole blood.  


A liquid-chromatography-tandem-mass-spectrometry method using pneumatically assisted electrospray ionisation (LC-ESI-MS/MS) was developed for the simultaneous determination of ?-hydroxybutyric acid (GHB), ?-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in human ante-mortem and post-mortem whole blood. The blood proteins were precipitated using a mixture of methanol and acetonitrile, and the extract was cleaned-up by passage through a polymeric strong cation exchange sorbent. Separation of the analytes and their structural isomers was obtained using a column with a zwitterionic stationary phase. Matrix-matched calibrants, combined with isotope dilution, were used for quantitative analysis. GHB was determined in both positive and negative ion modes. The relative intra-laboratory reproducibility standard deviations were better than 10% and 6% for blood samples at concentrations of 2 mg/L and 20-150 mg/L, respectively. The mean true extraction recoveries were 80% for GHB and greater than 90% for GBL and 1,4-BD at concentration levels of 20-50 mg/L. The limits of detection were approximately 0.5 mg/L for GHB and GBL, and 0.02 mg/L for 1,4-BD in ante-mortem blood. The corresponding lower limits of quantification were less than 1 mg/L for GHB and GBL, and less than 0.1 mg/L for 1,4-BD. GBL was unstable in whole blood freshly preserved with a sodium fluoride oxalate mixture, but the stability could be improved significantly by preservation with a sodium fluoride citrate EDTA mixture. PMID:22917943

Sørensen, Lambert K; Hasselstrøm, Jørgen B



Bacterial Cellular Materials as Precursors of Chloroform  

NASA Astrophysics Data System (ADS)

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 ?g-chloroform /mg-C were generated during the bacterial chlorination, in similar order of magnitude to that generated by humic acid (previously reported as 78 ?g-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.

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



Amyloid ? precursor protein regulates male sexual behavior  

PubMed Central

Sexual behavior is variable between individuals, ranging from celibacy to sexual addictions. Within normal populations of individual men, ranging from young to middle aged, testosterone levels do not correlate with libido. To study the genetic mechanisms that contribute to individual differences in male sexual behavior, we used hybrid B6D2F1 male mice, which are a cross between two common inbred strains (C57BL/6J and DBA/2J). Unlike most laboratory rodent species in which male sexual behavior is highly dependent upon gonadal steroids, sexual behavior in a large proportion of these hybrid male mice after castration is independent of gonadal steroid hormones and their receptors; thus, we have the ability to discover novel genes involved in this behavior. Gene expression arrays, validation of gene candidates, and transgenic mice that over-express one of the genes of interest were utilized to reveal genes involved in maintenance of male sexual behavior. Several genes related to neuroprotection and neurodegeneration were differentially expressed in the hypothalamus of males that continued to mate after castration. Male mice over-expressing the human form of one of these candidate genes, amyloid beta precursor protein (APP), displayed enhanced sexual behavior prior to castration and maintained sexual activity for a longer duration after castration as compared with controls. Our results reveal a novel and unexpected relationship between APP and male sexual behavior. We speculate that declining APP during normal aging in males may contribute to the loss of sexual function. PMID:20668181

Park, Jin Ho; Bonthius, Paul; Tsai, Houng-Wei; Bekiranov, Stefan; Rissman, Emilie F.



Identification, selection, and enrichment of cardiomyocyte precursors.  


The large-scale production of cardiomyocytes is a key step in the development of cell therapy and tissue engineering to treat cardiovascular diseases, particularly those caused by ischemia. The main objective of this study was to establish a procedure for the efficient production of cardiomyocytes by reprogramming mesenchymal stem cells from adipose tissue. First, lentiviral vectors expressing neoR and GFP under the control of promoters expressed specifically during cardiomyogenesis were constructed to monitor cell reprogramming into precardiomyocytes and to select cells for amplification and characterization. Cellular reprogramming was performed using 5'-azacytidine followed by electroporation with plasmid pOKS2a, which expressed Oct4, Sox2, and Klf4. Under these conditions, GFP expression began only after transfection with pOKS2a, and less than 0.015% of cells were GFP(+). These GFP(+) cells were selected for G418 resistance to find molecular markers of cardiomyocytes by RT-PCR and immunocytochemistry. Both genetic and protein markers of cardiomyocytes were present in the selected cells, with some variations among them. Cell doubling time did not change after selection. Together, these results indicate that enrichment with vectors expressing GFP and neoR under cardiomyocyte-specific promoters can produce large numbers of cardiomyocyte precursors (CMPs), which can then be differentiated terminally for cell therapy and tissue engineering. PMID:23853770

Zanetti, Bianca Ferrarini; Gomes, Walter José; Han, Sang Won



A fission-powered interstellar precursor mission  

SciTech Connect

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.}

Lipinski, Ronald J.; Lenard, Roger X.; Wright, Steven A. [Sandia National Laboratories, MS-1146, P.O. Box 5800, Albuquerque, New Mexico 87185 (United States)] West, John L. [Jet Propulsion Laboratory, MS-301-490, Pasadena, California 91109-8099 (United States)



Robotic Precursor Missions for Mars Habitats  

NASA Technical Reports Server (NTRS)

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.

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



Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers  

PubMed Central

Rationale Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects. Objectives This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. Materials and methods Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. Conclusions Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers. PMID:19543883

Carter, Lawrence P.; Griffiths, Roland R.; Mintzer, Miriam Z.



Clustering chlorine reactivity of haloacetic acid precursors in inland lakes.  


Dissolved organic matter (DOM) represents the major pool of organic precursors for harmful disinfection byproducts, such as haloacetic acids (HAAs), formed during drinking water chlorination, but much of it remains molecularly uncharacterized. Knowledge of model precursors is thus a prerequisite for understanding the more complex whole water DOM. The utility of HAA formation potential data from model DOM precursors, however, is limited due to the lack of comparability to water samples. In this study, the formation kinetics of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two predominant HAA species, were delineated upon chlorination of seventeen model DOM precursors and sixty-eight inland lake water samples collected from the Upper Midwest region of the United States. Of particular interest was the finding that the DCAA and TCAA formation rate constants could be grouped into four statistically distinct clusters reflecting the core structural features of model DOM precursors (i.e., non-?-diketone aliphatics, ?-diketone aliphatics, non-?-diketone phenolics, and ?-diketone phenolics). A comparative approach built upon hierarchical cluster analysis was developed to gain further insight into the chlorine reactivity patterns of HAA precursors in inland lake waters as defined by the relative proximity to four model precursor clusters. This work highlights the potential for implementing an integrated kinetic-clustering approach to constrain the chlorine reactivity of DOM in source waters. PMID:24299068

Zeng, Teng; Arnold, William A



Photospheric Radius Expansion in Superburst Precursors from Neutron Stars  

NASA Astrophysics Data System (ADS)

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.

Keek, L.



Amine precursor uptake and decarboxylation: significance for processing of the rat gastrin precursor.  

PubMed Central

1. Conversion of prohormone precursors to smaller active products occurs in secretory granules, which also have the capacity to concentrate biogenic amines. We have examined how processing of the gastrin precursor, progastrin, in rat antral mucosa is influenced by modulation of the biogenic amine content of secretory granules. 2. Newly synthesized progastrin-derived peptides in rat antral mucosa were labelled in vitro with 35SO4(2-) using a pulse-chase protocol and detected after immunoprecipitation by HPLC with on-line liquid scintillation counting. Secretory granule morphology was examined by electron microscopy. The effects of experimentally manipulating secretory granule pH and amine content were examined. 3. The dopamine precursor L-beta-3,4-dihydroxyphenylalanine (L-DOPA) inhibited cleavage of 35S-labelled thirty-four amino acid amidated gastrin, i.e. [35S]G34, and of [35S]G34 with COOH-terminal glycine, i.e. [35S]G34-Gly, at a pair of lysine residues, but did not influence cleavage of progastrin at pairs of arginine residues. The effect of L-DOPA was reversed by reserpine, which inhibits the amine-proton exchangers VMAT1 and VMAT2, and by carbidopa, which inhibits aromatic L-amino acid decarboxylase. 4. Treatments that raise intragranular pH, e.g. the weak base chloroquine, the ionophore monensin and the vacuolar proton pump inhibitor bafilomycin A1, had similar effects to L-DOPA. 5. Electron microscopical studies showed that the electron-dense aggregrates in gastrin cell secretory granules were lost after inhibition of the vacuolar proton pump. Treatment with L-DOPA produced reserpine-sensitive dissipation of the electron-dense aggregates, compatible with the idea that increased amine delivery raised intragranular pH. 6. The data suggest that the processes of amine precursor uptake, decarboxylation and sequestration in secretory granules are associated with selective modulation of progastrin cleavage, possibly by raising intragranular pH and thereby inhibiting pH-sensitive prohormone convertases. Images Figure 8 PMID:9192308

Voronina, S; Henry, J; Vaillant, C; Dockray, G J; Varro, A



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

PubMed Central

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

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




SciTech Connect

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.




Optimality properties of a proposed precursor to the genetic code  

NASA Astrophysics Data System (ADS)

We calculate the optimality score of a doublet precursor to the canonical genetic code with respect to mitigating the effects of point mutations and compare our results to corresponding ones for the canonical genetic code. We find that the proposed precursor is much less optimal than that of the canonical code. Our results render unlikely the notion that the doublet precursor was an intermediate state in the evolution of the canonical genetic code. These findings support the notion that code optimality reflects evolutionary dynamics, and that if such a doublet code originally had a biochemical significance, it arose before the emergence of translation.

Butler, Thomas; Goldenfeld, Nigel



An evaluation of strengthening precursors to increase preschooler compliance.  


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 contact with, and saying "yes" to the instructor. High levels of precursors occurred during treatment, and increases in compliance also were observed, even though the consequences for compliance and noncompliance did not change. PMID:22403455

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



Schwann Cell-Like Differentiation by Adult Oligodendrocyte Precursor Cells Following Engraftment  

E-print Network

Schwann Cell-Like Differentiation by Adult Oligodendrocyte Precursor Cells Following Engraftment demyelination; remyelination; noggin; adult oligodendrocyte precursor cell; astrocyte; spinal cord ABSTRACT spinal-cord- derived oligodendrocyte precursor cells (adult OPCs). In the present study, we demonstrate

Harkema, Susan


Effects of monocarboxylate transporter inhibition on the oral toxicokinetics/toxicodynamics of ?-hydroxybutyrate and ?-butyrolactone.  


Respiratory depression and death secondary to respiratory arrest have occurred after oral overdoses of ?-hydroxybutyrate (GHB) and its precursor ?-butyrolactone (GBL). GHB is a substrate for monocarboxylate transporters (MCTs), and increasing GHB renal clearance or decreasing GHB absorption via MCT inhibition represents a potential treatment strategy for GHB/GBL overdose. In these studies, GHB and GBL were administered in doses of 1.92, 5.77, and 14.4 mmol/kg orally with and without MCT inhibition to determine effects of this treatment strategy on the oral toxicokinetics and toxicodynamics of GHB and GBL. The competitive MCT inhibitor l-lactate was administered by intravenous infusion starting 1 hour after GHB and GBL administration. Oral administration of l-lactate and the MCT inhibitor luteolin was also evaluated. Respiratory depression was measured using plethysmography. Intravenous l-lactate, but not oral treatments, significantly increased GHB renal and/or oral clearances. At the low dose of GHB and GBL, i.v. l-lactate increased GHB renal clearance. Due to the increased contribution of renal clearance to total clearance at the moderate dose, increased renal clearance translated to an increase in oral clearance. At the highest GHB dose, oral clearance was increased without a significant change in renal clearance. The lack of effect of i.v. l-lactate on renal clearance after a high oral GHB dose suggests possible effects of i.v. l-lactate on MCT-mediated absorption. The resulting increases in oral clearance improved respiratory depression. Intravenous l-lactate also reduced mortality with the high GBL dose. These data indicate i.v. l-lactate represents a potential treatment strategy in oral overdose of GHB and GBL. PMID:23392755

Morse, Bridget L; Morris, Marilyn E



Effects of Monocarboxylate Transporter Inhibition on the Oral Toxicokinetics/Toxicodynamics of ?-Hydroxybutyrate and ?-Butyrolactone  

PubMed Central

Respiratory depression and death secondary to respiratory arrest have occurred after oral overdoses of ?-hydroxybutyrate (GHB) and its precursor ?-butyrolactone (GBL). GHB is a substrate for monocarboxylate transporters (MCTs), and increasing GHB renal clearance or decreasing GHB absorption via MCT inhibition represents a potential treatment strategy for GHB/GBL overdose. In these studies, GHB and GBL were administered in doses of 1.92, 5.77, and 14.4 mmol/kg orally with and without MCT inhibition to determine effects of this treatment strategy on the oral toxicokinetics and toxicodynamics of GHB and GBL. The competitive MCT inhibitor l-lactate was administered by intravenous infusion starting 1 hour after GHB and GBL administration. Oral administration of l-lactate and the MCT inhibitor luteolin was also evaluated. Respiratory depression was measured using plethysmography. Intravenous l-lactate, but not oral treatments, significantly increased GHB renal and/or oral clearances. At the low dose of GHB and GBL, i.v. l-lactate increased GHB renal clearance. Due to the increased contribution of renal clearance to total clearance at the moderate dose, increased renal clearance translated to an increase in oral clearance. At the highest GHB dose, oral clearance was increased without a significant change in renal clearance. The lack of effect of i.v. l-lactate on renal clearance after a high oral GHB dose suggests possible effects of i.v. l-lactate on MCT-mediated absorption. The resulting increases in oral clearance improved respiratory depression. Intravenous l-lactate also reduced mortality with the high GBL dose. These data indicate i.v. l-lactate represents a potential treatment strategy in oral overdose of GHB and GBL. PMID:23392755

Morse, Bridget L.



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

PubMed Central

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

Weir, E



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


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. PMID:12682705

Negrusz, Adam; Gaensslen, R E



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...


Observations of precursor effects in an electromagnetic shock tube  

Microsoft Academic Search

Radiative and electrical precursor effects observed in the expansion tube of an electromagnetic shock tube are described, and several possible mechanisms are discussed. Now at Space Department, Royal Aircraft Est., Farnborough, Hants., England.

D. G. Fearn



Post-treatment of spinnable precursors from petroleum pitch  

SciTech Connect

A spinnable precursor from petroleum pitch is obtained by subjecting a distillable oil removed carbonaceous residue of petroleum origin to solvent extraction and thereafter heat treating the extracted solvent insoluble fraction under reduced pressure.

Dickakian, G.




EPA Science Inventory

An inorganic aerosol equilibrium model is used to investigate the response of inorganic particulate matter (PM) concentrations with respect to the precursor concentrations of sulfuric acid, ammonia, and nitric acid over a range of temperatures and relative humidities. Diagrams...


Transportation Center Seminar........ "The Panama Canal as Precursor"  

E-print Network

Transportation Center Seminar........ "The Panama Canal as Precursor" Aaron J. Gellman Professor of Transportation The Transportation Center & Kellogg School of Management Northwestern University; Advisory:30 pm Location: Transportation Center, Chambers Hall Lower Level, 600 Foster St., Evanston Professor

Bustamante, Fabián E.



EPA Science Inventory

This task involves the development and testing of methods for monitoring ozone and compounds associated with the atmospheric chemistry of ozone production both as precursors and reaction products. Although atmospheric gases are the primary interest, separation of gas and particl...


Precursor composites for oxygen dispersion hardened silver sheathed superconductor composites  


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.

Podtburg, E.R.



Study of Elastic Precursor Decay in ultra fine copper  

NASA Astrophysics Data System (ADS)

Laser interferometer was used to investigate elastic precursor decay in ultra fine copper M1 with the grain size of 0.5 microns. Samples with the thickness of 0.7-12 mm were loaded by shock wave pulse with the pressure of 12GPa. In this particular range of thickness elastic precursor amplitude decays from 1.87 GPa to 1.04 GPa. Ultra fine copper and coarse-grained copper M1 with the grain size of 110 microns were compared with respect to the elastic precursor decay values. It is shown, that elastic precursor amplitude in ultra fine copper samples is in 2 - 3 times higher than in coarse-grained copper samples.

Finyushin, Stanislav; Mikhailov, Anatoliy; Fedorov, Alexey; Nazarov, Dmitriy; Govorunova, Tatiana; Ignatova, Olga



Strong hydrogen bonding between atmospheric nucleation precursors and common organics  

E-print Network

Strong hydrogen bonding between atmospheric nucleation precursors and common organics Alexey B in the atmosphere is poorly understood. In the present Letter, bonding among formic and acetic acids, sulfuric acid

Yu, Fangqun


Are any public-reported earthquake precursors valid?  

NASA Astrophysics Data System (ADS)

This article examines retrospective public-supplied precursor reports statistically, and confirms published hypotheses that some alleged precursors within 100km and within a day prior to the large 1995 Kobe and 1999 Izmit earthquakes, may be valid. The confirmations are mostly at the p<0.001 level of significance. Most significant were alleged meteorological and geophysical precursors, and less often, animal reports. The chi-squared test used, for the first time eliminates the distorting effects of psychological factors on the reports. However it also shows that correct reports are diluted with about the same number which are merely wishful thinking, and obtaining more reliable data would be logistically difficult. Some support is found for another published hypothesis in which other precursors occurred within the ten days prior to the earthquake.

Whitehead, N. E.; Ulusoy, U.; Asahara, H.; Ikeya, M.



Precursor composites for oxygen dispersion hardened silver sheathed superconductor composites  


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.

Podtburg, Eric R. (Natick, MA)



Shape-programmed nanofabrication: understanding the reactivity of dichalcogenide precursors.  


Dialkyl and diaryl dichalcogenides are highly versatile and modular precursors for the synthesis of colloidal chalcogenide nanocrystals. We have used a series of commercially available dichalcogenide precursors to unveil the molecular basis for the outcome of nanocrystal preparations, more specifically, how precursor molecular structure and reactivity affect the final shape and size of II-VI semiconductor nanocrystals. Dichalcogenide precursors used were diallyl, dibenzyl, di-tert-butyl, diisopropyl, diethyl, dimethyl, and diphenyl disulfides and diethyl, dimethyl, and diphenyl diselenides. We find that the presence of two distinctively reactive C-E and E-E bonds makes the chemistry of these precursors much richer and interesting than that of other conventional precursors such as the more common phosphine chalcogenides. Computational studies (DFT) reveal that the dissociation energy of carbon-chalcogen (C-E) bonds in dichalcogenide precursors (R-E-E-R, E=S or Se) increases in the order (R): diallylprecursor reactivity, leading to progressively slower nucleation and higher selectivity for anisotropic growth, all the way from dots to pods to tetrapods. Under identical experimental conditions, we obtain CdS and CdSe nanocrystals with spherical, elongated, or tetrapodal morphology by simply varying the identity and reactivity of the dichalcogenide precursor. Interestingly, we find that precursors with strong C-E and weak E-E bond dissociation energies such as Ph-S-S-Ph serve as a ready source of thiol radicals that appear to stabilize small CdE nuclei, facilitating anisotropic growth. These CdS and CdSe nanocrystals have been characterized using structural and spectroscopic methods. An intimate understanding of how molecular structure affects the chemical reactivity of molecular precursors enables highly predictable and reproducible synthesis of colloidal nanocrystals with specific sizes, shapes, and optoelectronic properties for customized applications. PMID:23517277

Guo, Yijun; Alvarado, Samuel R; Barclay, Joshua D; Vela, Javier



Biological Indicators in Studies of Earthquake Precursors  

NASA Astrophysics Data System (ADS)

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 mismatch of coordination between the activity dynamics of one type of biological indicators) were observed in one case before the November 12, 1987, event at a hypocenter distance of 8 km from the observation point (i.e., the animals were located within the source zone). (3) Changes observed before the earthquakes do not have any specific features and correspond quite well to the variations permanently observed without any relation to the earthquakes. (4) The activity of individual specimens has specific features. This hampers the implication of the biological monitoring. (5) The conclusions made here should not be considered absolute or extrapolated over all cases of observation of the behavior of animals, because the animals were kept under experimental (laboratory) conditions and could be screened from the influence of the stimuli of some modalities.

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



Improved Single-Source Precursors for Solar-Cell Absorbers  

NASA Technical Reports Server (NTRS)

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).

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



dl -threo-DOPS as a precursor of noradrenaline  

Microsoft Academic Search

dl-threo-Dihydroxyphenylserine (dl-threo-DOPS) is a non-physiological precursor of noradrenaline (NA). The formation of NA fromdl-threo-DOPS has been reported to occur in various mammalian tissue. Since NA deficiency is thought to be underlying mechanism in several neurological disorders, we studied the role of thedl-threo-DOPS as a precursor of NA. In rats treated withdl-threo-DOPS heart NA levels increased in a dose-dependent manner with

Avinoam Reches; Vernice Jackson-Lewis; Stanley Fahn



Precursors and e+\\/- pair loading from erupting fireballs  

Microsoft Academic Search

Recent observations suggest that long-duration gamma-ray bursts and their afterglows are produced by highly relativistic jets emitted in core-collapse explosions. As the jet makes its way out of the stellar mantle, a bow shock runs ahead and a strong thermal precursor is produced as the shock breaks out. Such erupting fireballs produce a very bright gamma-ray precursor as they interact

Enrico Ramirez-Ruiz; Andrew I. MacFadyen; Davide Lazzati



Stacked Optical Precursors from Amplitude and Phase Modulations  

SciTech Connect

We report the generation of stacked optical precursors from a laser beam whose amplitude or phase is modulated by sequenced on-off step waveforms. Making use of the constructive interference between the precursors produced from different steps, as well as the main field, we generate optical transient pulses having peak powers of eight times the input power with electromagnetically induced transparency in laser-cooled atoms.

Chen, J. F.; Feng, L.; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang [Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Jeong, Heejeong [Samsung Electronics Co., Ltd., Suwon, Gyeonggi (Korea, Republic of)



Synthesis of precursors of histamine peptides found in bee venom  

E-print Network

SYNTHESIS OF PRECURSORS OF HISTAMINE PEPTIDES FOUND IN BEE VENOM A Thesis by TIMOTHY JAMES JOHNSON Submitted to the graduate college of Texas AErM University in partial fulfillment of the requirement for the degree of MASTER OF SCIENCE... August 1975 Major SubJ'ect: Chemistry SYNTHESIS OF PRECURSORS OF HISTAMINE PEPTIDES FOUND IN BEE VENOM A Thesis by Timothy James Johnson Approved as to style and content by: Chairman of Committee) (Head of Department) (Me er) (M mber) (Memb r...

Johnson, Timothy James



Active unfolding of precursor proteins during mitochondrial protein import.  

PubMed Central

Precursor proteins made in the cytoplasm must be in an unfolded conformation during import into mitochondria. Some precursor proteins have tightly folded domains but are imported faster than they unfold spontaneously, implying that mitochondria can unfold proteins. We measured the import rates of artificial precursors containing presequences of varying length fused to either mouse dihydrofolate reductase or bacterial barnase, and found that unfolding of a precursor at the mitochondrial surface is dramatically accelerated when its presequence is long enough to span both membranes and to interact with mhsp70 in the mitochondrial matrix. If the presequence is too short, import is slow but can be strongly accelerated by urea-induced unfolding, suggesting that import of these 'short' precursors is limited by spontaneous unfolding at the mitochondrial surface. With precursors that have sufficiently long presequences, unfolding by the inner membrane import machinery can be orders of magnitude faster than spontaneous unfolding, suggesting that mhsp70 can act as an ATP-driven force-generating motor during protein import. PMID:9362487

Matouschek, A; Azem, A; Ratliff, K; Glick, B S; Schmid, K; Schatz, G



Elements of the tsunami precursors' detection physics  

NASA Astrophysics Data System (ADS)

In accordance with the main physical principles and geophysical data, we formulated a nonlinear mathematical model of seismo-hydro-electromagnetic (EM) geophysical field interaction and calculated generation and propagation of elastic, EM, temperature and hydrodynamic seismically generated disturbances (i.e. signals) in the basin of a marginal sea. We show transferring of seismic and electromagnetic (EM) energy from the upper mantle beneath the sea into its depths and EM emission from the sea surface into the atmosphere. Basing on the calculated characteristics of the signals of different physical nature (computations correspond to measurements of other authors) we develop the project of a Lithosphere-Ocean-Atmosphere Monitoring System (LOAMS) including: a bottom complex, a moored ocean surface buoy complex, an observational balloon complex, and satellite complex. The underwater stations of the bottom complex of the LOAMS will record the earlier signals of seismic activation beneath a seafloor (the ULF EM signals outrun seismic ones, according to the above calculations) and localize the seafloor epicenter of an expected seaquake. These stations will be equipped, in particular, with: magnetometers, the lines for the electric field measurements, and magneto-telluric blocks to discover dynamics of physical parameters beneath a sea floor as signs of a seaquake and/or tsunami preparation process. The buoy and balloon complexes of the LOAMS will record the meteorological and oceanographic parameters' variations including changes of reflection from a sea surface (tsunami ‘shadows’) caused by a tsunami wave propagation. Cables of the balloon and moored buoy will be used as receiving antennas and for multidisciplinary measurements including gradients of the fields (we show the cases are possible when the first seismic EM signal will be registered by an antenna above a sea). Also, the project includes radio-tomography with satellite instrumentation and sounding of the 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.

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


Urinary ?-hydroxybutyrate concentrations in 1126 female subjects.  


?-Hydroxybutyrate (GHB) and its metabolic precursor ?-butyrolactone (GBL) are often implicated in cases of drug-facilitated sexual assault (DFSA), although definitive confirmation of GHB/GBL ingestion is complicated by GHB's endogenous nature and rapid elimination following ingestion. Multiple studies have attempted to establish a discriminant limit (generally 10 mg/L) above which urinary GHB concentrations can be considered consistent with GHB/GBL consumption. To supplement the currently available data, a rapid gas chromatography-mass spectrometry method was developed and validated for the analysis of GHB (following acidic conversion to GBL) and used to analyze urine samples collected from 1126 women (mean = 0.84 mg/L, median = 0.68 mg/L, range = 0.00-5.5 mg/L). GHB concentrations were shown to be independent of urinary pH (within the range 4.6-9.3), age (within the range 18-35 years), body mass index (within the range 13.8-36.3), and race. Adjusting GHB concentrations with respect to urinary specific gravity had little effect on the mean value (0.91 mg/L) and range (0.0-7.76 mg/L), although a statistically significant trend of increasing GHB concentration with specific gravity could be observed. Our results can be taken to offer further support for the 10 mg/L discriminant limit for GHB administration in antemortem urine samples. PMID:21073808

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



Alkoxide-based precursors for direct electrospinning of alumina fibers  

NASA Astrophysics Data System (ADS)

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.

Maneeratana, Vasana


Hydrokinetic simulations of nanoscopic precursor films in rough channels  

NASA Astrophysics Data System (ADS)

We report on simulations of capillary filling of highly wetting fluids in nanochannels with and without obstacles. We use atomistic (molecular dynamics) and hydrokinetic (lattice Boltzmann; LB) approaches which indicate clear evidence of the formation of thin precursor films, moving ahead of the main capillary front. The dynamics of the precursor films is found to obey a square-root law like that obeyed by the main capillary front, z^2(t) \\propto t , although with a larger prefactor, which we find to take the same value for the different geometries (2D-3D) under inspection. The two methods show a quantitative agreement which indicates that the formation and propagation of thin precursors can be handled at a mesoscopic/hydrokinetic level. This can be considered as a validation of the LB method and opens the possibility of using hydrokinetic methods to explore space-time scales and complex geometries of direct experimental relevance. Then, the LB approach is used to study the fluid behaviour in a nanochannel when the precursor film encounters a square obstacle. A complete parametric analysis is performed which suggests that thin-film precursors may have an important influence on the efficiency of nanochannel-coating strategies.

Chibbaro, S.; Biferale, L.; Binder, K.; Dimitrov, D.; Diotallevi, F.; Milchev, A.; Succi, S.



Unconsumed precursors and couplers after formation of oxidative hair dyes.  


Contact allergy to hair dye ingredients, especially precursors and couplers, is a well-known entity among consumers having hair colouring done at home or at a hairdresser. The aim of the present investigation was to estimate consumer exposure to some selected precursors (p-phenylenediamine, toluene-2,5-diamine) and couplers (3-aminophenol, 4-aminophenol, resorcinol) of oxidative hair dyes during and after hair dyeing. Concentrations of unconsumed precursors and couplers in 8 hair dye formulations for non-professional use were investigated, under the conditions reflecting hair dyeing. Oxidative hair dye formation in the absence of hair was investigated using 6 products, and 2 products were used for experimental hair dyeing. In both presence and absence of hair, significant amounts of unconsumed precursors and couplers remained in the hair dye formulations after final colour development. Thus, up to 1.1% p-phenylenediamine (PPD), 0.04% toluene-2,5-diamine, 0.02% 3-aminophenol and 0.02% resorcinol were found in the hair dye formulation after the required colour was developed. The consumers are thus exposed to precursors and couplers of oxidative hair dyes, both during and after hair dyeing, when the hair is washed. Furthermore, the consumers are also expected to be exposed to intermediates of oxidative hair dyes. The allergenic potential of oxidative hair dyes as well as the intermediates of these remains unknown. PMID:16930234

Rastogi, Suresh Chandra; Søsted, Heidi; Johansen, Jeanne Duus; Menné, Torkil; Bossi, Rossana



Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply.  


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

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



Precursors and electron-positron pair loading from erupting fireballs  

E-print Network

Recent observations suggest that long-duration gamma-ray bursts and their afterglows are produced by highly relativistic jets emitted in core-collapse explosions. As the jet makes its way out of the stellar mantle, a bow shock runs ahead and a strong thermal precursor is produced as the shock breaks out. Such erupting fireballs produce a very bright gamma-ray precursor as they interact with the thermal break-out emission. The prompt gamma-ray emission propagates ahead of the fireball before it becomes optically thin, leading to electron-positron pair loading and radiative acceleration of the external medium. The detection of such precursors would offer the possibility of diagnosing not only the radius of the stellar progenitor and the initial Lorentz factor of the collimated fireball, but also the density of the external environment.

Enrico Ramirez-Ruiz; Andrew I. MacFadyen; Davide Lazzati



Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors.  


Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest cells coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b) together with markers of Schwann cell precursors. Some give rise to Schwann cells after down-regulation of PHOX2b. Others form parasympathetic ganglia after being guided to the site of ganglion formation by the nerves that carry preganglionic fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development. PMID:24925912

Espinosa-Medina, I; Outin, E; Picard, C A; Chettouh, Z; Dymecki, S; Consalez, G G; Coppola, E; Brunet, J-F



Development on polymeric precursor routes to produce superconducting nanoparticles  

NASA Astrophysics Data System (ADS)

The well-known polymeric precursor route is a simple and low-cost sol-gel method based on the preparation of an aqueous precursor solution of metals followed by the addition of a water-soluble polymer. This method consists of a polyesterification process between a metal chelate complex by using a hydroxycarboxylic acid and a polyhydroxy alcohol. In this work, citric acid (CA), tartaric acid (TA) and ethylenediaminetetraacetic acid (EDTA) are used as the hydroxycarboxylic acid and ethylene glycol (EG) is used as the polyhydroxy alcohol. The effects of the precursor pH solution, time and temperature of polymerization step as well as the combination of different chelating agents in order to obtain nanoscopic YBa 2Cu 3O y samples were traced.

Lisboa-Filho, P. N.; Motta, M.; Saeki, M. J.



Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply  

PubMed Central

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

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



Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply  

NASA Astrophysics Data System (ADS)

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.

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



Synthetic precursor to vertical TiO2 nanowires  

NASA Astrophysics Data System (ADS)

An easy protocol for improvement in formation of the photoanode in a dye sensitized solar cell is addressed. Specifically, a novel synthesis for the formation of a TiO2 precursor: titanium butanediolate, is detailed. This precursor is found to have higher thermal and temporal stability than commercially available TiO2 precursors and it has successfully been employed in the one-pot synthesis of rutile nanowires grown directly on a conducting substrate: fluorine doped tin oxide (FTO). This synthesis has been further extended to directly form a mixed phase TiO2 film consisting of rutile nanowires along with anatase spherical particles on FTO and this assembly has been used as the photoanode in a dye-sensitized solar cell. The synergistic effect of the two phases has provided a net DSSC efficiency of 4.61% with FF = 61%.

Mishra, B.; Ghildiyal, P.; Agarkar, S.; Khushalani, D.



The behaviors of optimal precursors during wintertime Eurasian blocking onset  

NASA Astrophysics Data System (ADS)

In this paper the optimal precursors for wintertime Eurasian blocking onset are acquired by solving a nonlinear optimization problem whose objective function is constructed based on a blocking index with a triangular T21, three-level, quasi-geostrophic global spectral model. The winter climatological state is chosen as the reference basic state. Numerical results show that the optimal precursors are characterized by a baroclinic pattern with a westward tilt with height, which are mainly located upstream of the blocking region. For an optimization time of 5 days, these perturbations are mainly localized over the Northeast Atlantic Ocean and continental Europe. With the extension of the optimization time to 8 days, these perturbations are distributed more upstream and extensively in the zonal direction. Wave spectrum analysis reveals that the optimal precursors are composed of not only synoptic-scale (wave numbers 5-18) waves, but planetary-scale (wave numbers 0-4) waves as well. The synoptic-scale optimal precursors are mainly located in the mid-latitude area, while the planetary-scale optimal precursors focus primarily on the high-latitude region. The formation of a strong planetary-scale positive blocking anomaly is accompanied by the reinforcement of synoptic-scale perturbations and further fragmentation into two branches, in which the northern branch is generally stronger than the southern one. The eddy forcing arising from the self-interaction of synoptic-scale disturbances is shown to be crucial in triggering the dipole blocking anomaly, and the planetary-scale optimal precursor provides the initial favorable background conditions for blocking onset.

Jiang, Zhina; Wang, Donghai



Precursor Exploration Missions in Kelly Lake, British Columbia- MARSLIFE project  

NASA Astrophysics Data System (ADS)

Precursor missions are an integral step in coordinated exploration between unmanned and manned systems both for terrestrial and astrobiology applications. Testing and developing the protocols for efficient, safe, and meaningful precursor missions is a key step in readiness for space exploration and is integral to the new MARSLIFE analogue research project. Here we present first-year field results from the use of an autonomous underwater vehicle (AUV) to conduct high-resolution (<1 m/pixel) geoacoustic mapping (bathymetry and backscatter) of the MARSLIFE field site. Rapid operations and quick-turn-around data-processing (within 1 - 2 days) allowed us to provide our precursor mission data in the form of digital maps to the MARSLIFE operating team for site assessment and mission planning. Precursor mapping helped identify target areas for specific operations, including ROV and Deepworker missions during the field campaign. Mission critical results from the AUV survey included morphology (micro-bathymetry), target localization, and suitability of terrain types based on slope and rugosity for different mission activities (e.g. SCUBA slope transects and water samples). The rapid acquisition and data processing turn around allowed us to provide mission critical measurements such as depth, slope, composition, and roughness to the entire exploration team. In total during the July 2010 field campaign, over 3 days of intensive AUV and ROV missions were run in Kelly Lake resulting in nearly 50 km of trackline data (side-scan sonar, swath bathymetry, color video, and water quality measurements) of the lake at sub-meter resolution in side-scan sonar and interferometric swath bathymetry resulting in precursor derived geoacoustic maps that will facilitate the safe and expedient follow-on exploration from subsequent manned missions in the next field season. During the course of the precursor AUV missions distinct patches of shallow and deep microbialites were mapped at a spatial resolution of 0.5 m/pixel providing the first detailed bathymetric charts for this alpine lake.

Trembanis, A. C.; Gutsche, J.; Nebel, S. H.



Direct observation of optical precursors in a cold potassium gas  

NASA Astrophysics Data System (ADS)

This thesis considers how an electromagnetic field propagates through a dispersive linear dielectric in the case when the field is turned on suddenly. It has been predicted nearly 100 years ago that the point in the waveform where the field first turns on (the front) propagates precisely at the speed of light in vacuum. Furthermore, it is predicted that distinct wave-packets develop after the front, but before the arrival of the main part of the field (the main signal). These wave-packets are known as optical precursors. It was believed that precursors are an ultra-fast phenomena, persisting only for a few optical cycles, and that they have an exceedingly small amplitude. I describe a method to increase the duration of optical precursors into the nanosecond range using a dielectric with a narrow resonance. I also show how to increase the precursor amplitude by tuning the carrier frequency of the field near the resonance frequency of the oscillators making up the dielectric medium. The field emerging from the dielectric consists of a several-nanosecond-long spike occurring immediately after the front with near 100% transmission, which subsequently decays to a constant value expected from Beer's Law of absorption. I demonstrate, using a modern asymptotic theory, that the spike consists of both the Sommerfeld and Brillouin precursors. Thus, my measurement is the first direct observation of optical precursors. The precursor research might be useful for imaging applications requiring penetrating optical radiation, such as in biological systems, or in optical communication systems. While the asymptotic theory explains qualitatively my observations, I find that there are large quantitative disagreements. I hypothesize that these errors are due to the fact that I use a weakly-dispersive narrow-resonance medium for which this theory has never been tested. I suggest empirical fixes to the theory by comparison to my data. I also compare the asymptotic theory and data to a second theory that is known to describe well my experimental conditions, but was believed by some researchers not to predict optical precursors. I demonstrate that this belief is incorrect.

Jeong, Heejeong


Process for producing ceramic nitrides and carbonitrides and their precursors  


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.

Brown, Gilbert M. (Knoxville, TN); Maya, Leon (Oak Ridge, TN)



Proliferation and Programmed Cell Death of Neuronal Precursors in the  

E-print Network

Proliferation and Programmed Cell Death of Neuronal Precursors in the Mushroom Bodies¨t Berlin, 14195 Berlin, Germany ABSTRACT We have studied proliferation and programmed cell death in the brain of the honeybee during metamorphosis. DNA fragmentation detection using the TUNEL method combined

Menzel, Randolf - Institut für Biologie


Observations of Precursor Ionization in Electromagnetic T Tubes  

Microsoft Academic Search

Experimental measurements of electron number densities in the precursor region of Mach 5 shocks in xenon have been conducted. The ionization is attributed to 1200-3000-Å radiation and is due primarily to the presence of impurities in the vacuum system.

Thomas G. McRae; B. M. Leadon



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

NASA Astrophysics Data System (ADS)

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.

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



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

NASA Technical Reports Server (NTRS)

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.

Groen, Frank; Lutomski, Michael



Measurement of excitation energy of neutron-rich precursor fragments  

NASA Astrophysics Data System (ADS)

Projectile fragmentation forms the basis for beam production at radioactive beam facilities such as the National Superconducting Cyclotron Laboratory (NSCL), yet uncertainties remain about the specifics of the production mechanism. For example, very little is known about the excitation energy of the precursors of the observed final fragments. In the present work, isotopes of sodium, neon, and fluorine produced in the fragmentation of a 32 Mg beam at 86 MeV/nucleon in a beryllium target, ranging in mass loss from DeltaA = 3--12, were observed and the coincident neutrons were detected using the Modular Neutron Array (MoNA). Neutron hit multiplicity in MoNA was compared to output from the statistical evaporation model PACE which was passed through a GEANT4 simulation to account for detector response with a X2v analysis. The neutron hit multiplicity distributions were used to determine the mass loss and excitation energy of the precursor fragments created in the fast step of the reaction. The mass loss and excitation energy were compared to abrasion/ablation models and an internuclear cascade model, ISABEL. For sodium and neon observed fragments, a single precursor mass was found, with a wide range of high excitation energies, up to 60 MeV. Observed fluorine isotopes were also found to have high excitation energies, ranging from 40--80 MeV, but with some variation in precursor mass.

Mosby, Michelle Anthea


Apoptotic Osteocytes Regulate Osteoclast Precursor Recruitment and Differentiation In Vitro  

E-print Network

Apoptotic Osteocytes Regulate Osteoclast Precursor Recruitment and Differentiation In Vitro Saja A, Toronto, ON, Canada ABSTRACT Fatigue loading causes a spatial distribution of osteocyte apoptosis co-localized with bone resorption spaces peaking around microdamage sites. Since osteocytes have been shown to regulate

You, Lidan



EPA Science Inventory

The use of ozone combined with ultraviolet radiation has been studied at the pilot-scale for removing trihalomethane (THM) precursors from potable water. The effects of variations in ozone dose rate, UV intensity and other parameters were first studied using a synthetic feedwater...


Synthesis and use of a trifluoromethylated azomethine ylide precursor.  


The presence of fluorous substituents can impart a dramatic effect on the efficacy of molecules used for a range of applications in society. Here, we describe the preparation and use of a new trifluoromethylated azomethine ylide precursor, which leads to a series of fluorinated pyrrolidine, 3-pyrroline, and pyrrole building blocks. PMID:23176732

Tran, Gaël; Meier, Robin; Harris, Lawrence; Browne, Duncan L; Ley, Steven V



Geoelectric potential changes: Possible precursors to earthquakes in Japan  

Microsoft Academic Search

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

S. Uyeda; T. Nagao; Y. Orihara; T. Yamaguchi; I. Takahashi



Improved removals of trihalomethane precursors by small water supply systems  

Microsoft Academic Search

Selected slow sand filter modifications that could enhance the principal removal mechanisms of biodegradation and adsorption and would not compromise the simplicity of the treatment process were explored in research conducted at the University of New Hampshire. The modifications were evaluated for their potential to improve removal of trihalomethanes (THM) precursor material and particulate matter over conventionally operated slow sand

M. R. Collins; T. T. Eighmy; J. M. Fenstermacher; S. K. Spanos; C. M. Spencer



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

ERIC Educational Resources Information Center

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…

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



Process for producing ceramic nitrides anc carbonitrides and their precursors  


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.

Brown, G.M.; Maya, L.




EPA Science Inventory

The report gives results of an analysis of national and regional acid deposition precursor emission trends, involving SOx, NOx, and VOCs. While the focus is on emissions during 1980-1985, comparisons are made (for perspective) with emission trends for 1940-1980. Study methods int...


Environment Conscious, Biomorphic Ceramics from Pine and Jelutong Wood Precursors  

NASA Technical Reports Server (NTRS)

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.

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



Precursor Lesions of Pancreatic Cancer: Molecular Pathology and Clinical Implications  

Microsoft Academic Search

Background: Pancreatic cancer is a lethal disease, with near uniform 5-year mortality rates. The key to improving survival of pancreatic cancer rests upon early detection of this neoplasm at a resectable, and hence potentially curable, stage. Methods: We review the current state of the literature vis-à-vis the three common precursor lesions of pancreatic adenocarcinoma: pancreatic intraepithelial neoplasia, intraductal papillary mucinous

Mansher Singh; Anirban Maitra



INTRODUCTION An organ primordium consists of precursor cells that generate  

E-print Network

: it is composed of two somatic gonadal precursor cells (SGPs) and two primordial germ cells (PGCs). The SGPs generate all somatic tissues of the gonad proper (i.e. ovary or testis), as well as genital ducts (e embryogenesis (Fig. 1A,B) (Sulston et al., 1983). Within the mature primordium, the SGPs (Z1 and Z4) reside

Kimble, Judith


Introduction Metal acetates are used as metal precursors in many  

E-print Network

facilitated exploring broader applications of metal and metal oxide nanoparticles by utilizing the synthesis properties of the solid phase metal acetate precursors and the product metal/metal oxide nanocomposite in these combustion and other synthesis systems which rely on thermal decomposition and oxidation of metal acetates [6

Wooldridge, Margaret S.


Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function  

PubMed Central

Increased osteoclastic bone resorption leads to periarticular erosions and systemic osteoporosis in RA patients. Although a great deal is known about how osteoclasts differentiate from precursors and resorb bone, the identity of an osteoclast precursor (OCP) population in vivo and its regulatory role in RA remains elusive. Here, we report the identification of a CD11b–/loLy6Chi BM population with OCP activity in vitro and in vivo. These cells, which can be distinguished from previously characterized precursors in the myeloid lineage, display features of both M1 and M2 monocytes and expand in inflammatory arthritis models. Surprisingly, in one mouse model of RA (adoptive transfer of SKG arthritis), cotransfer of OCP with SKG CD4+ T cells diminished inflammatory arthritis. Similar to monocytic myeloid-derived suppressor cells (M-MDSCs), OCPs suppressed CD4+ and CD8+ T cell proliferation in vitro through the production of NO. This study identifies a BM myeloid precursor population with osteoclastic and T cell–suppressive activity that is expanded in inflammatory arthritis. Therapeutic strategies that prevent the development of OCPs into mature bone-resorbing cells could simultaneously prevent bone resorption and generate an antiinflammatory milieu in the RA joint. PMID:23114597

Charles, Julia F.; Hsu, Lih-Yun; Niemi, Erene C.; Weiss, Arthur; Aliprantis, Antonios O.; Nakamura, Mary C.




EPA Science Inventory

A project was conducted to determine and improve the ability of the magnesium carbonate process to remove trihalomethane (THM) precursors in treated drinking water. The project was conducted at a drinking water treatment plant in Melbourne, FL, which had been developed and instal...



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...


Supercritical antisolvent precipitation of nanoparticles of a zinc oxide precursor  

Microsoft Academic Search

Supercritical antisolvent (SAS) precipitation has been applied to the production of zinc acetate with the aim of evaluating the applicability of this new process to the production of controlled size nanoparticles of catalyst precursors. SAS process is based on the large volumetric expansion of the liquid solvent induced by the fast diffusion of the antisolvent inside the liquid phase. The

E Reverchon; G Della Porta; D Sannino; P Ciambelli



Precursors to ?-ray bursts in the asteroid impact scenario  

Microsoft Academic Search

The extremely large energy densities in the fireball of a ?-ray burst lead to copious pair production and annihilation independent of the burst mechanism. The spectrum and time behavior of the burst itself thus may not be useful in distinguishing between endogenic and exogenic mechanisms. Asteroid impacts onto neutron stars can give rise to burst precursors as material from the

Dave Van Buren



Study on the precursor for atomic oxygen resistant coating  

NASA Astrophysics Data System (ADS)

A coating of atomic oxygen resistant was obtained through sol-gel method, and the precursors for the coating were synthesized and analyzed. The precursor liquid was prepared using methacryloxypropyltrimethoxysilane (MAPTMS) and tetraethylorthosilicate (TEOS). In order to get a stable and clear liquid, different procedures of synthesis, different stirring time, different synthesis temperature, water amount, and other additives were considered. IR spectra and experiments of DSC of different precursor liquids were compared, and the effect of Si-O and O-H groups was discussed. The results demonstrated that the amount of TEOS additions has greater effects on the bond strength. It is agreed with greater Si-O ratio in a single molecule TEOS than in silane. SEM experiment gives that they also possess the good performance on the atomic oxygen (AO) exposed resistant. The SEM pictures showed almost no change between the coatings with and without AO exposure. Necessary heat treat time for the precursor depends on the silane to silica sol ratio, and the heat treatment temperature, heat-treatment time.

Luo, Zhongkuan; Liu, Jianhong; Hong, Weiliang; Tian, Deyu; Cai, Honghua; Xu, Hong; Tang, Shaojin; Zhu, Ruixiang



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...


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,...


Laser Microdissection of Sensory Organ Precursor Cells of Drosophila Microchaetes  

PubMed Central

Background In Drosophila, each external sensory organ originates from the division of a unique precursor cell (the sensory organ precursor cell or SOP). Each SOP is specified from a cluster of equivalent cells, called a proneural cluster, all of them competent to become SOP. Although, it is well known how SOP cells are selected from proneural clusters, little is known about the downstream genes that are regulated during SOP fate specification. Methodology/Principal Findings In order to better understand the mechanism involved in the specification of these precursor cells, we combined laser microdissection, toisolate SOP cells, with transcriptome analysis, to study their RNA profile. Using this procedure, we found that genes that exhibit a 2-fold or greater expression in SOPs versus epithelial cells were mainly associated with Gene Ontology (GO) terms related with cell fate determination and sensory organ specification. Furthermore, we found that several genes such as pebbled/hindsight, scabrous, miranda, senseless, or cut, known to be expressed in SOP cells by independent procedures, are particularly detected in laser microdissected SOP cells rather than in epithelial cells. Conclusions/Significance These results confirm the feasibility and the specificity of our laser microdissection based procedure. We anticipate that this analysis will give new insight into the selection and specification of neural precursor cells. PMID:20174573

Buffin, Eulalie; Gho, Michel



Precursors to Numeracy in Kindergartners with Specific Language Impairment  

ERIC Educational Resources Information Center

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…

Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo



Compromised Hemodynamic Response in Amyloid Precursor Protein Transgenic Mice  

Microsoft Academic Search

APP23 transgenic mice overexpressing amyloid precursor pro- tein (APP751 ) reproduce neuropathological changes associated with Alzheimer's disease such as high levels of amyloid plaques, cerebral amyloid angiopathy, and associated vascular patholo- gies. Functional magnetic resonance imaging (fMRI) was applied to characterize brain functionality in these mice through global pharmacological stimulation. The cerebral hemodynamic re- sponse to infusion of the GABAA

Thomas Mueggler; Christine Sturchler-Pierrat; Diana Baumann; Martin Rausch; Matthias Staufenbiel; Markus Rudin



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...


Introduction In many vertebrate cell lineages, precursor cells divide a  

E-print Network

been studying the stopping mechanisms in the oligodendrocyte cell lineage in the rodent optic nerve. Oligodendrocyte precursor cells (OPCs) migrate from the brain into the developing rat optic nerve before birth differentiate into oligodendrocytes (Temple and Raff, 1986), which then myelinate the axons in the nerve

Richardson, William D.


The oligodendrocyte precursor cell in health and disease  

Microsoft Academic Search

Adult oligodendrocyte precursor cells (OPCs) make up around 5–8% of the glial cell population in the CNS. Their function in the undamaged CNS is largely unknown, but their processes are in contact with nodes of Ranvier and synapses, suggesting a regulatory role at these structures. The cells divide slowly, and constitute ?70% of cells labelled following a pulse injection of

Joel M Levine; Richard Reynolds; James W Fawcett



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


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. PMID:17725882

Quest, Dale W; Horsley, Joanne



Making Single-Source Precursors of Ternary Semiconductors  

NASA Technical Reports Server (NTRS)

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 semiconductor CuInS2.

Hepp, Aloysius; Banger, Kulbindre K.



Whole-cell fungal transformation of precursors into dyes  

PubMed Central

Background Chemical methods of producing dyes involve extreme temperatures and unsafe toxic compounds. Application of oxidizing enzymes obtained from fungal species, for example laccase, is an alternative to chemical synthesis of dyes. Laccase can be replaced by fungal biomass acting as a whole-cell biocatalyst with properties comparable to the isolated form of the enzyme. The application of the whole-cell system simplifies the transformation process and reduces the time required for its completion. In the present work, four fungal strains with a well-known ability to produce laccase were tested for oxidation of 17 phenolic and non-phenolic precursors into stable and non-toxic dyes. Results An agar-plate screening test of the organic precursors was carried out using four fungal strains: Trametes versicolor, Fomes fomentarius, Abortiporus biennis, and Cerrena unicolor. Out of 17 precursors, nine were transformed into coloured substances in the presence of actively growing fungal mycelium. The immobilized fungal biomass catalyzed the transformation of 1 mM benzene and naphthalene derivatives in liquid cultures yielding stable and non-toxic products with good dyeing properties. The type of fungal strain had a large influence on the absorbance of the coloured products obtained after 48-hour transformation of the selected precursors, and the most effective was Fomes fomentarius (FF25). Whole-cell transformation of AHBS (3-amino-4-hydroxybenzenesulfonic acid) into a phenoxazinone dye was carried out in four different systems: in aqueous media comprising low amounts of carbon and nitrogen source, in buffer, and in distilled water. Conclusions This study demonstrated the ability of four fungal strains belonging to the ecological type of white rot fungi to transform precursors into dyes. This paper highlights the potential of fungal biomass for replacing isolated enzymes as a cheaper industrial-grade biocatalyst for the synthesis of dyes and other commercially important products. The use of immobilized fungal biomass limits free migration of cells and facilitates their reuse in a continuous system for precursor transformation. PMID:20598166



Hormonal effects on proliferation of adipocyte precursor cells isolated from chicken enbryos  

E-print Network

Influence of glucagon (GLU), insulin (IN), growth hormone (GH) , and triiodothyronine (T3) on proliferation of chicken adipocyte precursor cells was examined. Adipocyte precursor cells were isolated from subcutaneous and f emoral adipose depots from...

Wu, Ying-Jen



Precursors in the preparation of transition metal nitrides and transition metal carbonitrides and their reaction intermediates  


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.

Maya, Leon (Oak Ridge, TN)



Directed differentiation of telencephalic precursors from embryonic stem cells.  


We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells ( approximately 90%). In the presence of Dkk1, with or without LeftyA, SFEB induces efficient generation ( approximately 35%) of cells expressing telencephalic marker Bf1. Wnt3a treatment during the late culture period increases the pallial telencephalic population (Pax6(+) cells yield up to 75% of Bf1(+) cells), whereas Shh promotes basal telencephalic differentiation (into Nkx2.1(+) and/or Islet1/2(+) cells) at the cost of pallial telencephalic differentiation. Thus, in the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals. PMID:15696161

Watanabe, Kiichi; Kamiya, Daisuke; Nishiyama, Ayaka; Katayama, Tomoko; Nozaki, Satoshi; Kawasaki, Hiroshi; Watanabe, Yasuyoshi; Mizuseki, Kenji; Sasai, Yoshiki



Detection of hydrothermal precursors to large northern california earthquakes.  


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. PMID:17738277

Silver, P G; Valette-Silver, N J



Characterization studies of purified HgI 2 precursors  

NASA Astrophysics Data System (ADS)

The ability of HgI 2 powders, used as precursors in mercuric iodide crystal growth, to produce high-quality detectors may be predicted by non-destructive methods like photoluminescence. In fact, it is possible to correlate the presence and the intensity ratio of specific bands in the photoluminescence spectrum of a HgI 2 crystal to its impurity content and stoichiometry. These quantities determine the detector grade that may be achieved using that starting material. Nine different HgI 2 precursors, obtained by different purification methods, have been characterized. The lowest impurity content is achieved via poly-ethylene treatment, which gives also a powder of relatively good stoichiometric quality.

Schieber, M.; Zuck, A.; Sanguinetti, S.; Montalti, M.; Braiman, M.; Melekhov, L.; Nissenbaum, J.; Grilli, E.; Guzzi, M.; Turchetta, R.; Dulinski, W.; Husson, D.; Riester, J. L.



Directed differentiation of telencephalic precursors from embryonic stem cells  

Microsoft Academic Search

We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells (?90%). In the presence of Dkk1, with or without LeftyA, SFEB induces efficient generation (?35%)

Kiichi Watanabe; Daisuke Kamiya; Ayaka Nishiyama; Tomoko Katayama; Satoshi Nozaki; Hiroshi Kawasaki; Yasuyoshi Watanabe; Kenji Mizuseki; Yoshiki Sasai



Approach to accurately measuring the speed of optical precursors  

SciTech Connect

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.

Li Chuanfeng; Zhou Zongquan; Guo Guangcan [Key Laboratory of Quantum Information, University of Science and Technology of China, CAS, Hefei 230026 (China); Jeong, Heejeong [Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, 03755 (United States)



Structures of new nitrides prepared using solid oxide precursors  

SciTech Connect

Several novel transition metal nitrides and oxynitrides were synthesized via ammonolysis of solid state oxide precursors at temperatures ranging from 700 C--900 C and reaction times ranging from 12 hours to 4 days. The products were characterized by powder X-ray diffraction and their structures were determined by powder X-ray Rietveld refinement. The relationships between the structures of these nitrides and oxynitrides, and their similarity to the structures of the transition metal dichalcogenides, is discussed.

Houmes, J.D.; Bem, D.S.; Loye, H.C. zur [Massachusetts Inst. of Tech., Cambridge, MA (United States). Dept. of Chemistry



COS in the stratosphere. [sulfuric acid aerosol precursor  

NASA Technical Reports Server (NTRS)

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.

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



Liquid Metal Carboxylates as Precursors for Aluminum-Containing Ceramics  

Microsoft Academic Search

Liquids salts of aluminum, magnesium, and yttrium were prepared via the reaction of 2-[2-(2-methoxy)ethoxy]ethoxyacetic acid (MEEA) with aluminum basic acetate, magnesium hydroxide, or yttrium carbonate, respectively. These salts may be used to prepare liquid precursors for binary aluminum-containing ceramics by dissolution of metal nitrates in one of the liquid metal carboxylates. In this manner, preceramic liquids were synthesized that yielded

Allen W. Apblett; Larry E. Reinhardt; Edwin H. Walker Jr



Wogonin induces differentiation and neurite outgrowth of neural precursor cells  

Microsoft Academic Search

Wogonin is a flavonoid isolated from Scutellaria baicalensis root, and has multiple pharmacological effects, including anti-inflammatory, anti-oxidant, and anti-cancer effects. It is also neuroprotective in the brain under many stress conditions, but wogonin does not elevate neuronal cell survival. Thus, the mechanisms controlling the neuroprotective effect of wogonin are not clear. Neural precursor cells (NPCs), present in the hippocampus and

Jung Su Lim; Minjoo Yoo; Hyun Jung Kwon; Hyosup Kim; Yunhee Kim Kwon



Processing of tumour necrosis factor-alpha precursor by metalloproteinases  

Microsoft Academic Search

TUMOUR necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory and immunomodulatory cytokine implicated in inflammatory conditions such as rheumatoid arthritis, Crohn's disease, multiple sclerosis and the cachexia associated with cancer or human immunodeficiency virus infection1. TNF-alpha is initially expressed as a 233-amino-acid membrane-anchored precursor which is proteolytically processed to yield the mature, 157-amino-acid cytokine2. The processing enzyme(s) which cleave TNF-alpha are

A. J. H. Gearing; P. Beckett; M. Christodoulou; M. Churchill; J. Clements; A. H. Davidson; A. H. Drummond; W. A. Galloway; R. Gilbert; J. L. Gordon; T. M. Leber; M. Mangan; K. Miller; P. Nayee; K. Owen; S. Patel; W. Thomas; G. Wells; L. M. Wood; K. Woolley



A photocrosslinkable melt processible acrylonitrile terpolymer as carbon fiber precursor  

Microsoft Academic Search

A novel photocrosslinkable and melt processible terpolymer precursor for carbon fiber has been successfully synthesized and characterized. The terpolymer was synthesized by an efficient emulsion polymerization route and has a typical composition of acrylonitrile\\/methyl acrylate\\/acryloyl benzophenone in the mole ratio, 85\\/14\\/1. It has been characterized by FTIR, NMR, intrinsic viscosity and GPC molecular weights. The composition of the monomer repeat

T. Mukundan; V. A. Bhanu; K. B. Wiles; H. Johnson; M. Bortner; D. G. Baird; A. K. Naskar; A. A. Ogale; D. D. Edie; J. E. McGrath



The molecular evolution of the allatostatin precursor in cockroaches  

Microsoft Academic Search

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 craniifer and Supella longipalpa. The sequences obtained are similar to those of Diploptera punctata and Periplaneta americana reported previously.

Xavier Bellés; Laurie A. Graham; William G. Bendenab; Qi Ding; John P. Edwards; Robert J. Weaver; Stephen S. Tobe



Beryllium10 in Australasian tektites: evidence for a sedimentary precursor  

Microsoft Academic Search

Each of seven Australasian tektites contains about 1 x 10⁸ atoms of beryllium-10 (half-life, 1.53 x 10⁶ 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

D. K. Pal; C. Tuniz; R. K. Moniot; T. H. Kruse; G. F. Herzog



Beryllium10 in Australasian tektites - Evidence for a sedimentary precursor  

Microsoft Academic Search

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.

D. K. Pal; R. K. Moniot; T. H. Kruse; G. F. Herzog; C. Tuniz



Beryllium10 in Australasian Tektites: Evidence for a Sedimentary Precursor  

Microsoft Academic Search

Each of seven Australasian tektites contains about 1 × 108 atoms of beryllium-10 (half-life, 1.53 × 106 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

John A. Westgate



Generation of amyloid ? protein from its precursor is sequence specific  

Microsoft Academic Search

Cerebral deposition of amyloid ? protein (A?) is an early and critical feature of Alzheimer's disease. Here we analyze the substrate requirements of proteases (“?-secretases”) that cleave the R-amyloid precursor protein (?APP) at the N-terminus of A? (Asp-597 of ?APP695)fis5) in intact human cells. The cleavage requires a membrane-bound substrate but tolerates shifts in the distance of the hydrolyzed bond

Martin Citron; David B Teplow; Dennis J Selkoe



The prevalence of hidradenitis suppurativa and its potential precursor lesions  

Microsoft Academic Search

Background: The morbidity of hidradenitis suppurativa can be considerable, but little is known about its epidemiology.Objective: Our purpose was to describe the 1-year and point prevalences of hidradenitis suppurativa and its potential precursor lesions.Methods: We obtained the histories and examined an unselected sample (599 persons) of the general population (1-year prevalence), and we performed physical examinations for a consecutive sample

Gregor B. E Jemec; Michael Heidenheim; Niels Henrik Nielsen



Preparation of ceramic coatings from pre-ceramic precursors  

Microsoft Academic Search

Scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) has indicated that adherent crack-free coatings of amorphous SiC and “Si3N4\\/Si2N2O” can be built up on planar alumina substrates by pyrolysis of layers of polycarbosilane (PCS) and poly(diphenyl)silazane (PDPS) precursors applied by spin- or dip-coating methods. In general, multilayers of black SiC can be prepared by pyrolysis of PCS layers

M. R. Mucalo; N. B. Milestone; I. C. Vickridge; M. V. Swain



Proteolytic Activation of the Interleukin-1? Precursor by Candida albicans  

PubMed Central

Chronic inflammation rather than invasion is characteristic of some forms of superficial candidiasis such as denture stomatitis. We hypothesized that Candida albicans may play a critical role in the pathogenesis of inflammatory lesions observed in chronic candidiasis by activating the proinflammatory cytokine interleukin-1? (IL-1?) from epithelial stores of the precursor. The aim of this study was therefore to demonstrate the proteolytic cleavage and activation of the inactive precursor of IL-1? (pro-IL-1?) by C. albicans. After incubation of either blastospores or hyphae with the inactive precursor, proteolytic cleavage was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western immunoblotting analysis, and the biological activity of the cleavage products was tested in a bioassay. We report here that late-stationary-growth-phase blastospores as well as hyphae of C. albicans, but not exponentially growing cells, can efficiently cleave pro-IL-1? to yield fragments of molecular masses compatible with mature biologically active IL-1? (17 to 19 kDa). Assays conducted in the presence of selected proteinase inhibitors suggest that the cleavage of pro-IL-1? involves the participation of one or more aspartyl proteinases. Cleavage products showed a dose-dependent IL-1?-like activity in a thymocyte proliferation bioassay, which was inhibited by anti-IL-1? neutralizing antibodies. The present data thus suggest a role for C. albicans proteinases in the activation and maintenance of the inflammatory response at epithelial surfaces. PMID:9453626

Beauséjour, Annie; Grenier, Daniel; Goulet, Jean-Paul; Deslauriers, Noëlla



Deposition of polyimide precursor by resonant infrared laser ablation  

NASA Astrophysics Data System (ADS)

We report the successful deposition of a polyimide precursor using resonant infrared laser ablation (RIR-LA). A solution of poly(amic acid) (PAA) dissolved in N-methyl-2-pyrrolidinone (NMP), the melt processable precursor to polyimide, was frozen in liquid nitrogen for use as an ablation target in a high-vacuum chamber. Fourier transform infrared spectroscopy was used to determine that the local chemical structure remained unaltered. Gel permeation chromatography demonstrated that the transferred PAA retained its molecular weight, showing that RIR-LA is able to transfer the polymer intact, with no detectable chain fragmentation. These results are in stark contrast to UV-processing which degrades the polymer. After deposition the PAA may be removed with a suitable solvent; however, once the material has undergone cyclodehydration it forms an impenetrable three-dimensional network associated with thermosetting polymers. The transfer of uncured PAA precursor supports the hypothesis that RIR-LA is intrinsically a low temperature process, because the PAA is transferred without reaching the curing temperature. The RIR-LA also effectively removes the solvent NMP from the PAA, during both the ablation and deposition phases; this is a necessary step in generating PI films.

Dygert, N. L.; Gies, A. P.; Schriver, K. E.; Haglund, R. F., Jr.



High divergence of the precursor peptides in combinatorial lanthipeptide biosynthesis.  


Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and post-translationally modified peptides (RiPPs). These compounds are widely distributed in taxonomically distant species, and their biosynthetic systems and biological activities are diverse. A unique example of lanthipeptide biosynthesis is the prochlorosin synthetase ProcM from the marine cyanobacterium Prochlorococcus MIT9313, which transforms up to 29 different precursor peptides (ProcAs) into a library of lanthipeptides called prochlorosins (Pcns) with highly diverse sequences and ring topologies. Here, we show that many ProcM-like enzymes from a variety of bacteria have the capacity to carry out post-translational modifications on highly diverse precursor peptides, providing new examples of natural combinatorial biosynthesis. We also demonstrate that the leader peptides come from different evolutionary origins, suggesting that the combinatorial biosynthesis is tied to the enzyme and not a specific type of leader peptide. For some precursor peptides encoded in the genomes, the leader peptides apparently have been truncated at the N-termini, and we show that these N-terminally truncated peptides are still substrates of the enzymes. Consistent with this hypothesis, we demonstrate that about two-thirds of the ProcA N-terminal sequence is not essential for ProcM activity. Our results also highlight the potential of exploring this class of natural products by genome mining and bioengineering. PMID:25244001

Zhang, Qi; Yang, Xiao; Wang, Huan; van der Donk, Wilfred A



Development of techniques for tagging precursor and essential chemicals  

SciTech Connect

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.

Swansiger, W.A.; Shepodd, T.J. [Sandia National Labs., Livermore, CA (United States); Phillips, M.L.F. [Sandia National Labs., Albuquerque, NM (United States)



Serrated and non-serrated precursor lesions of colorectal cancer.  


Although often viewed as a single disease, colorectal cancer more accurately represents a family of diseases with different precursor lesions. Conventional (tubular, tubulovillous and villous) adenomas are the most common neoplastic lesions occurring in the large intestine. They have adenomatous polyposis coli (APC) mutations and arise from dysplastic aberrant crypt foci, initially as polyclonal lesions. In sporadic tumours, neoplastic progression follows the traditional pathway (chromosomal instability pathway), resulting in CpG island methylator phenotype (CIMP)-negative, microsatellite-stable (MSS), BRAF and KRAS wild-type cancers. Germline mutations in the APC gene lead to familial adenomatous polyposis. Conventional adenomas are also the precursors of Lynch syndrome-associated microsatellite-instable (MSI-high) cancers. Sessile serrated adenoma/polyp (SSA/P) is the principal precursor lesion of the serrated pathway, in which BRAF mutation can lead to colorectal cancer with MSI-high CIMP-high or MSS CIMP-high phenotype. SSA/Ps have been associated with synchronous and metachronous invasive adenocarcinomas as well as so-called interval carcinomas. Serrated polyposis is rare but most likely underdiagnosed. Affected individuals bear an increased but unspecified risk for the development of colorectal cancer; close endoscopic surveillance is warranted. Traditional serrated adenomas (TSAs) are much less common than the other serrated lesions. Cancers originating from TSAs may show KRAS mutation with a CIMP-high MSS phenotype. PMID:25531494

Langner, Cord



LWIR hyperspectral imaging application and detection of chemical precursors  

NASA Astrophysics Data System (ADS)

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.

Lavoie, Hugo; Thériault, Jean-Marc; Bouffard, François; Puckrin, Eldon; Dubé, Denis



Thermogravimetric evaluation of the suitability of precursors for MOCVD  

NASA Astrophysics Data System (ADS)

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.

Kunte, G. V.; Shivashankar, S. A.; Umarji, A. M.



Laser synthesis of nanostructured ceramics from liquid precursors  

NASA Astrophysics Data System (ADS)

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.

Wilden, Johannes; Fischer, Georg



Identification of trail pheromone precursors from Subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae)  

Microsoft Academic Search

Whole-body extracts of the termite,Coptotermes formosanus Shiraki served for examining the presence of trail pheromone precursor(s). Three trail pheromone precursor candidates, identified as dodecatrienyl stearate, dodecatrienyl oleate, and dodecatrienyl linoleate, were isolated using various chromatographic methods in conjunction with bioassay and by capillary GC-MS analyses.

Masahiko Tokoro; Munezoh Takahashi; Ryohei Yamaoka



Precursor Selection and Process Conditions in the Preparation of Carbon Membrane for Gas Separation: A Review  

Microsoft Academic Search

Carbon membranes prepared by pyrolysis\\/carbonization of polymeric precursors have been studied in the last few years as a promising candidate for gas separation process. As the aim of this paper, a review on polymer precursor selection and effect of pyrolysis conditions on carbon membrane characteristics and performances were discussed in detail. A number of different polymer precursors have been surveyed

W. N. W. Salleh; A. F. Ismail; T. Matsuura; M. S. Abdullah



Preparation of Bi-Sr-Ca-Cu-O superconductors from oxide-glass precursors  


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.

Hinks, David G. (Lemont, IL); Capone, II, Donald W. (Northbridge, MA)



Progressing from Identification and Functional Analysis of Precursor Behavior to Treatment of Self-Injurious Behavior  

ERIC Educational Resources Information Center

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…

Dracobly, Joseph D.; Smith, Richard G.




Microsoft Academic Search

In this article, lyocell fiber is used as a precursor for carbon fiber. The mechanical properties of lyocell fiber and tenacity of carbon fiber from this precursor have been determined. Gray-relation analysis is used to investigate the relation between precursor's properties and the strength of the carbon fibers. The results suggested that the strength, force at breaking, and fineness of

Shunjin Peng; Huili Shao; Xuechao Hu



A phosphorylated, carboxy-terminal fragment of b-amyloid precursor protein localizes to the  

E-print Network

) is a neurodegenerative disorder of unknown etiology (1). A large body of evidence implicates b-amyloid precursor proteinA phosphorylated, carboxy-terminal fragment of b-amyloid precursor protein localizes; Revised December 15, 2003; Accepted January 2, 2004 b-Amyloid precursor protein (APP) is implicated

Muresan, Virgil


Management and treatment of gamma butyrolactone withdrawal syndrome: a case report and review.  


Gamma butyrolactone (GBL) is an increasingly popular drug of abuse that is readily available in most countries, and it is often purchased over the Internet. In addition to the acute hazards of intoxication and overdose, users who are dependent on GBL can also experience severe withdrawal reactions, including hallucinations, agitation, confusion, delusions, delirium, rhabdomyolysis, and seizures. Most of the existing literature suggests the use of a high-dose benzodiazepine as a first-line treatment for GBL withdrawal. However, several cases of resistance to benzodiazepines have been observed, which likely reflect some pharmacological differences between benzodiazepines and GBL. Specifically, the effects of benzodiazepines are primarily mediated by gamma-aminobutyric acid (GABA)-A receptors, while GBL and its analogues act mainly at GABA-B receptors, with possible additional effects via the ionotropic GABA-A receptors. In this regard, recent studies have found that GBL and its analogues possess a high affinity for a specific form of extrasynaptic GABA-A receptors that are strongly activated by barbiturates, such as phenobarbital, but that are insensitive to benzodiazepines. Taken together, these findings suggest that barbiturates could be evaluated as first-choice agents for the treatment of GBL/gamma hydroxybutyrate (GHB) withdrawal instead of benzodiazepines. In support of this view, we describe a clinical case of difficult to manage GBL withdrawal symptoms in a 42-year-old male. We also review the literature on treatment options for GBL/GHB withdrawal, including benzodiazepine-resistant withdrawal. PMID:25036586

Ghio, Lucio; Cervetti, Alice; Respino, Matteo; Belvederi Murri, Martino; Amore, Mario



[Acute gamma-butyrolactone poisoning with withdrawal syndrome].  


Gamma-butyrolactone (GBL) is a solvent that are part of many consumer products and in most countries can be legally purchased in the form of almost pure substance. After ingestion GBL is rapidly converted to gamma-hydroxybutyric acid (GHB). In recent years, GBL became a legal alternative to GHB, which is used widely since 1990s as a club drug and date rape drug. It is believed that abuse of GBL is not frequent in Europe, except for certain specific groups, mainly in urban centers in the west of the continent. We present a case of acute GBL poisoning with the withdrawal syndrome in 23-year-old man living in a rural area in eastern Poland. The patient was admitted to the Intensive Care Unit (ICU) because of coma of unknown origin. On admission erosions of the lips and mouth was seen. Ethyl alcohol was not present in blood sample, urine screening tests for drugs were negative. During his stay in the ICU patient required ventilatory support, was periodically agitated with muscular jerks and opisthotonos. The later medical history revealed that the patient from two years used GBL, which purchased as wheels cleaner. The tolerance developed, and the interruption of use of substance triggered symptoms of withdrawal. GBL abuse occurs in different social groups and is at risk for acute toxicity and the development of physical dependence. PMID:22010460

Chwaluk, Pawe?; Rejmak, Grazyna



WHO expert committee on drug dependence.  


This report presents the recommendations of a WHO Expert Committee responsible for reviewing information on psychoactive substances to assess the need for their international control. The report contains a summary of the Committee's evaluations of gamma-hydroxybutyric acid (GHB) and ketamine. GHB was recommended to be rescheduled from Schedule IV to Schedule II of the Convention on Psychotropic Substances. The report also discusses the nine substances that were pre-reviewed: dextromethorphan, tapentadol, N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP), 1-(4-methoxyphenyl)piperazine (MeOPP), 1-(3,4-methylenedioxybenzyl)piperazine (MDBP), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD). Of these, tapentadol, BZP, GBL and 1,4-BD were recommended for critical review. Issues identified for consideration at future Expert Committee meetings are also listed. Furthermore, the report discusses the use of terms, the use of pharmacovigilance data for the assessment of abuse and dependence potential, balancing medical availability and prevention of abuse of medicines manufactured from controlled substances, and improving the process for substance evaluation. PMID:24547667



Strain-induced dimensionality crossover of precursor modulations in Ni2MnGa  

NASA Astrophysics Data System (ADS)

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.

Nie, Zhihua; Wang, Yandong; Shang, Shunli; Zeng, Qiaoshi; Ren, Yang; Liu, Dongmei; Yang, Wenge; Wang, Yi; Liu, Zi-Kui



Possibility to study ionospheric earthquakes precursors using CubeSats  

NASA Astrophysics Data System (ADS)

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 values may be advisable to measure to study them: if for FWC - electrons density and temperature and electric field variations, if for AGW - neutral particles concentration and magnetic fields variations, and TEC variations and thermal anomalies at the Earth’s surface and in the atmosphere for both. Also it became clear that the monitoring has to be made minimum in two, better in three points, preferably with the possibility to control the distance between them. This will increase the possibility to extract the seismogenic variations, being mostly local, at the background of the variations of other nature, being mostly enough spacious or even global. Taking into account the present and predictable reduction of the expenses for space scientific research, it would be extremely important to realize such a multi-point mission using the cheapest carriers - nanosatellites, especially cubesats. The analysis of both aspects of this problem - FWC and AGW mechanisms validation and the availability of miniaturized but enough sensitive scientific instrumentation, able to operate onboard cubesats, is made in the report. It shows that the scientific payload creation to realize the given task with the cubesats swarm is possible, including mini-thrusters able realizing the cubesats maneuvers on the orbit to control the distance between satellites. This allows us to come to conclusion that the realization of the cubesat project dedicated to the further study of important problem - detection of EQ precursors from space - may be put into practice at the present step of space science and technology development. Both necessary conditions - existence of scientific and experimental substantiation and of corresponding nanosatellite technology - are fulfilled. These works were partially supported by SSAU Contract No 1-16/12 and EC Framework 7 funded project 312993.

Korepanov, Valery; Lappas, Vaios


Nicotiana benthamiana as a Production Platform for Artemisinin Precursors  

PubMed Central

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-?-diglucoside. This compound accumulated to 39.5 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

van Herpen, Teun W. J. M.; Cankar, Katarina; Nogueira, Marilise; Bosch, Dirk; Bouwmeester, Harro J.; Beekwilder, Jules



Precursor events and self-organization leading to landslide triggering  

NASA Astrophysics Data System (ADS)

Hillslopes often consist of many interacting soil and land-cover elements differing in hydraulic properties and mechanical strength. Intense rainfall events may result in heterogeneous distribution of hydrologic loading and internal weakening leading to local failure and stress redistribution to neighboring intact units. For certain spatial distributions of hydro-mechanical properties and timing of local failure events, ‘local' failure may propagate across the entire system culminating in landslide release (a ‘global' failure). Such ‘global' event is often preceded by numerous small precursor events (local failures) that theoretically may contain statistical information regarding imminent ‘global' failure and thus could provide certain early warning. We model the system and precursor events by combining concepts of Self-Organized Criticality (SOC) and Fiber Bundle Models (FBM) in a physically-based hydro-mechanical framework. The model consists of hexagonal soil columns connected by fiber bundles at their base and between adjacent elements. Fiber bundles represent mechanical bonds made of numerous connections (fibers) representing friction, roots, cementing agents, water bridges and alike that impart soil strength. Hydrological pathways and load distribution are simulated enabling updating of stresses on fiber bundles. When a bundle fails at element base, stress is redistributed to adjacent connected elements which may initiate a cascade of failures similar to other SOC models (e.g. sand pile model). Increasing hydro-mechanical loads during a rainfall event results in gradual small local fiber failures whose statistics follow a power-law with exponent depending on proximity to global failure. Such state-dependent precursor event statistics could provide a physical basis for field monitoring networks for early warning and hazard prediction. Additionally, the SOC concepts provide a simple framework for landslide susceptibility mapping in space and time and may provide input for subsequent debris flow routing models.

Lehmann, Peter; Or, Dani



Prediction of gene network models in limb muscle precursors.  


The ventrolateral dermomyotome gives rise to all muscles of the limbs through the delamination and migration of cells into the limb buds. These cells proliferate and form myoblasts, withdraw from the cell cycle and become terminally differentiated. The myogenic lineage colonizes pre-patterned regions to form muscle anlagen as muscle fibers are assembled. The regulatory mechanisms that control the later steps of this myogenic program are not well understood. The homeodomain transcription factor Pitx2 is expressed in the muscle lineage from the migration of precursors to adult muscle. Ablation of Pitx2 results in distortion, rather than loss, of limb muscle anlagen, suggesting that its function becomes critical during the colonization of, and/or fiber assembly in, the anlagen. Gene expression arrays were used to identify changes in gene expression in flow-sorted migratory muscle precursors, labeled by Lbx1(EGFP), which resulted from the loss of Pitx2. Target genes of Pitx2 were clustered using the "David Bioinformatics Functional Annotation Tool" to bin genes according to enrichment of gene ontology keywords. This provided a way to both narrow the target genes and identify potential gene families regulated by Pitx2. Representative target genes in the most enriched bins were analyzed for the presence and evolutionary conservation of Pitx2 consensus binding sequence, TAATCY, on the -20kb, intronic, and coding regions of the genes. Fifteen Pitx2 target genes were selected based on the above analysis and were identified as having functions involving cytoskeleton organization, tissue specification, and transcription factors. Data from these studies suggest that Pitx2 acts to regulate cell motility and expression of muscle specific genes in the muscle precursors during forelimb muscle development. This work provides a framework to develop the gene network leading to skeletal muscle development, growth and regeneration. PMID:22917675

Campbell, Adam L; Eng, Diana; Gross, Michael K; Kioussi, Chrissa



Accident Precursor Analysis and Management: Reducing Technological Risk Through Diligence  

NASA Technical Reports Server (NTRS)

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.

Phimister, James R. (Editor); Bier, Vicki M. (Editor); Kunreuther, Howard C. (Editor)



Fine-grained precursors dominate the micrometeorite flux  

NASA Astrophysics Data System (ADS)

We optically classified 5682 micrometeorites (MMs) from the 2000 South Pole collection into textural classes, imaged 2458 of these MMs with a scanning electron microscope, and made 200 elemental and eight isotopic measurements on those with unusual textures or relict phases. As textures provide information on both degree of heating and composition of MMs, we developed textural sequences that illustrate how fine-grained, coarse-grained, and single mineral MMs change with increased heating. We used this information to determine the percentage of matrix dominated to mineral dominated precursor materials (precursors) that produced the MMs. We find that at least 75% of the MMs in the collection derived from fine-grained precursors with compositions similar to CI and CM meteorites and consistent with dynamical models that indicate 85% of the mass influx of small particles to Earth comes from Jupiter family comets. A lower limit for ordinary chondrites is estimated at 2-8% based on MMs that contain Na-bearing plagioclase relicts. Less than 1% of the MMs have achondritic compositions, CAI components, or recognizable chondrules. Single mineral MMs often have magnetite zones around their peripheries. We measured their isotopic compositions to determine if the magnetite zones demarcate the volume affected by atmospheric exchange during entry heating. Because we see little gradient in isotopic composition in the olivines, we conclude that the magnetites are a visual marker that allows us to select and analyze areas not affected by atmospheric exchange. Similar magnetite zones are seen in some olivine and pyroxene relict grains contained within MMs.

Taylor, Susan; Matrajt, Graciela; Guan, Yunbin



Radiative precursors driven by converging blast waves in noble gases  

NASA Astrophysics Data System (ADS)

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-1 blast waves through gases of densities of the order 10-5 g cm-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.

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.; de Grouchy, P.; Skidmore, J.; Suttle, L.; Bennett, M.; Niasse, N. P. L.; Williams, R. J. R.; Blesener, K.; Atoyan, L.; Cahill, A.; Hoyt, C.; Potter, W.; Rosenberg, E.; Schrafel, P.; Kusse, B.



Radiative precursors driven by converging blast waves in noble gases  

SciTech Connect

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.

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. [Blackett Laboratory, Imperial College London SW7 2BW (United Kingdom)] [Blackett Laboratory, Imperial College London SW7 2BW (United Kingdom); Williams, R. J. R. [Atomic Weapons Establishment, Aldermaston RG7 4PR (United Kingdom)] [Atomic Weapons Establishment, Aldermaston RG7 4PR (United Kingdom); Blesener, K.; Atoyan, L.; Cahill, A.; Hoyt, C.; Potter, W. [Laboratory of Plasma Studies, Cornell University, Ithaca, New York 14853 (United States)] [Laboratory of Plasma Studies, Cornell University, Ithaca, New York 14853 (United States); and others



Application of a Global Proteomic Approach to Archival Precursor Lesions: Deleted in Malignant Brain Tumors 1 and Tissue Transglutaminase 2 Are Upregulated in Pancreatic Cancer Precursors  

Microsoft Academic Search

Background: Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset of invasive cancer. Biomarker discovery in precursor lesions has been hampered by the ready availability of fresh specimens, and

Wang Cheung; Marlene M. Darfler; Hector Alvarez; Brian L. Hood; Thomas P. Conrads; Nils Habbe; David B. Krizman; Jan Mollenhauer; Georg Feldmann; Anirban Maitra



Biosynthesis of Riboflavine in Corynebacterium Species: the Purine Precursor  

PubMed Central

Corynebacterium species lacks the ability to convert either xanthine or guanine to adenine. This defect and the use of the purine nucleoside antibiotic decoyinine, which blocks the conversion of xanthosine monophosphate ? guanosine monophosphate, permit an experimental design in which the interconversion of purines is largely prevented. Cultures of this organism were grown in the presence of decoyinine and various purine supplements. Data obtained by comparing the radioactivity incorporated from guanine-2-14C or xanthine-2-14C into bacterial guanine, xanthine, and riboflavine indicate that guanine or a close derivative of guanine is the purine precursor of riboflavine. PMID:5788699

Baugh, Charles M.; Krumdieck, Carlos L.



Lunar Precursor Robotic Program: A Robotic Focus To The Vision  

NASA Technical Reports Server (NTRS)

In April 2006, NASA, with help from the commercial and international communities, began developing a global Lunar Exploration Strategy. These activities resulted in themes that expanded on why we should return to the Moon and objectives that identify what we should do when we get there. NASA used these results to develop a Lunar Architecture designed to achieve the subset of the global Lunar Exploration Strategy objectives that fit within NASA's scope. A component of this architecture is the Lunar Precursor Robotic Program. This Program, anticipated to consist of both lunar orbiters and landers, is intended to meet many of NASA's lunar exploration objectives.

French, Raymond A.; Nall, Mark E.



CVD Of Thin Films From Single Organometallic Precursors  

NASA Technical Reports Server (NTRS)

Method of forming thin inorganic films involves chemical vapor deposition (CVD) from single organometallic precursors. No toxic constituents, minimizes impurities, and yields films having substantially uniform crystal structure and composition. Especially suitable for depositing high-quality passivating or buffer layers of GaS on GaAs semiconductor substrates. Also applicable to formation of high-quality films for purposes other than buffering or passivation, and to different materials in which another element from same group in periodic table of elements substituted for all or portion of each element in GaS/GaAs system.

Hepp, Aloysius F.; Barron, Andrew R.; Power, Michael B.; Macinnes, Andrew N.; Jenkins, Phillip P.



Gelcasting polymeric precursors for producing net-shaped graphites  


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.

Klett, James W. (Knoxville, TN); Janney, Mark A. (Knoxville, TN)



Vulvar cancer and the need for awareness of precursor lesions.  


Vulvar cancer continues to rise in incidence. In the absence of screening, attempts to reduce this cancer must focus on recognizing precursor lesions, namely, lichen sclerosus and vulvar intraepithelial neoplasia (VIN). The steep rise in human papillomavirus-repeated VIN will fall after the introduction of vaccination against human papillomavirus; in the meantime, those patients with VIN must be treated and then reviewed carefully and frequently. Lichen sclerosus has a 3% to 5% risk of progressing to vulvar cancer. Recommendations about which patients require referral to and follow-up by specialists/specialist clinics are given. PMID:19387133

Maclean, Allan B; Jones, Ronald W; Scurry, James; Neill, Sallie



Beryllium-10 in australasian tektites: evidence for a sedimentary precursor.  


Each of seven Australasian tektites contains about 1 x l0(8) atoms of beryllium-10 (half-life, 1.53 x 10(6) 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. PMID:17771035

Pal, D K; Tuniz, C; Moniot, R K; Kruse, T H; Herzog, G F



Beryllium-10 in Australasian tektites: evidence for a sedimentary precursor  

SciTech Connect

Each of seven Australasian tektites contains about 1 x 10/sup 8/ atoms of beryllium-10 (half-life, 1.53 x 10/sup 6/ 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.

Pal, D.K.; Tuniz, C.; Moniot, R.K.; Kruse, T.H.; Herzog, G.F.



Epigenetic mechanisms regulating differentiation of neural stem/precursor cells.  


Differentiation of neural stem/precursor cells (NS/PCs) into neurons, astrocytes and oligodendrocytes during mammalian brain development is a carefully controlled and timed event. Increasing evidences suggest that epigenetic regulation is necessary to drive this. Here, we provide an overview of the epigenetic mechanisms involved in the developing mammalian embryonic forebrain. Histone methylation is a key factor but other epigenetic factors such as DNA methylation and noncoding RNAs also partake during fate determination. As numerous epigenetic modifications have been identified, future studies on timing and regional specificity of these modifications will further deepen our understanding of how intrinsic and extrinsic mechanisms participate together to precisely control brain development. PMID:25531257

Adefuin, Aliya Mari D; Kimura, Ayaka; Noguchi, Hirofumi; Nakashima, Kinichi; Namihira, Masakazu



Prediction of MicroRNA Precursors Using Parsimonious Feature Sets  

PubMed Central

MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate gene expression through base pairing with messenger RNAs. Due to the interest in studying miRNA dysregulation in disease and limits of validated miRNA references, identification of novel miRNAs is a critical task. The performance of different models to predict novel miRNAs varies with the features chosen as predictors. However, no study has systematically compared published feature sets. We constructed a comprehensive feature set using the minimum free energy of the secondary structure of precursor miRNAs, a set of nucleotide-structure triplets, and additional extracted sequence and structure characteristics. We then compared the predictive value of our comprehensive feature set to those from three previously published studies, using logistic regression and random forest classifiers. We found that classifiers containing as few as seven highly predictive features are able to predict novel precursor miRNAs as well as classifiers that use larger feature sets. In a real data set, our method correctly identified the holdout miRNAs relevant to renal cancer. PMID:25392687

Stepanowsky, Petra; Levy, Eric; Kim, Jihoon; Jiang, Xiaoqian; Ohno-Machado, Lucila



Flow-Induced Crystallization Precursor Structure in Entangled Polymer Melt.  

NASA Astrophysics Data System (ADS)

Flow-induced crystallization has long been an important subject in polymer processing. Varying processing conditions can produce different morphologies, which lead to different properties. Recent studies indicated that the final morphology is in fact dictated by the initial formation of crystallization precursor structures (i.e., shish kebabs) under flow. In this talk, factors that affect the shish-kebab formation in entangled polymer melts are systematically reviewed, including the concept of coil-stretch transition, chain dynamics, critical orientation molecular weight, phase transition during shish and kebab formations. In particular, recent experimental results from in-situ rheo-X-ray studies and ex-situ microscopic examinations have been presented to illustrate several new findings of flow-induced shish-kebab structures in polymer melts. (1) The shish entity consists of stretched chains (or chain segments) that can be in the amorphous, mesomorphic or crystalline state. (2) The kebab entity mainly arises from the crystallization of coiled chains (or chain segments), which seems to follow a diffusion-control growth process. (3) A shish-kebab structure with multiple shish was seen in the ultra-high molecular weight polyethylene (UHMWPE) precursor. Based on the above results and recent simulation work from other laboratories, a modified molecular mechanism for the shish-kebab formation in entangled melt is presented.

Hsiao, Benjamin



Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors  

PubMed Central

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 ? (PDGFR?). PDGFR?-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFR?+-derived cells abolished FDC, indicating that FDC originate from PDGFR?+ cells. Lymphotoxin-?-overexpressing prion protein (PrP)+ kidneys developed PrP+ FDC after transplantation into PrP mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFR?+ stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin ? receptor (LT?R) kidney capsules, differentiated into Mfge8+CD21/35+ Fc?RII?+PrP+ FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFR?+ 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

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



Over-the-Horizon Anomalous VHF Propagation and Earthquake Precursors  

NASA Astrophysics Data System (ADS)

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.

Devi, M.; Barbara, A. K.; Ruzhin, Ya. Yu.; Hayakawa, M.



An Accident Precursor Analysis Process Tailored for NASA Space Systems  

NASA Technical Reports Server (NTRS)

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.

Groen, Frank; Stamatelatos, Michael; Dezfuli, Homayoon; Maggio, Gaspare



Novel drug delivery strategies for porphyrins and porphyrin precursors  

NASA Astrophysics Data System (ADS)

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.

Morrow, D. I. J.; Donnelly, R. F.



Siloxane and silsesquioxane molecules—Precursors for silicate materials  

NASA Astrophysics Data System (ADS)

Preparation of ceramics by sol-gel method has been known for many years, but recently it has been developed as a method for the synthesis of nanostructural ceramic materials. Hydrolytic polycondensation of simple molecules [e.g. most widely used tetraethoxysilane (TEOS)] leads to xerogel materials that can contain macromolecules of distinct random, ladder and cage or partial cage structure. In order to obtain well-defined silsesquioxanes it is preferred to start the process with more complex molecules, bringing in a specific framework that can govern the structure of the product. In the presented work alkoxy derivatives of cyclosiloxanes and polysiloxanes as well as a hydride derivative of octahedral silsequioxane (T 8H) were applied as precursors in the process of hydrolytic polycondensation. Depending on the reaction conditions, silsesquioxane macromolecules or silica material of ordered structure were obtained. We have prepared mesoporous organiosilica materials without using any template or surfactant whatsoever. The meso-pores are created due to the unique structure of initial oligosiloxane or silsequioxane molecules and the specific interactions in the used catalyst/solvent system. In the case of octasilsesquioxane precursor, the condensation process gives directly mesoporous silica material. Dried polysilsesquioxanes were heated at the temperature of 600 °C in argon or air atmosphere (pyrolysis or ceramization). In the atmosphere of argon SiC xO y glass materials were obtained.

Handke, M.; Kowalewska, A.



Phosphorylation of murine mammary tumor virus precursor polypeptides.  

PubMed Central

Phosphorylation of the murine mammary tumor virus (MuMTV) structural proteins was studied in an MuMTV-infected epithelial cell line derived from a BALB/cf C3H mouse mammary tumor. Immunoprecipitation of 32P-labeled cell extracts with monospecific anti-p27 serum revealed that phosphorylation occurred at the stage of the core-protein polyprotein precursor prp75. Two forms of phosphorylated prp75 were found: one migrating with an apparent molecular weight of 80,000, and the other with a molecular weight of 76,000. The 80,000-molecular-weight species was found to be the most heavily phosphorylated. In addition, a relatively stable phosphorylated processing intermediate of 34,000 molecular weight was observed as well. Tryptic peptide mapping analysis of the 32P-labeled viral proteins indicated a precursor product relationship between the intracellular phosphorylated, high-molecular-weight peptides and the mature MuMTV phosphoproteins p23 and p27. Phosphopeptide analysis also suggested that phosphorylation of the viral proteins occurred in discrete steps and that the attached phosphate groups were conserved throughout the processing steps. Images PMID:225520

Racevskis, J; Sarkar, N H



Ceramic fibers from SI-B-C polymer precursors  

SciTech Connect

Non-oxide ceramics such as silicon carbide (SiC), silicon nitride (Si[sub 3]N[sub 4]), and silicon borides (SiB[sub 4], SiB[sub 6]) have thermal stability, oxidation resistance, hardness, and varied electrical properties. All these materials can be prepared in a fiber form from a suitable polymer precursor. Silicon carbide fiber (Nicalon), for example, has been successfully produced by the polymer-pyrolysis route, and is presently available from Nippon Carbon. More recently, other fibers have been made available, such as the silicon nitride fiber from Dow Corning Co. and Tyranno fiber from Textron Specialty Materials. The above mentioned fibers, when tested over a temperature range from 25[degrees]C to 1400[degrees]C, experience degradation at elevated temperatures. Past work in ceramic materials has shown that the strength of ceramics containing both carbides and borides is sustained at elevated temperatures, with minimum oxidation. The work presented here describes the formation of ceramic fibers containing both elements, boron and silicon, prepared via the polymer precursor route previously reported by the authors, and discusses the fiber mechanical properties that are retained over the temperature range studied. 18 refs., 6 figs., 1 tab.

Riccitiello, S.R. (NASA-Ames Research Center, Moffett Field, CA (United States)); Hsu, M.S.; Chen, T.S. (HC Chem Research Service Corp., San Jose, CA (United States))




SciTech Connect

In shock precursors populated by accelerated cosmic rays (CRs), the CR return current instability is believed to significantly enhance the pre-shock perturbations of magnetic field. We have obtained fully nonlinear exact ideal MHD solutions supported by the CR return current. The solutions occur as localized spikes of circularly polarized Alfven envelopes (solitons or breathers). As the conventional (undriven) solitons, the obtained magnetic spikes propagate at a speed C proportional to their amplitude, C=C{sub A}B{sub max}/{radical}2B{sub 0}. The sufficiently strong solitons run thus ahead of the main shock and stand in the precursor, being supported by the return current. This property of the nonlinear solutions is strikingly different from the linear theory that predicts non-propagating (that is, convected downstream) circularly polarized waves. The nonlinear solutions may come either in isolated pulses (solitons) or in soliton-trains (cnoidal waves). The morphological similarity of such quasi-periodic soliton chains with recently observed X-ray stripes in the Tycho supernova remnant (SNR) is briefly discussed. The magnetic field amplification determined by the suggested saturation process is obtained as a function of decreasing SNR blast wave velocity during its evolution from the ejecta dominated to the Sedov-Taylor stage.

Malkov, M. A.; Diamond, P. H. [CASS and Department of Physics, University of California, San Diego, La Jolla, CA 92093 (United States); Sagdeev, R. Z., E-mail: [Department of Physics, University of Maryland, College Park, MD 20742-3280 (United States)



MOCVD of aluminium oxide films using aluminium ?-diketonates as precursors  

NASA Astrophysics Data System (ADS)

Deposition of Al203 coatings by CVD is of importance because they are often used as abrading material in cemented carbide cutting tools. The conventionally used CVD process for Al203 involves the corrosive reactant AICl3. In this paper, we report on the thermal characterisation of the metalorganic precursors namely aluminium tris-tetramethyl-heptanedionate [ Al(thd)3] and aluminium tris-acetylacetonate [ Al(acac)3] and their application to the CVD of Al203 films. Crystalline A1203 films were deposited by MOCVD at low temperatures by the pyrolysis of Al(thd)3 and AI(acac)3. The films were deposited on a TiN-coated tungsten carbide (TiN/WC) and Si(100) substrates in the temperature range 500-1100 °C. The as-deposited films were characterised by x-ray diffraction, optical microscopy, scanning and transmission electron microscopy, Auger electron spectroscopy. The observed crystallinity of films grown at low temperatures, their microstructure, and composition may be interpreted in terms of a growth process that involves the melting of the metalorganic precursor on the hot growth surface.

Devi, A.; Shivashankar, S. A.; Samuelson, A. G.



Solar Cycle Prediction Using Precursors and Flux Transport Models  

NASA Astrophysics Data System (ADS)

We study the origin of the predictive skill of some methods to forecast the strength of solar activity cycles. A simple flux transport model for the azimuthally averaged radial magnetic field at the solar surface is used, which contains a source term describing the emergence of new flux based on observational sunspot data. We consider the magnetic flux diffusing over the equator as a predictor, since this quantity is directly related to the global dipole field from which a Babcock-Leighton dynamo generates the toroidal field for the next activity cycle. If the source is represented schematically by a narrow activity belt drifting with constant speed over a fixed range of latitudes between activity minima, our predictor shows considerable predictive skill, with correlation coefficients up to 0.95 for past cycles. However, the predictive skill is completely lost when the actually observed emergence latitudes are used. This result originates from the fact that the precursor amplitude is determined by the sunspot activity a few years before solar minimum. Since stronger cycles tend to rise faster to their maximum activity (known as the Waldmeier effect), the temporal overlapping of cycles leads to a shift of the minimum epochs that depends on the strength of the following cycle. This information is picked up by precursor methods and also by our flux transport model with a schematic source. Therefore, their predictive skill does not require a memory, i.e., a physical connection between the surface manifestations of subsequent activity cycles.

Cameron, R.; Schüssler, M.



Malignant melanoma in a black child: predisposing precursors and management.  

PubMed Central

Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child. Primary neoplastic transformation and metastatic spread were suggested by the appearance of multiple swellings over the "garment" precursor nevus at the posterior trunk, multiple ipsilateral axillary nodal enlargement, and fresh occipital swellings postadmission. Smaller-sized hyperpigmented lesions with irregular, nonlobulated, and frequently hairy surfaces were also discernible over the upper and lower extremities, but the face, anterior trunk, and mucosal surfaces were relatively spared. A diagnosis of MM was confirmed by the subsequent histopathologic findings from the fine-needle aspirate and biopsy specimens. Chemotherapy was initiated but was truncated shortly after by parent-pressured discharge. Despite the rarity of MM in a tropical African setting where management options are few, the current case underscores the need for a high clinical index of diagnostic suspicion, an early pursuit of investigative confirmation, and prophylactic excision in children with the predisposing skin lesions, like congenital giant hairy nevus. An expounded discourse of the possible precursors and management options of MM is provided. We emphasize the need for institutional cost subsidy for anticancer care in tropical children. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:15540891

Adedoyin, Olanrewaju T.; Johnson, Abdul-Wahab B. R.; Ojuawo, Ayodele I.; Afolayan, Enoch A. O.; Adeniji, Kayode A.



Assembly and architecture of precursor nodes during fission yeast cytokinesis  

PubMed Central

The contractile ring is essential for cytokinesis in most fungal and animal cells. In fission yeast, cytokinesis nodes are precursors of the contractile ring and mark the future cleavage site. However, their assembly and architecture have not been well described. We found that nodes are assembled stoichiometrically in a hierarchical order with two modules linked by the positional marker anillin Mid1. Mid1 first recruits Cdc4 and IQGAP Rng2 to form module I. Rng2 subsequently recruits the myosin-II subunits Myo2 and Rlc1. Mid1 then independently recruits the F-BAR protein Cdc15 to form module II. Mid1, Rng2, Cdc4, and Cdc15 are stable node components that accumulate close to the plasma membrane. Both modules recruit the formin Cdc12 to nucleate actin filaments. Myo2 heads point into the cell interior, where they efficiently capture actin filaments to condense nodes into the contractile ring. Collectively, our work characterizing the assembly and architecture of precursor nodes defines important steps and molecular players for contractile ring assembly. PMID:21422229

Laporte, Damien; Coffman, Valerie C.; Lee, I-Ju



NeuroPID: a classifier of neuropeptide precursors.  


Neuropeptides (NPs) are short secreted peptides produced in neurons. NPs act by activating signaling cascades governing broad functions such as metabolism, sensation and behavior throughout the animal kingdom. NPs are the products of multistep processing of longer proteins, the NP precursors (NPPs). We present NeuroPID (Neuropeptide Precursor Identifier), an online machine-learning tool that identifies metazoan NPPs. NeuroPID was trained on 1418 NPPs annotated as such by UniProtKB. A large number of sequence-based features were extracted for each sequence with the goal of capturing the biophysical and informational-statistical properties that distinguish NPPs from other proteins. Training several machine-learning models, including support vector machines and ensemble decision trees, led to high accuracy (89-94%) and precision (90-93%) in cross-validation tests. For inputs of thousands of unseen sequences, the tool provides a ranked list of high quality predictions based on the results of four machine-learning classifiers. The output reveals many uncharacterized NPPs and secreted cell modulators that are rich in potential cleavage sites. NeuroPID is a discovery and a prediction tool that can be used to identify NPPs from unannotated transcriptomes and mass spectrometry experiments. NeuroPID predicted sequences are attractive targets for investigating behavior, physiology and cell modulation. The NeuroPID web tool is available at http:// PMID:24792159

Karsenty, Solange; Rappoport, Nadav; Ofer, Dan; Zair, Adva; Linial, Michal



Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors formed by such methods  


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.

Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.



The presence of modifiable residues in the core peptide part of precursor nisin is not crucial for precursor nisin interactions with NisB- and NisC.  


Precursor nisin is a model posttranslationally modified precursor lantibiotic that can be structurally divided into a leader peptide sequence and a modifiable core peptide part. The nisin core peptide clearly plays an important role in the precursor nisin-nisin modification enzymes interactions, since it has previously been shown that the construct containing only the nisin leader sequence is not sufficient to pull-down the nisin modification enzymes NisB and NisC. Serines and threonines in the core peptide part are the residues that NisB specifically dehydrates, and cysteines are the residues that NisC stereospecifically couples to the dehydrated amino acids. Here, we demonstrate that increasing the number of negatively charged residues in the core peptide part of precursor nisin, which are absent in wild-type nisin, does not abolish binding of precursor nisin to the modification enzymes NisB and NisC, but dramatically decreases the antimicrobial potency of these nisin mutants. An unnatural precursor nisin variant lacking all serines and threonines in the core peptide part and an unnatural precursor nisin variant lacking all cysteines in the core peptide part still bind the nisin modification enzymes NisB and NisC, suggesting that these residues are not essential for direct interactions with the nisin modification enzymes NisB and NisC. These results are important for lantibiotic engineering studies. PMID:24040355

Khusainov, Rustem; Kuipers, Oscar P



Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system.  


Oligodendrocyte precursor cells, which persist in the adult central nervous system, are the main source of central nervous system remyelinating cells. In multiple sclerosis, some demyelinated plaques exhibit an oligodendroglial depopulation, raising the hypothesis of impaired oligodendrocyte precursor cell recruitment. Developmental studies identified semaphorins 3A and 3F as repulsive and attractive guidance cues for oligodendrocyte precursor cells, respectively. We previously reported their increased expression in experimental demyelination and in multiple sclerosis. Here, we show that adult oligodendrocyte precursor cells, like their embryonic counterparts, express class 3 semaphorin receptors, neuropilins and plexins and that neuropilin expression increases after demyelination. Using gain and loss of function experiments in an adult murine demyelination model, we demonstrate that semaphorin 3A impairs oligodendrocyte precursor cell recruitment to the demyelinated area. In contrast, semaphorin 3F overexpression accelerates not only oligodendrocyte precursor cell recruitment, but also remyelination rate. These data open new avenues to understand remyelination failure and promote repair in multiple sclerosis. PMID:21421691

Piaton, Gabrièle; Aigrot, Marie-Stéphane; Williams, Anna; Moyon, Sarah; Tepavcevic, Vanja; Moutkine, Imane; Gras, Julien; Matho, Katherine S; Schmitt, Alain; Soellner, Heidi; Huber, Andrea B; Ravassard, Philippe; Lubetzki, Catherine



Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis  

PubMed Central

We have compared the sensitivity of clonogenic interleukin 7 (IL-7)- dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis- inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells. PMID:8195708



Consideration of formation process for the nuclei on precursor  

NASA Astrophysics Data System (ADS)

The very isotropic microwave background and the Hubble expansion indicate that the universe has evolved from an earlier state of high temperature and density that can be reasonably well described by Friedman-Lemaitre-Robertson-Walker cosmological models. The nuclear evolution of non-degenerate matter expanding from very high temperature was studied in detail for various values of the expansion rate and of the proton-neutron abundance difference and baryon density[1,2,3]. In this calculation, many nuclear reactions were included, and its results suggested important reaction process for the evolution of nuclear abundances. 3He and 4He are very important elements in these nuclear reactions as the primordial nucleosynthesis. Microscopic study for few body system is one main topic in nuclear theoretical physics. In this field, very accurate calculations are available by using the Faddeev equations[4]. Recently, many data for pd, p-3He and d-3He have been obtained including polarized observables. Model calculations for systems including 3He and 4He (for example, d + 3He -> p + 4He) are carried out using the Faddeev equations based on the meson exchange models[4]. This model reproduces well the empirical phase shifts which are determined by so-called phase-shift analyses using all of available scattering data measured at various laboratories around the world[5,6,7]. Constructions of models for the nuclear reactions including 3He and 4He will give important information for calculations of the primordial nucleosynthesis after big-ban. The calculations are carried out until the sum of the abundances at each mass number ceases to change. Various different set of initial conditions for the baryon mass density, the expansion rate and the neutron-proton ratio are used. Dusts kept in precursor asteroid nebular form precursor asteroid, then, formations of planet start [8]. Possible values of parameters in the initial conditions for theoretical calculations will be searched considering an information from precursor asteroid References: {[1]} R. V. Wagoner, W. A. Fowler and F. Hoyle (1967), Astrophys. J. 148, 3. {[2]} R. V. Wagoner. (1969), Astrophys. J. 162, 247. [3] R. V. Wagoner (1973), Astrophys. J. 179, 343. [4] For example, S. Gojyuki and S. Oryu (2003), Mod. Phys. Lett. A18, 302. [5] Y. Yoshino, V. Limkaisang, J. Nagata, H. Yoshino and M. Matsuda (2000), Prog. Theor. Phys. 103, 107. [6] H. Yoshino, J. Nagata, V. Limkaisang, Y. Yoshino, M. Matsuda (2001), Nucl. Phys. A684, 615c. [7] H. Yoshino, H. Kazuo, M. Matsuda, J. Nagata, (2003), Mod. Phys. Lett. A18, 444. [8] Hayashi, C. et. al., 1985, Protostars and Planets, Univ. of Arizona Press, pp. 1100.

Nagata, J.; Okamoto, M.



Improved anthraquinone accumulation in cell cultures of Cinchona `Robusta' by feeding of biosynthetic precursors and inhibitors  

Microsoft Academic Search

The effects of feeding of biosynthetic precursors and pathway specific inhibitors on anthraquinone (AQ) accumulation in fungal elicited cell cultures of Cinchona`Robusta' were studied. Addition of glyceraldehyde (1 mM), the initial precursor in the methyl-d-erythritol 4-phosphate (MEP) pathway, did not increase AQ accumulation, suggesting that the endogenous level of this precursor is not a limiting factor of AQ flux. It

Ying-Shan Han; Robert van der Heijden; Robert Verpoorte



Synthesis and studies of growth kinetics of monodispersed iron oxide nanoparticles using ferrocene as novel precursor  

NASA Astrophysics Data System (ADS)

We have used ferrocene and paraffin wax as novel precursor and solvent for the growth of iron oxide nanoparticles. The proposed method of growth has several advantages over existing methods of growth using iron pentacarbonyl a precursor. Highly crystalline and monodispersed particles are obtained which assemble in two- and three-dimensional hexagonal closed packed superlattices. Growth kinetics has been studied by varying concentration of the precursor and time of growth. A phenomenological model has been proposed to explain the growth kinetics.

Bhalerao, G. M.; Sinha, A. K.; Srivastava, Himanshu; Srivastava, A. K.



Structural transformation with milling on sol-gel precursor for BaM hexaferrite  

Microsoft Academic Search

The structural modification upon milling in an intermediate step precursor of the sol-gel method for BaFe12O19 hexaferrite BaM production is discussed. The milling of the precursor diminishes the powder particle size, leads to a more homogeneous matrix and induces a solid-state transformation, from gamma-Fe2O3 to alpha-Fe2O3. The induced modifications of the precursors change the magnetic and structural properties of the

E. Estevez Rams; R. Martinez Garcia; E. Reguera; H. Montiel Sanchez; H. Y. Madeira



Regulation of macrophage and dendritic cell responses by their lineage precursors  

PubMed Central

Tissue macrophages and dendritic cells derive from hematopoietic stem cells, which exist in the bone marrow and generate intermediate precursor populations with increasingly restricted lineage potentials. There exists several precursors committed to the macrophage and dendritic cell lineages; these cells exhibit distinct tropism and function and respond differentially in pathophysiologic conditions. In this review, we consider experimental contexts in which macrophage and dendritic cell responses in tissue are not only dictated by the local environment, but also by the quantity and quality of newly recruited lineage precursor cells. Consequently, we discuss whether therapeutic control of macrophage and dendritic cell responses in tissue may be achieved through manipulation of their lineage precursors. PMID:22433183

Cortez-Retamozo, Virna; Etzrodt, Martin; Pittet, Mikael J.



Structural transformation with milling on sol-gel precursor for BaM hexaferrite  

NASA Astrophysics Data System (ADS)

The structural modification upon milling in an intermediate step precursor of the sol-gel method for BaFe12O19 hexaferrite BaM production is discussed. The milling of the precursor diminishes the powder particle size, leads to a more homogeneous matrix and induces a solid-state transformation, from ?-Fe2O3 to ?-Fe2O3. The induced modifications of the precursors change the magnetic and structural properties of the final BaM hexaferrite compared to the BaM obtained from the non-milled precursor.

Estevez Rams, E.; Martinez Garcia, R.; Reguera, E.; Montiel Sanchez, H.; Madeira, H. Y.



Formation of perfluorinated surfactants from precursors by indigenous microorganisms in groundwater.  


The formation of perfluorinated surfactants (PFSs) from their precursors in waters is of concern. In this study, the formation of PFSs through biodegradation of precursors was measured in incubation tests. Indigenous microorganisms in groundwater were able to biodegrade perfluorooctane sulfonamide (FOSA) to yield perfluorooctane sulfonate (PFOS). The addition of nutrients and soil promoted the formation. A 42-d incubation test using sources of groundwater recharge showed that PFOS, perfluorooctanoate, and perfluorononanoate were significantly and remarkably (?1.5×) formed from precursors in street runoff through biodegradation, but not in rainwater or wastewater effluent. Significant formation of PFSs from precursors in street runoff was observed. PMID:23746363

Murakami, Michio; Nishikoori, Hiroshi; Sakai, Hiroshi; Oguma, Kumiko; Takada, Hideshige; Takizawa, Satoshi



The synthesis of ?-alkoxy and ?-aminostannanes as precursors to Novel Chromium Fischer Carbenes.  

E-print Network

??The present study involves the use of main group organometallics: organostannanes and organolithiums as precursors to chromium Fischer carbene complexes. Fischer carbenes are well stabilized… (more)

Meyer, Annalene



Sensitivity of ozone production rate to ozone precursors  

NASA Astrophysics Data System (ADS)

The photochemical equations describing O3 formation in the lower troposphere contain 2 major sink terms for free radicals; combination reactions and reactions with NOx. Knowing the fraction of radicals removed by reactions with NOx, termed LN/Q, allows one to predict the sensitivity of O3 production to NO and VOCs. We derive an analytic formula that gives LN/Q in terms of readily measured O3 precursors and test this formula using constrained steady state calculations based on field observations gathered in Phoenix, Arizona. The formula quantifies well-known results regarding the effects of dilution, oxidation, and the production of oxidants on the transition from VOC to NOx sensitive behavior as an air parcel is advected away from an urban source.

Kleinman, Lawrence I.; Daum, Peter H.; Lee, Yin-Nan; Nunnermacker, Linda J.; Springston, Stephen R.; Weinstein-Lloyd, Judith; Rudolph, Jochen


Natural Modulators of Amyloid-Beta Precursor Protein Processing  

PubMed Central

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the primary cause of dementia, with no cure currently available. The pathogenesis of AD is believed to be primarily driven by A?, the principal component of senile plaques. A? is an ~4 kDa peptide generated from the amyloid-? precursor protein (APP) through proteolytic secretases. Natural products, particularly those utilized in traditional Chinese medicine (TCM), have a long history alleviating common clinical disorders, including dementia. However, the cell/molecular pathways mediated by these natural products are largely unknown until recently when the underlying molecular mechanisms of the disorders begin to be elucidated. Here, the mechanisms with which natural products modulate the pathogenesis of AD are discussed, in particular, by focusing on their roles in the processing of APP. PMID:22998566

Zhang, Can; Tanzi, Rudolph E.



Finite Element Analysis of Extrusion of Multifilamentary Superconductor Precursor  

SciTech Connect

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.

Peng, X.; Sumption, M.D.; Collings, E.W. [LASM, Department of Materials Science and Engineering, Ohio State University, Columbus, OH, 43210 (United States)



Molecular genetics of B-precursor acute lymphoblastic leukemia  

PubMed Central

B-precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood tumor and the leading cause of cancer-related death in children and young adults. The majority of B-ALL cases are aneuploid or harbor recurring structural chromosomal rearrangements that are important initiating events in leukemogenesis but are insufficient to explain the biology and heterogeneity of disease. Recent studies have used microarrays and sequencing to comprehensively identify all somatic genetic alterations in acute lymphoblastic leukemia (ALL). These studies have identified cryptic or submicroscopic genetic alterations that define new ALL subtypes, cooperate with known chromosomal rearrangements, and influence prognosis. This article reviews these advances, discusses results from ongoing second-generation sequencing studies of ALL, and highlights challenges and opportunities for future genetic profiling approaches. PMID:23023711

Mullighan, Charles G.



Rhamnose biosynthesis in mycoplasmas requires precursor glycans larger than monosaccharide.  


Despite the apparent absence of genes coding for the known pathways for biosynthesis, the monosaccharide rhamnose was detected in the d configuration in Mycoplasma pneumoniae and Mycoplasma pulmonis, and in both the d and l configurations in Mycoplasma arthritidis. Surprisingly, the monosaccharide glucose was not a precursor for rhamnose biosynthesis and was not incorporated at detectable levels in glucose-containing polysaccharides or glycoconjugates. In contrast, carbon atoms from starch, a polymer of glucose, were incorporated into rhamnose in each of the three species examined. When grown in a serum-free medium supplemented with starch, M.?arthritidis synthesized higher levels of rhamnose, with a shift in the relative amounts of the d and l configurations. Our findings suggest the presence of a novel pathway for rhamnose synthesis that is widespread in the genus Mycoplasma. PMID:23826905

Jordan, David S; Daubenspeck, James M; Dybvig, Kevin



Case series of precursor B-cell lymphoblastic lymphoma  

PubMed Central

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon subtype of Non-Hodgkin lymphoma (NHL), accounting for only 0.3% of NHL in adults and less than 10% of all LBL cases. Unlike T-cell LBL, it usually presents with extranodal involvement while sparing the bone marrow (BM). Among the 27 patients with LBL treated in the Asan Medical Center between January 2007 and March 2012, 3 had B-LBL. All had a good performance status and low International Prognostic Index. However, unlike most previously reported cases, the patients had lymphoma in their bone marrow and extranodal sites such as bone and lung. After intensive combination chemotherapy, one patient achieved a complete response and the other 2 patients, a partial response. Our experience suggests that multiple extranodal sites may be involved in B-LBL and BM involvement may not be as infrequent as previously thought. Furthermore, intensive chemotherapy seems to be effective.

Kim, Jin Yong; Om, Sang Yong; Shin, Su-Jin; Kim, Jeong Eun; Yoon, Dok Hyun



Hybrid biosynthesis of roseobacticides from algal and bacterial precursor molecules.  


Roseobacticides regulate the symbiotic relationship between a marine bacterium (Phaeobacter inhibens) and a marine microalga (Emiliania huxleyi). This relationship can be mutualistic, when the algal host provides food for the bacteria and the bacteria produce growth hormones and antibiotics for the algae, or parasitic, when the algae senesce and release p-coumaric acid. The released p-coumaric acid causes the bacteria to synthesize roseobacticides, which are nM-?M toxins for the algae. We examined the biosynthesis of roseobacticides and report that all roseobacticide precursors play critical roles during the mutualist phase of the symbiosis. Roseobacticides are biosynthesized from the algal growth promoter, the major food molecule provided by the algal cells, and the algal senescence signal that initiates the mutualist-to-parasite switch. Thus, molecules that are beneficial during mutualism are diverted to the synthesis of toxins during parasitism. A plausible mechanism for assembling roseobacticides from these molecules is proposed. PMID:25295497

Seyedsayamdost, Mohammad R; Wang, Rurun; Kolter, Roberto; Clardy, Jon



Auditory hair cell precursors immortalized from the mammalian inner ear.  

PubMed Central

Mammalian auditory hair cells are few in number, experimentally inaccessible, and do not proliferate postnatally or in vitro. Immortal cell lines with the potential to differentiate into auditory hair cells would substantially facilitate auditory research, drug development, and the isolation of critical molecules involved in hair cell biology. We have established two conditionally immortal cell lines that express at least five characteristic hair cell markers. These markers are the transcription factor Brn3.1, the alpha 9 subunit of the acetylcholine receptor, the stereociliary protein fimbrin and the myosins VI and VIIA. These hair cell precursors permit functional studies of cochlear genes and i